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Molla MD, Symonds EL, Winter JM, Debie A, Wassie MM. Metabolic risk factors of colorectal cancer: Umbrella review. Crit Rev Oncol Hematol 2024; 204:104502. [PMID: 39245299 DOI: 10.1016/j.critrevonc.2024.104502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/28/2024] [Accepted: 08/29/2024] [Indexed: 09/10/2024] Open
Abstract
BACKGROUND AND AIM The association between metabolic factors and colorectal cancer (CRC) risk is inconclusive. This umbrella review aimed to summarise and describe the association using existing systematic reviews and/or meta-analyses. METHOD Four databases (Medline, Scopus, Web of Science, and Cochrane Library) were searched for systematic reviews and/or meta-analyses of observational studies. Two independent authors extracted data on the summary estimated effect and heterogeneity of studies using I2 from the individual reviews. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) tool was used to evaluate the methodological quality. RESULTS 49 articles were included in this review. Although most included studies were graded with critically low methodological quality (81.6 %), we found a significant positive association between obesity (summary relative risk (SRR) range 1.19-1.49), diabetes mellitus (SRR range 1.20-1.37), hypertension (SRR range 1.07-1.62), metabolic syndrome (SRR range 1.25-1.36), non-alcoholic fatty liver disease (pooled odds ratio (POR) range 1.13-1.56), and risk of CRC. Higher serum high-density lipoprotein cholesterol levels were associated with a lower risk of CRC in 3/6 reviews, while others did not find any association. There was no clear association between high triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol levels, and risk of CRC. CONCLUSION This umbrella review identified that most metabolic factors are significantly associated with increased risk of CRC. Thus, people affected by metabolic factors may be benefited from CRC screening and surveillance.
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Affiliation(s)
- Meseret Derbew Molla
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Biochemistry, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Erin L Symonds
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia; Gastroenterology and Hepatology Department, Flinders Medical Centre, Southern Adelaide Local Health Network, Bedford Park, South Australia, Australia
| | - Jean M Winter
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia
| | - Ayal Debie
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia; Department of Health Systems and Policy, Institute of Public Health, University of Gondar, Gondar, Ethiopia
| | - Molla M Wassie
- Flinders University, College of Medicine and PublicHealth, Flinders Health and Medical Research Institute, Adelaide, South Australia, Australia
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Zhu Z, Lam TYT, Tang RSY, Wong SH, Lui RNS, Ng SSM, Wong SYS, Sung JJY. Triglyceride-glucose index (TyG index) is associated with a higher risk of colorectal adenoma and multiple adenomas in asymptomatic subjects. PLoS One 2024; 19:e0310526. [PMID: 39509387 PMCID: PMC11542827 DOI: 10.1371/journal.pone.0310526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 08/29/2024] [Indexed: 11/15/2024] Open
Abstract
HYPOTHESIS The objective of this study is to evaluate the predictive ability of the TyG index for the presence of adenoma and multiple adenomas in an asymptomatic population. DESIGN A secondary analysis was conducted on a prospective cohort of asymptomatic subjects aged between 50 and 75 who underwent CRC screening. Fasting blood glucose (FBG) and lipid profiles were measured within three months prior colonoscopy. TyG index was estimated as ln [fasting triglycerides (mg/dL) × FBG (mg/dL)/2]. Multivariate logistic regression was performed to assess the association between the TyG index and the risk of adenoma. Its association with multiple adenomas (≥5) and the continuous number of adenomas were assessed by multinomial regression and log-normal linear regression, respectively. RESULTS A total of 1,538 subjects were recruited among which 876 subjects (57%) had at least one adenoma detected. Elevated TyG index was positively associated with the incidence of adenoma (adjusted odds ratio [aOR]: 1.26, 95% confidence interval [CI]: 1.04-1.54). Compared with the lowest TyG index (≤ 8) group, the risk of adenoma was the highest among subjects in the highest TyG index (> 10) group (aOR: 3.36, 95% CI: 1.44-7.73). As compared to the non-adenoma group, the TyG index was also positively associated with multiple adenomas (aOR: 1.74, 95% CI: 1.17-2.57), and the estimate was also the highest in the highest TyG group (aOR: 14.49, 95% CI: 3.12-67.20). As for the number of adenomas, the positive association was maintained (Estimates: 1.06, 95% CI: 1.01-1.12) while the number of adenomas increase the most in the highest TyG index group (Estimates: 1.35, 95% CI: 1.10-1.65). CONCLUSIONS Elevated TyG index is associated with an increased risk of colorectal adenoma and an increased number of adenomas for asymptomatic subjects aged ≥50. TRIAL REGISTRATION This study was registered on clinicaltrials.gov (NCT03597204 and NCT04034953).
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Affiliation(s)
- Ziyue Zhu
- Stanley Ho Big Data Decision Analytics Research Centre, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Thomas Yuen Tung Lam
- The Nethersole School of Nursing, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Raymond Shing Yan Tang
- Institute of Digestive Disease, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Sunny Hei Wong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Rashid Nok Shun Lui
- Institute of Digestive Disease, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Simon Siu Man Ng
- Institute of Digestive Disease, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Samuel Yeung Shan Wong
- The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Joseph Jao Yiu Sung
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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Kumar R, Brown A, Okano S, Simms L, Lord A, O'Sullivan T, Hartel G, Radford-Smith GL. Overweight and obesity are associated with colorectal neoplasia in an Australian outpatient population. Sci Rep 2024; 14:23501. [PMID: 39379529 PMCID: PMC11461741 DOI: 10.1038/s41598-024-74042-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 09/23/2024] [Indexed: 10/10/2024] Open
Abstract
Colorectal cancer is a major cause of cancer-related deaths within the Australian population. Colonoscopy and polypectomy represent effective forms of prevention. Factors such as diabetes, hypertension and dyslipidaemia have been linked to adenoma development across a range of ethnicities, however there are limited data from the Australian population. This study investigates established and potential risk factors for early colorectal neoplasia in an Australian population. This was a prospective, observational case-control study in subjects aged 20-85 years, referred for outpatient colonoscopy. Clinical, anthropometric, and biochemical variables were collected at baseline. Polyps were classified as conventional adenomas or sessile serrated lesions, and correlated with clinical and biochemical variables. The study included 357 subjects, median age 55 years (IQR: 43.0-64.0), and 52.9% were female. 41.7% had metabolic syndrome. Multiple positive associations were observed in those over 40 years and with a BMI ≥ 25, including any polyp (aOR: 2.26; 95%CI: 1.22-4.18); adenoma (aOR: 2.64; 95%CI: 1.31-5.31); and, non-advanced adenoma (aOR: 2.66; 95%CI: 1.25-5.68). Our study demonstrates that elevated BMI is an independent risk factor for colorectal neoplasia in Australians undergoing colonoscopy. Further efforts should be focused on both diet and weight optimization in the general population given these findings and the recent national statistics indicating that almost two-thirds of the population are either overweight or obese.
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Affiliation(s)
- Rina Kumar
- Gut Health Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
- Faculty of Medicine, University of Queensland, Brisbane, QLD, 4072, Australia.
| | - Allison Brown
- Gut Health Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, QLD, 4006, Australia
| | - Satomi Okano
- Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
| | - Lisa Simms
- Gut Health Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
| | - Anton Lord
- Gut Health Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
| | - Timothy O'Sullivan
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, QLD, 4006, Australia
- Gastroenterology and Endoscopy Services, Surgical Treatment and Rehabilitation Service, Brisbane, QLD, 4029, Australia
| | - Gunter Hartel
- Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia
- School of Public Health, University of Queensland, Brisbane, QLD, Australia
- School of Nursing, Queensland University of Technology, Brisbane, QLD, Australia
| | - Graham L Radford-Smith
- Gut Health Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
- Faculty of Medicine, University of Queensland, Brisbane, QLD, 4072, Australia.
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, QLD, 4006, Australia.
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Ungvari Z, Fekete M, Varga P, Lehoczki A, Fekete JT, Ungvari A, Győrffy B. Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk. GeroScience 2024:10.1007/s11357-024-01375-x. [PMID: 39379738 DOI: 10.1007/s11357-024-01375-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 10/01/2024] [Indexed: 10/10/2024] Open
Abstract
The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case-control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24-1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38-1.78, p = 0.01) for males and 1.25 (95% CI = 1.14-1.38, p < 0.01) for females. Case-control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98-1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case-control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case-control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer.
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Affiliation(s)
- Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
| | - Mónika Fekete
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - Peter Varga
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - Andrea Lehoczki
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - János Tibor Fekete
- Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary
| | - Anna Ungvari
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary.
| | - Balázs Győrffy
- Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary
- Dept. of Biophysics, Medical School, University of Pecs, 7624, Pecs, Hungary
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Sundaram S, Lamichhane R, Cecchetti A, Murughiyan U, Sundaram U. Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components. Cancers (Basel) 2024; 16:3350. [PMID: 39409969 PMCID: PMC11482601 DOI: 10.3390/cancers16193350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/20/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM's Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease.
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Affiliation(s)
- Shanmuga Sundaram
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Rajan Lamichhane
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Alfred Cecchetti
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Usha Murughiyan
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Uma Sundaram
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
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Chang YH, Shin CM, Han K, Jung JH, Jin EH, Lim JH, Kang SJ, Choi YJ, Yoon H, Park YS, Kim N, Lee DH. The Persistence of Hypertriglyceridemia and the Risk of Early Onset Colorectal Cancer According to Tumor Subsites: A Nationwide Population-Based Study. Cancer Res Treat 2024; 56:825-837. [PMID: 38147817 PMCID: PMC11261183 DOI: 10.4143/crt.2023.753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 12/19/2023] [Indexed: 12/28/2023] Open
Abstract
PURPOSE The incidence of early-onset colorectal cancer (EoCRC) is increasing worldwide. The association between hypertriglyceridemia (HTG) and EoCRC risk remains unclear. MATERIALS AND METHODS We conducted a nationwide cohort study of 3,340,635 individuals aged 20-49 years who underwent health checkups between 2009 and 2011 under the Korean National Health Insurance Service. HTG was defined as serum triglyceride (TG) level ≥ 150 mg/dL. According to the change in TG status, participants were categorized into persistent normotriglyceridemia (NTG; group 1), NTG to HTG (group 2), HTG to NTG (group 3), and persistent HTG (group 4) groups. The EoCRC incidence was followed up until 2019. RESULTS In total, 7,492 EoCRC cases developed after a mean of 6.05 years of follow-up. Group 4 had the highest risk of EoCRC (adjusted hazard ratio [aHR], 1.097; 95% confidence interval [CI], 1.025 to 1.174). While the risk of rectal cancer was significantly increased in groups 3 and 4 (aHR [95% CI], 1.236 [1.076 to 1.419] and 1.175 [1.042-1.325], respectively), no significant risk differences were observed in right colon cancer. In group 4, male sex and diabetes were associated with a further increased risk of EoCRC (aHR [95% CI], 1.149 [1.082 to 1.221] and 1.409 [1.169 to 1.699], respectively). In addition, there was a dose-response relationship between serum TG levels and the risk of EoCRC (p for trends < 0.0001). CONCLUSION Persistent HTG increased the risk of EoCRC, which was significantly higher only for rectal cancer and marginally higher for other colonic subsites.
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Affiliation(s)
- Young Hoon Chang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Jin Hyung Jung
- Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun Hyo Jin
- Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Joo Hyun Lim
- Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Wu PN, Liu JL, Fang MJ, Fu XS, Wei JL, Wang Y, Qian HH, Zhang D. Global trends in colorectal cancer and metabolic syndrome research: a bibliometric and visualization analysis. Int J Surg 2024; 110:3723-3733. [PMID: 38498393 PMCID: PMC11175816 DOI: 10.1097/js9.0000000000001342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 03/04/2024] [Indexed: 03/20/2024]
Abstract
Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.
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Affiliation(s)
| | | | | | | | | | | | - Hai-Hua Qian
- Department of Anorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Dan Zhang
- Department of Anorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
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Qasim AM, Arif SH. Role of Healthy Lifestyle and Diet Quality in the Development of Colorectal Cancer in the Adult Population in the Kurdistan Region: A Case-Control Study. Cureus 2024; 16:e58764. [PMID: 38779268 PMCID: PMC11111157 DOI: 10.7759/cureus.58764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2024] [Indexed: 05/25/2024] Open
Abstract
Background The incidence of colorectal cancer (CRC) is increasing in developing countries. The factors contributing to the risk of CRC are not known in developing countries. Therefore, this study aimed to explore the role of a healthy lifestyle on CRC in the adult population in the Kurdistan Region of Iraq. Methodology In this case-control investigation, patients previously diagnosed with CRC were included as cases (n = 84) and the healthy adult population as healthy controls (n = 87). The patients were selected from the Gastroenterology Unit of Azadi Teaching Hospital and Emergency Teaching Hospital. The healthy controls were selected from the caregivers of patients who met the eligibility criteria. Results Individuals with a history of chronic disease (63.08% vs. 40.52%; p = 0.0043), a history of hypertension (71.74% vs. 40.80%; p = 0.0003), and a history of inflammatory bowel disease (IBD) (59.42% vs. 42.16%; p = 0.0267) had a significantly higher prevalence of CRC compared to healthy controls. CRC patients had significantly lower diet quality scores than healthy controls (36.27 vs. 37.83; p = 0.0002). The study showed that CRC patients had a significantly lower lifestyle index score compared to healthy controls (10.20 vs. 11.69; p = 0.0002). In addition, CRC patients had lower scores for diet (0.42 vs. 1.00; p < 0.0001), smoking (2.92 vs. 4.0; p < 0.0001), and physical activity (1.02 vs. 1.70; p < 0.0001) compared to healthy controls. However, CRC patients and healthy controls had similar alcohol index scores (5.0 vs. 530; p = 1.000) and body mass index (1.04 vs. 1.01; p = 0.8982). Conclusions This study showed that CRC was associated with having a history of bad diet quality and unhealthy lifestyles. In addition, a history of chronic diseases, hypertension, and IBD was associated with the risk of CRC.
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Affiliation(s)
- Ayid M Qasim
- Infection Control, Duhok General Directorate of Health, Duhok, IRQ
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9
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Li X, Lian Y, Ping W, Wang K, Jiang L, Li S. Abdominal obesity and digestive system cancer: a systematic review and meta-analysis of prospective studies. BMC Public Health 2023; 23:2343. [PMID: 38012596 PMCID: PMC10680266 DOI: 10.1186/s12889-023-17275-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 11/20/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database. METHODS PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests. RESULTS A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method. CONCLUSIONS There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference.
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Affiliation(s)
- Xue Li
- School of Public Health, Shanxi Medical University, Taiyuan, China
| | - Yajun Lian
- Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Weiwei Ping
- Department of Public Health and Preventive Medicine, Changzhi Medical College, 161 Jiefang East Street, Changzhi, 046000, Shanxi, China.
| | - Kunbo Wang
- Xiangya School of Public Health, Central South University, Changsha City, China
| | - Lingyan Jiang
- Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Shaoxia Li
- Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China
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Liu X, Li D, Gao W, Zhao W, Jin L, Chen P, Liu H, Zhao Y, Dong G. Identification of the shared gene signature and biological mechanism between type 2 diabetes and colorectal cancer. Front Genet 2023; 14:1202849. [PMID: 37876593 PMCID: PMC10593476 DOI: 10.3389/fgene.2023.1202849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 09/21/2023] [Indexed: 10/26/2023] Open
Abstract
Background: The correlation of type 2 diabetes mellitus (T2DM) with colorectal cancer (CRC) has garnered considerable attention in the scientific community. Despite this, the molecular mechanisms underlying the interaction between these two diseases are yet to be elucidated. Hence, the present investigation aims to explore the shared gene signatures, immune profiles, and drug sensitivity patterns that exist between CRC and T2DM. Methods: RNA sequences and characteristics of patients with CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. These were investigated using weighted gene co-expression network analysis (WGCNA) to determine the co-expression networks linked to the conditions. Genes shared between CRC and T2DM were analyzed by univariate regression, followed by risk prognosis assessment using the LASSO regression model. Various parameters were assessed through different software such as the ESTIMATE, CIBERSORT, AND SSGSEA utilized for tumor immune infiltration assessment in the high- and low-risk groups. Additionally, pRRophetic was utilized to assess the sensitivity to chemotherapeutic agents in both groups. This was followed by diagnostic modeling using logistic modeling and clinical prediction modeling using the nomogram. Results: WGCNA recognized four and five modules that displayed a high correlation with T2DM and CRC, respectively. In total, 868 genes were shared between CRC and T2DM, with 14 key shared genes being identified in the follow-up analysis. The overall survival (OS) of patients in the low-risk group was better than that of patients in the high-risk group. In contrast, the high-risk group exhibited higher expression levels of immune checkpoints The Cox regression analyses established that the risk-score model possessed independent prognostic value in predicting OS. To facilitate the prediction of OS and cause-specific survival, the nomogram was established utilizing the Cox regression model. Conclusion: The T2DM + CRC risk-score model enabled independent prediction of OS in individuals with CRC. Moreover, these findings revealed novel genes that hold promise as therapeutic targets or biomarkers in clinical settings.
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Affiliation(s)
- Xianqiang Liu
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Dingchang Li
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wenxing Gao
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wen Zhao
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Lujia Jin
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Peng Chen
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Hao Liu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Yingjie Zhao
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Guanglong Dong
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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Jin EH, Choi YJ, Lim JH, Shin CM, Han K, Lee DH. Alteration of Metabolic Syndrome Is Associated with the Decreased Risk of Colorectal Cancer. J Clin Med 2023; 12:4889. [PMID: 37568291 PMCID: PMC10419554 DOI: 10.3390/jcm12154889] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/15/2023] [Accepted: 07/20/2023] [Indexed: 08/13/2023] Open
Abstract
Metabolic syndrome (MetS) can be resolved through active control. We aimed to examine the effect of changes in MetS status on colorectal cancer (CRC) risk. A total of 5,704,611 Korean national insurance beneficiaries that received two consecutive biennial mandatory health exams (2009-2011) were followed-up until 2017. MetS was determined as the presence of at least three of five components. Participants were categorized into four groups according to the change in MetS status; MetS-never, -resolved, -developed, or -persistent. A Cox proportional hazards model adjusted for age, sex, smoking, alcohol drinking, and physical exercise was used. Participants who recovered from MetS had a higher risk of CRC than those free of MetS but had a lower risk than those with persistent MetS (HR: 0.91, 95% CI: 0.86-0.95 vs. HR: 0.75, 95% CI: 0.73-0.78; reference: persistence group). Among the five MetS components, resolving high blood pressure, abdominal obesity, and blood sugar had a preventive effect on CRC prevention, while normalization of lipid profile did not reduce CRC risk independently. Resolving MetS could reduce CRC risk compared to having persistent MetS, indicating the necessity of considering control of MetS as a CRC prevention policy.
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Affiliation(s)
- Eun Hyo Jin
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Republic of Korea; (E.H.J.); (J.H.L.)
| | - Yoon Jin Choi
- Center for Gastric Cancer, National Cancer Center, Goyang-si 10408, Gyeonggi-do, Republic of Korea
| | - Joo Hyun Lim
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 06236, Republic of Korea; (E.H.J.); (J.H.L.)
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Gyeonggi-do, Republic of Korea;
| | - Kyungdo Han
- Department of Biostatistics, College of Medicine, Soongsil University of Korea, Seoul 06978, Republic of Korea;
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Gyeonggi-do, Republic of Korea;
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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12
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Chiang CH, Chang YJ, He SR, Chao JN, Yang CH, Liu YT. Association of 25(OH)-Vitamin D and metabolic factors with colorectal polyps. PLoS One 2023; 18:e0286654. [PMID: 37289677 PMCID: PMC10249833 DOI: 10.1371/journal.pone.0286654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 05/21/2023] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND Studies have revealed the association of vitamin D with specific types of cancer development, however, its correlation with colorectal polyps (CRPs) remains unverified. Our study aimed to investigate the relationship between vitamin D levels, metabolic factors, and CRPs. METHODS A cross-sectional study from 2017 to 2019 involving 1306 participants was conducted to investigate the association among vitamin D levels, metabolic factors, uric acid and CRPs in Taiwan. CRPs diagnoses were determined via colonoscopies conducted by experienced gastrointestinal physicians, and biopsied polyps were inspected under a microscope by experienced pathologists. We employed both simple and multiple logistic regression analyses to identify significant factors associated with CRPs and adenomatous polyps, respectively. RESULTS Our result showed that the prevalence of 25(OH)-vitamin D deficiency (≦ 20 ng/mL) and CRPs was 21.21% and 40.89%, respectively. Multiple logistic regression revealed that the risk of CRPs increased with old age, male sex, hyperglycemia, high triglyceride levels, and low 25(OH)D levels after adjustment for other factors. Besides, low 25(OH)D levels were significantly associated with CRPs risk in women, whereas elevated blood pressure was associated with CRPs risk in men. 25(OH)D Deficiency was revealed to be significantly associated with risk of CRPs in adults over 50 years old. Compared to nonadenomatous polyps, older age, higher 25(OH) vitamin D and higher uric acid levels were at increased risk for adenomatous polyps. CONCLUSIONS Our study revealed that vitamin D deficiency was significantly associated with the risk of CRPs, especially in adults over 50 years old and women. We should therefore be concerned about the CRP risk of vitamin D deficiency and metabolic syndrome (especially hyperglycemia, elevated blood pressure in men, and high triglyceride levels) in this population.
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Affiliation(s)
- Chih-Hsiang Chiang
- Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Jun Chang
- Big Data Center, Changhua Christian Hospital, Changhua, Taiwan
| | - Sin-Ru He
- Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Jih-Ning Chao
- Institute of Statistics, National Chung Hsing University, Taichung City, Taiwan
| | - Chih-Huai Yang
- Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Yen-Tze Liu
- Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan
- Big Data Center, Changhua Christian Hospital, Changhua, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
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13
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Association between the TyG index and TG/HDL-C ratio as insulin resistance markers and the risk of colorectal cancer. BMC Cancer 2022; 22:1007. [PMID: 36138391 PMCID: PMC9503258 DOI: 10.1186/s12885-022-10100-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 09/19/2022] [Indexed: 11/24/2022] Open
Abstract
Background No previous prospective research has explored the association of the TyG (fasting triglyceride-glucose) index and TG/HDL-C ratio as insulin resistance markers with the risk of colorectal cancer (CRC) incidence in the Northern Chinese population. Methods In this prospective cohort study, we included 93,659 cancer-free participants with the measurements of TyG index and TG/HDL-C ratio. Participants were divided by the quartiles of the TyG index or TG/HDL-C ratio. The associations of TyG index, TG/HDL-C ratio, and their components with CRC risk were assessed using Cox proportional hazards regression models. Results During a median follow-up of 13.02 years, 593 incident CRC cases were identified. Compared with the lowest quartile of the TyG index (Q1), the risk of CRC was higher in persons in the third (Q3) and highest quartiles (Q4) of the TyG index, with corresponding multivariable-adjusted HRs (95% CI) of 1.36 (1.06, 1.76) and 1.50 (1.19, 1.91), respectively. The elevated risks of CRC incidence were observed in people in the second, third, and highest quartiles of the TG/HDL-C ratio groups, with corresponding multivariable-adjusted HRs (95% CI) of 1.33 (1.05, 1.70), 1.36 (1.07, 1.73) and 1.37 (1.07, 1.75), respectively. Conclusions Elevated TyG index and TG/HDL-C ratio were associated with a higher risk of developing CRC among adults in Northern China.
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Tao W, Yuan C, Kang B, Liu XY, Cheng YX, Zhang B, Wei ZQ, Peng D. The Effect of Metabolic Syndrome on Colorectal Cancer Prognosis after Primary Surgery. Nutr Cancer 2022; 75:331-338. [PMID: 35976038 DOI: 10.1080/01635581.2022.2112243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE The purpose of this study was to explore whether metabolic syndrome (MetS) affects the prognosis of colorectal cancer (CRC) patients after primary surgery and to analyze the effect of the specific components of MetS on CRC prognosis. METHODS The PubMed, Embase and Cochrane Library databases were searched from inception to July 29, 2021. Overall survival (OS) and disease-free survival (DFS) were compared between the MetS group and the non-MetS group. RESULTS The studies included in the meta-analysis included 4773 patients. All seven studies compared OS between the two groups, and after pooling all hazard ratios (HRs), no significant difference was found between the MetS group and the non-MetS group (HR = 1.17, 95% CI = 0.91 to 1.49, P = 0.21). Four studies compared DFS between the MetS group and the non-MetS group after pooling all the HRs, and there was no difference between the MetS group and the non-MetS group (HR = 1.05, 95% CI = 0.74 to 1.49, P = 0.21). Among the specific components of MetS, high fasting plasma glucose levels (HR = 1.25, 95% CI = 1.00 to 1.58, P = 0.05) had a marginally significant association with poor OS. CONCLUSION MetS may not affect the prognosis of CRC after primary surgery. However, high fasting plasma glucose levels might contribute to poor OS.
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Affiliation(s)
- Wei Tao
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.,Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing, PR China
| | - Chao Yuan
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bing Kang
- Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Yu Liu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Xi Cheng
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bin Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zheng-Qiang Wei
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dong Peng
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Hsu SH, Syu DK, Chen YC, Liu CK, Sun CA, Chen M. The Association between Hypertriglyceridemia and Colorectal Cancer: A Long-Term Community Cohort Study in Taiwan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19137804. [PMID: 35805464 PMCID: PMC9265720 DOI: 10.3390/ijerph19137804] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 02/04/2023]
Abstract
(1) Background: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer deaths worldwide. It often diagnosed at advanced stages, and with increasing incidence at younger generation. CRC poses a heavy financial burden and a huge public health challenge nowadays. Lipoproteins and serum lipids may have an influence on carcinogenesis by making oxidative stress, inflammation, and insulin resistance. Dyslipidemia plays a potential role in the risk of CRC. The purpose of this study is to use nationally representative samples to determine epidemiologic characteristics of CRC in the Taiwanese population, and to evaluate the associations between baseline levels of lipid profile and their effect on risk of colorectal cancer (CRC) comprehensively and quantitatively. The control of dyslipidemia in primary and secondary prevention may reduce the disease burden of CRC. (2) Methods: This is a nationwide long-term community-based prospective cohort study. Data were retrieved from the nationwide population-based Taiwanese Survey on Hypertension, Hyperglycemia and Hyperlipidemia (TwSHHH). Variables were estimated by the Cox proportional hazards model which was then further adjusted for age. We also calculated the relative ratios (RRs) of CRC for joint categories of serum cholesterol, triglyceride (TG), low-density lipoproteins cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level, and to examine their combined effect and statistical interactions. (3) Results: Male, age, waist circumference, diabetes mellitus (DM), high TG, high cholesterol level, smoking history, and metabolic syndrome were proved to increase the risk of CRC. In addition, DM patients with a TG level ≥150 mg/dL and cholesterol ≥180 mg/dL had a 4.118-fold higher risk of CRC as compared with a TG level <150 mg/dL and cholesterol level <180 mg/dL, which was a significant difference (95% CI, 1.061−15.975; p = 0.0407). (4) Conclusions: Patients with DM should control TG and cholesterol level through diet, exercise, or taking medications more aggressively, not only for preventing cardiovascular disease, but also for first prevention of CRC. The study can be valuable for the clinicians and policy makers to implement more precisely goals about dyslipidemia management.
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Affiliation(s)
- Shu-Hua Hsu
- Department of Family Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan Dist., New Taipei City 24352, Taiwan;
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
| | - De-Kai Syu
- Department of Orthopedics, Fu Jen Catholic University Hospital, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan Dist., New Taipei City 24352, Taiwan;
| | - Yong-Chen Chen
- Master Program of Big Data in Biomedicine, College of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
- Data Science Center, College of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan
| | - Chih-Kuang Liu
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
- Department of Urology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan Dist., New Taipei City 24352, Taiwan
| | - Chien-An Sun
- Data Science Center, College of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan
- Department of Public Health, College of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan
- Correspondence: (C.-A.S.); (M.C.)
| | - Mingchih Chen
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
- Artificial Intelligence Development Center, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan
- Correspondence: (C.-A.S.); (M.C.)
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Abstract
OBJECTIVE Investigative studies report contradictory results of the relationship between serum lipid levels and the risk of colorectal cancer (CRC). We conducted a meta-analysis of prospective published studies to clarify the relationship between serum lipid and CRC risk. DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed and Embase from inception until December 2020. ELIGIBILITY CRITERIA We considered prospective cohort and case-control studies that evaluated differences in serum lipid levels with the risk of developing CRC. DATA EXTRACTION AND SYNTHESIS Two independent reviewers screened and included the studies using standardised electronic data extraction forms. The relative risks of the studies were combined with random-effect and fixed-effect models and were analysed for heterogeneity, publication bias and sensitivity. RESULTS Twenty-four prospective studies, including 4 224 317 individuals with 29 499 CRC cases, were included in the meta-analysis. The total pooled risk ratio (RR) for high vs low concentrations of triglyceride (TG) concentrations was reported at 1.21 (95% CI 1.09 to 1.34; I2=46.8%), total cholesterol (TC) was at 1.15 (95% CI 1.08 to 1.22; I2=36.8%), high-density lipoprotein cholesterol (HDL-C) was 0.86 (95% CI 0.77 to 0.97; I2=28.8%) and low-density lipoprotein cholesterol (LDL-C) was observed at 1.03 (95% CI 0.75 to 1.41; I2=69.4%). CONCLUSIONS This meta-analysis shows that high levels of serum TG and TC are positively correlated with the incidence rate of CRC, while high levels of serum HDL-C are negatively correlated with CRC incidence rate. Furthermore, no association was found between LDL-C and the risk of developing CRC. Nevertheless, the heterogeneity brought about by comparative methods, demographic differences and pathological differences between the research subjects limits the effectiveness of the overall pooled results.
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Affiliation(s)
- Zhenpeng Yang
- General Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Huazhen Tang
- General Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Shuai Lu
- General Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
| | - Xibo Sun
- General Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
- Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong, China
| | - Benqiang Rao
- General Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China
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The combination of metabolic syndrome and inflammation increased the risk of colorectal cancer. Inflamm Res 2022; 71:899-909. [PMID: 35715516 PMCID: PMC9307555 DOI: 10.1007/s00011-022-01597-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 05/31/2022] [Indexed: 11/24/2022] Open
Abstract
Background Inflammation and metabolic syndrome (MetS) may act synergistically and possibly accelerate the initiation and progression of colorectal cancer (CRC). We prospectively examined the joint effect of MetS and inflammation on the risk of CRC. Methods We studied 92,770 individuals from the Kailuan study. MetS was defined based on the presence of three or more of the following components. (1) high glucose: FPG > 5.6 mmol/L; (2) high blood pressure: SBP ≥ 130 mmHg or DBP ≥ 85 mmHg; (3) high triglycerides: triglycerides > 1.69 mmol/L; (4) low HDL-C: HDL-C < 1.04 mmol/L in men or 1.29 mmol/L in women; and (5) visceral adiposity: waist circumference ≥ 85 cm in men or 80 cm in women. Inflammation was defined as hs-CRP ≥ 3 mg/L. We divided participants into four groups for the primary exposure according to the presence/absence of inflammation and presence/absence of MetS. Cox proportional hazards regression models were used to evaluate the association of MetS and/or inflammation with the risk of CRC. Results Compared with metabolically healthy noninflammatory individuals, inflammatory participants without MetS and inflammatory participants with MetS were associated with a 1.3-fold and 4.18-fold increased risk of CRC with corresponding HRs (95% CI) of 1.34 (1.09, 1.64) and 4.18 (3.11, 5.62), respectively. The combination of MetS and inflammation was associated with the highest risk of CRC in all subgroups, especially among participants who were female, in younger age, and obese. Sensitivity analyses further validated our primary findings. Conclusions We found the combination of MetS and inflammation could significantly increase the risk of CRC. Including CRP in the diagnosis of MetS may help to identify additional high-risk participants who should be targeted for early diagnosis and prevention of CRC. Trial registration Kailuan study, ChiCTR–TNRC–11001489. Registered 24 August, 2011-Retrospectively registered, http:// www.chictr.org.cn/showprojen.aspx?proj=8050 Supplementary Information The online version contains supplementary material available at 10.1007/s00011-022-01597-9.
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Rothwell JA, Jenab M, Karimi M, Truong T, Mahamat-Saleh Y, Ferrari P, Dashti SG, Kühn T, Cross AJ, Severi G, Gunter MJ, Murphy N. Metabolic Syndrome and Risk of Gastrointestinal Cancers: An Investigation Using Large-scale Molecular Data. Clin Gastroenterol Hepatol 2022; 20:e1338-e1352. [PMID: 34687971 PMCID: PMC9117007 DOI: 10.1016/j.cgh.2021.10.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 09/02/2021] [Accepted: 10/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Gastrointestinal cancer risk is influenced by the presence of metabolic syndrome (MetS). However, previous epidemiologic studies lacked full serological biomarker data for the classification of MetS, and the interaction of MetS with germline cancer risk variants is unknown. METHODS We investigated the associations between MetS and gastrointestinal cancer risk (overall, colorectal, pancreatic, esophageal adenocarcinoma, esophageal squamous cell carcinoma, stomach cardia, stomach non-cardia, hepatocellular carcinoma, and intrahepatic bile duct cancer) in 366,016 United Kingdom Biobank participants with comprehensive serum biomarker and genotype data. MetS status was determined by 3 different definitions at baseline, and, in 15,152 participants, at a repeat assessment after a median of 4.3 years of follow-up. Multivariable hazard ratios and 95% confidence intervals for cancer outcomes were estimated using Cox proportional hazards models. Analyses stratified by polygenic risk score were conducted for colorectal and pancreatic cancers. RESULTS During a median follow-up of 7.1 years, 4238 incident cases of a gastrointestinal cancer occurred. MetS at baseline was associated with higher risk of overall gastrointestinal cancer by any definition (hazard ratio, 1.21; 95% confidence interval, 1.13-1.29, harmonized definition). MetS was associated with increased risks of colorectal cancer, colon cancer, rectal cancer, hepatocellular carcinoma, pancreatic cancer in women, and esophageal adenocarcinoma in men. Associations for colorectal cancer and pancreatic cancer did not differ by polygenic risk score strata (P-heterogeneity 0.70 and 0.69, respectively), and 80% of participants with MetS at baseline retained this status at the repeat assessment. CONCLUSIONS These findings underscore the importance of maintaining good metabolic health in reducing the burden of gastrointestinal cancers, irrespective of genetic predisposition.
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Affiliation(s)
- Joseph A Rothwell
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France.
| | - Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), Lyon, France
| | - Mojgan Karimi
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France
| | - Thérèse Truong
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France
| | - Yahya Mahamat-Saleh
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France
| | - Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), Lyon, France
| | - S Ghazaleh Dashti
- Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Royal Children's Hospital, Victoria, Australia
| | - Tilman Kühn
- Institute for Global Food Security (IGFS), Queen's University Belfast, United Kingdom; Heidelberg Institute of Global Health (HIGH), University of Heidelberg, Heidelberg, Germany
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Gianluca Severi
- Centre for Epidemiology and Population Health (U1018), Exposome and Heredity Team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Gustave Roussy, F-94805, Villejuif, France; Department of Statistics, Computer Science, Applications "G. Parenti," University of Florence, Italy
| | - Marc J Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), Lyon, France
| | - Neil Murphy
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC), Lyon, France
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Kuo YC, Yu LY, Wang HY, Chen MJ, Wu MS, Liu CJ, Lin YC, Shih SC, Hu KC. Effects of Helicobacter pylori infection in gastrointestinal tract malignant diseases: From the oral cavity to rectum. World J Gastrointest Oncol 2022; 14:55-74. [PMID: 35116103 PMCID: PMC8790410 DOI: 10.4251/wjgo.v14.i1.55] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 05/03/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) has infected approximately fifty percent of humans for a long period of time. However, improvements in the public health environment have led to a decreased chance of H. pylori infection. However, a high infection rate is noted in populations with a high incidence rate of gastric cancer (GC). The worldwide fraction of GC attributable to H. pylori is greater than 85%, and a high H. pylori prevalence is noted in gastric mucosa-associated lymphoid tissue lymphoma patients. These results indicate that the majority of GC cases can be prevented if H. pylori infection is eliminated. Because H. pylori exhibits oral-oral or fecal-oral transmission, the relationship between this microorganism and other digestive tract malignant diseases has also attracted attention. This review article provides an overview of H. pylori and the condition of the whole gastrointestinal tract environment to further understand the correlation between the pathogen and the host, thus allowing improved realization of disease presentation.
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Affiliation(s)
- Yang-Che Kuo
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
| | - Lo-Yip Yu
- Department of Internal Medicine, Healthy Evaluation Center, Mackay Memorial Hospital, Taipei 10449, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
| | - Ming-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10051, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10051, Taiwan
| | - Ying-Chun Lin
- Department of Anesthesia, MacKay Memorial Hospital, Taipei 10449, Taiwan
| | - Shou-Chuan Shih
- Division of Gastroenterology, Department of Internal Medicine, Health Evaluate Center, Mackay Memorial Hospital, Taipei 10449, Taiwan
| | - Kuang-Chun Hu
- Department of Internal Medicine, Healthy Evaluation Center, Mackay Memorial Hospital, MacKay Junior College of Medicine, Nursing, and Management, Taipei 10038, Taiwan
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20
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Yu GH, Li SF, Wei R, Jiang Z. Diabetes and Colorectal Cancer Risk: Clinical and Therapeutic Implications. J Diabetes Res 2022; 2022:1747326. [PMID: 35296101 PMCID: PMC8920658 DOI: 10.1155/2022/1747326] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 02/19/2022] [Indexed: 12/24/2022] Open
Abstract
Several epidemiological studies have identified diabetes as a risk factor for colorectal cancer (CRC). The potential pathophysiological mechanisms of this association include hyperinsulinemia, insulin-like growth factor (IGF) axis, hyperglycemia, inflammation induced by adipose tissue dysfunction, gastrointestinal motility disorder, and impaired immunological surveillance. Several studies have shown that underlying diabetes adversely affects the prognosis of patients with CRC. This review explores the novel anticancer agents targeting IGF-1R and receptor for advanced glycation end products (RAGE), both of which play a vital role in diabetes-induced colorectal tumorigenesis. Inhibitors of IGF-1R and RAGE are expected to become promising therapeutic choices, particularly for CRC patients with diabetes. Furthermore, hypoglycemic therapy is associated with the incidence of CRC. Selection of appropriate hypoglycemic agents, which can reduce the risk of CRC in diabetic patients, is an unmet issue. Therefore, this review mainly summarizes the current studies concerning the connections among diabetes, hypoglycemic therapy, and CRC as well as provides a synthesis of the underlying pathophysiological mechanisms. Our synthesis provides a theoretical basis for rational use of hypoglycemic therapies and early diagnosis and treatment of diabetes-related CRC.
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Affiliation(s)
- Guan-Hua Yu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shuo-Feng Li
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ran Wei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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21
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Troelsen FS, Sørensen HT, Pedersen L, Erichsen R. Risk of a post-colonoscopy colorectal cancer in patients with type 2 diabetes: a Danish population-based cohort study. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000786. [PMID: 34952850 PMCID: PMC8710863 DOI: 10.1136/bmjgast-2021-000786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 11/29/2021] [Indexed: 12/30/2022] Open
Abstract
Objective Prevalent type 2 diabetes (T2D) is associated with an increased risk of colorectal cancer and could impair the quality of bowel preparation for colonoscopy. This may in turn increase the risk of overlooked precancerous polyps and subsequent risk of post-colonoscopy colorectal cancer (PCCRC). We investigated whether patients with T2D are at increased risk of PCCRC compared with patients without T2D. Design We conducted a population-based cohort study of patients with T2D and without T2D undergoing colonoscopy in Denmark (1995–2015). We investigated the risk of PCCRC by calculating >6 to 36 months cumulative incidence proportions (CIPs) treating death and colectomy as competing risks. Using Cox proportional-hazards regression analyses, we also computed HRs of PCCRC, comparing patients with T2D and non-T2D. According to the World Endoscopy Organization guidelines, we calculated PCCRC 3-year rates to estimate the proportions of T2D and non-T2D CRC patients experiencing PCCRC. Results We identified 29 031 patients with T2D and 333 232 patients without T2D undergoing colonoscopy. We observed 250 PCCRCs among patients with T2D and 1658 PCCRCs among patients without T2D. The >6 to 36 months CIP after a first-time colonoscopy was 0.64% (95% CI 0.55% to 0.74%) for T2D and 0.36% (95% CI 0.34% to 0.38%) for patients without T2D. The HRs of PCCRC were 1.43 (95% CI 1.21 to 1.72) after a first-time colonoscopy and 1.18 (95% CI 0.75 to 1.85) after a second-time colonoscopy. The PCCRC 3-year rate was 7.9% for patients with T2D and 7.4% for patients without T2D. Conclusion T2D may be associated with an increased HR of PCCRC.
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Affiliation(s)
| | - Henrik Toft Sørensen
- Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark
| | - Lars Pedersen
- Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark
| | - Rune Erichsen
- Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.,Department of Surgery, The Regional Hospital in Randers, Randers, Denmark
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22
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Yu GH, Jiang Z. Progress in understanding of relationship between diabetes and colorectal cancer. Shijie Huaren Xiaohua Zazhi 2021; 29:1323-1333. [DOI: 10.11569/wcjd.v29.i23.1323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Several epidemiological studies have suggested that diabetes is closely associated with an increased risk of colorectal cancer and diabetes could be regarded as an independent risk factor for colorectal cancer. Potential pathophysiological mechanisms connecting diabetes and colorectal cancer include hyperglycemia, hyperinsulinemia, and insulin-like growth factor axis, chronic inflammation and oxidative stress, gastrointestinal motility disorder, and impaired immunological surveillance. Meanwhile, multiple studies have revealed that diabetes is negatively related to the prognosis of patients with colorectal cancer. This review mainly summarizes the current studies concerning the linkages between diabetes and colorectal cancer and the underlying pathophysiological mechanisms, so as to provide a theoretical basis for rational use of antidiabetic drugs and early diagnosis of diabetes-related colorectal cancer.
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Affiliation(s)
- Guan-Hua Yu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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23
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Maki Y, Sueta D, Ishii M, Yamanouchi Y, Fujisue K, Yamanaga K, Nakamura T, Tabata N, Arima Y, Araki S, Yamamoto E, Kaikita K, Chikamoto A, Matsushita K, Matsuoka M, Usuku K, Tsujita K. Associations of cardiovascular risk factors with survival outcomes in a cancer registration: Findings from the KUMAMON registry. Medicine (Baltimore) 2021; 100:e27921. [PMID: 34964764 PMCID: PMC8615348 DOI: 10.1097/md.0000000000027921] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 11/08/2021] [Indexed: 01/05/2023] Open
Abstract
Although the relationship between cardiovascular diseases and malignant diseases has recently attracted attention, the associations of cardiovascular risk factors and clinical outcomes in cancer patients remain to be elucidated. We performed a retrospective, observational study that explored the clinical outcomes of patients with cancer or with a history of cancer.We enrolled 30,706 consecutive adult cancer patients from Kumamoto University Hospital. We investigated mortality and morbidity, including cardiovascular conditions (dyslipidemia [DL]/diabetes mellitus [DM]/hypertension [HT]). The primary endpoint was all-cause mortality.Of the enrolled patients, 9032 patients (29.4%) died within the follow-up period. The Kaplan-Meier analysis demonstrated that in the groups classified according to the number of DL/DM/HT (LDH) factors, the LDH1 and LDH2 groups had a significantly higher probability of the primary endpoint than the LDH0 group (P < .001 and P < .001, respectively), whereas there were no significant differences between the LDH0 group and LDH3 group (P = .963). Univariate Cox proportional hazards regression analyses of mortality complemented by the multiple imputation method including various factors demonstrated that the presence of DL in cancer patients was a significant negative predictor of mortality (hazard ratio = 0.79, P < .01).The all-cause mortality rate did not always increase as the number of LDH factors increased. The present study revealed that the presence of DL is a negative risk factor for all-cause mortality in cancer patients.
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Affiliation(s)
- Yuji Maki
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Daisuke Sueta
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Masanobu Ishii
- Department of Cardiology, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Yoshinori Yamanouchi
- Department of Department of Clinical Investigation, Kumamoto University Hospital, Kumamoto, Japan
| | - Koichiro Fujisue
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
- Medical Quality and Safety Management, Kumamoto University Hospital, Kumamoto, Japan
| | - Kenshi Yamanaga
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Taishi Nakamura
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
- Medical Information Science and Administration Planning, Kumamoto University Hospital, Kumamoto, Japan
| | - Noriaki Tabata
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Yuichiro Arima
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Satoshi Araki
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Eiichiro Yamamoto
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Koichi Kaikita
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
| | - Akira Chikamoto
- Medical Quality and Safety Management, Kumamoto University Hospital, Kumamoto, Japan
- Gastroenterological Surgery, Kumamoto University Hospital, Kumamoto, Japan
| | - Kenichi Matsushita
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
- Division of Advanced Cardiovascular Therapeutics, Kumamoto University Hospital, Kumamoto, Japan
| | - Masao Matsuoka
- Hematology, Rheumatology, and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto Japan
| | - Koichiro Usuku
- Medical Information Science and Administration Planning, Kumamoto University Hospital, Kumamoto, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan
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24
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Tran TT, Gunathilake M, Lee J, Kim J. Association between metabolic syndrome and its components and incident colorectal cancer in a prospective cohort study. Cancer 2021; 128:1230-1241. [PMID: 34762301 DOI: 10.1002/cncr.34027] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 01/20/2023]
Abstract
BACKGROUND Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, reports concerning the association between MetS and colorectal cancer (CRC) have been inconsistent. This study investigated whether MetS, its components, and the number of components increase the risk of CRC. METHODS This was a prospective cohort study of 41,837 participants recruited from August 2002 to December 2014 from the National Cancer Center in South Korea. The participants were followed until December 2017 to identify incident CRC cases. The participants underwent laboratory tests at the baseline. Additionally, a self-administered questionnaire collected information concerning lifestyle and general characteristics at the baseline. A Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to explore the association between MetS and its components and CRC risk after adjustments for confounding variables. RESULTS In total, 128 incident CRC cases were identified during the follow-up period. An increased CRC risk was found among participants with MetS (HR, 1.63; 95% CI, 1.08-2.44). Additionally, elevated blood pressure (HR, 1.50; 95% CI, 1.05-2.15) and a high fasting glucose level (HR, 1.80; 95% CI, 1.23-2.63) were associated with an elevated risk of CRC. Notably, an increased risk was identified among participants with abdominal obesity coexisting with another component of MetS. CONCLUSIONS These results suggest that MetS is a risk factor for CRC. Greater emphasis should be placed on the importance of CRC screening among individuals with abdominal obesity coexisting with another component of MetS. LAY SUMMARY Colorectal cancer (CRC) ranks as the third most common cancer type in terms of incidence. Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, the association between MetS and CRC remains controversial because of a lack of consistent findings in previous studies. In this study, the National Cholesterol Education Program's Adult Treatment Panel III guidelines are used for the diagnosis of MetS. MetS is found to be a predictor of CRC. Additionally, the importance of CRC screening among individuals with 2 components of MetS should be emphasized.
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Affiliation(s)
- Tao Thi Tran
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| | - Madhawa Gunathilake
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
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25
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Jimba T, Kaneko H, Yano Y, Itoh H, Yotsumoto H, Seki H, Morita K, Kiriyama H, Kamon T, Fujiu K, Michihata N, Jo T, Takeda N, Morita H, Nishiyama A, Node K, Yasunaga H, Komuro I. Relation of the Metabolic Syndrome to Incident Colorectal Cancer in Young Adults Aged 20 to 49 Years. Am J Cardiol 2021; 158:132-138. [PMID: 34481589 DOI: 10.1016/j.amjcard.2021.07.049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/08/2021] [Accepted: 07/12/2021] [Indexed: 12/28/2022]
Abstract
Onco-cardiology is the emerging field, and the concept of shared risk factor holds an important position in this field. The increasing prevalence of colorectal cancer (CRC) in young adults is a critical epidemiological issue. Although metabolic syndrome, which is a major risk factor for cardiovascular disease, is known to be associated with CRC incidence in middle-aged and elderly individuals, it is unclear whether this association is present in young adults. We assessed whether metabolic syndrome was associated with CRC events in young adults (aged <50 years), and whether the association differed by the definition of metabolic syndrome. We retrospectively analyzed 902,599 adults (20 to 49 years of age) enrolled in the JMDC Claims Database which is a nationwide epidemiological database in Japan between January 2005 and August 2018. Participants who had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Study participants were categorized into 2 groups according to the presence of metabolic syndrome, defined using the Japanese criteria (waist circumference ≥85 cm for men and ≥90 cm for women, and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). Clinical outcomes were collected between January 2005 and August 2018. The primary outcome was CRC of any stage. Median (interquartile range) age was 41 (37 to 45), and 55.4% were men. Over a median follow-up of 1,008 (429 to 1,833) days, there were 1,884 incidences of CRC. After multivariable adjustment, the hazard ratio (HR) of metabolic syndrome for CRC events was 1.26 (95% confidence interval [CI] = 1.07 to 1.49). Cox regression analysis after multiple imputation for missing values showed that metabolic syndrome was associated with CRC incidence (HR = 1.35, 95% CI = 1.17 to 1.56). Metabolic syndrome was also associated with a higher incidence of CRC in individuals with a follow-up period of ≥365 days (HR = 1.33, 95% CI = 1.10 to 1.60). This association was observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.30, 95% CI = 1.09 to 1.55) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.39, 95% CI = 1.12 to 1.72). In conclusion, metabolic syndrome was associated with a higher incidence of CRC among individuals aged <50 years. These results could be informative for risk stratification of subsequent CRC among young adults.
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Affiliation(s)
- Takahiro Jimba
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidehiro Kaneko
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan; The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan.
| | - Yuichiro Yano
- YCU Center for Novel and Exploratory Clinical Trials, Yokohama City University Hospital, Yokohama, Japan; The Department of Family Medicine and Community Health, Duke University, Durham, North Carolina
| | - Hidetaka Itoh
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Haruki Yotsumoto
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Hikari Seki
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Kojiro Morita
- The Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; The Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Kiriyama
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Kamon
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Katsuhito Fujiu
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan; The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan
| | - Nobuaki Michihata
- The Department of Health Services Research, The University of Tokyo, Tokyo, Japan
| | - Taisuke Jo
- The Department of Health Services Research, The University of Tokyo, Tokyo, Japan
| | - Norifumi Takeda
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Morita
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Akira Nishiyama
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | - Hideo Yasunaga
- The Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Issei Komuro
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
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26
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Tverdal A, Høiseth G, Magnus P, Næss Ø, Selmer R, Knudsen GP, Mørland J. Alcohol Consumption, HDL-Cholesterol and Incidence of Colon and Rectal Cancer: A Prospective Cohort Study Including 250,010 Participants. Alcohol Alcohol 2021; 56:718-725. [PMID: 33604595 PMCID: PMC8557640 DOI: 10.1093/alcalc/agab007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 01/04/2021] [Accepted: 01/16/2021] [Indexed: 11/19/2022] Open
Abstract
Aims Alcohol consumption has been linked to colorectal cancer (CRC) and also to the high-density lipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aim of this study was to investigate the association between self-reported alcohol consumption, HDL-C and incidence of CRC, separately for the two sites. Methods Altogether, 250,010 participants in Norwegian surveys have been followed-up for an average of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up, 3023 and 1439 colon and rectal cancers were registered. Results For men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98–1.12) for colon and 1.08 (1.02–1.15) for rectal cancer. The corresponding figures for women were 1.03 (0.97–1.10) and 1.05 (1.00–1.10). There was a positive association between alcohol consumption and HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62–0.89) per 1 mmol/l) and positively associated with rectal cancer, although not statistically significant (1.15 (0.92–1.44). A robust regression that assigned weights to each observation and exclusion of weights ≤ 0.1 increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. The associations with rectal cancer remained unchanged. Conclusion Our results support a positive association between alcohol consumption and colon and rectal cancer, most pronounced for rectal cancer. Considering the positive relation between alcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in men remains unsettled.
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Affiliation(s)
- Aage Tverdal
- Norwegian Institute of Public Health, Centre for Fertility and Health, Pb 222 Skøyen, 0213 Oslo, Norway
| | - Gudrun Høiseth
- Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, Pb 1171 Blinderen, 0318 Oslo, Norway.,Department of Forensic Sciences, Oslo University Hospital, Pb 4950 Nydalen, 0424 Oslo.,Center for Psychopharmacology, Diakonhjemmet Hospital, Forskningsveien 13, 0373 Oslo, Norway
| | - Per Magnus
- Norwegian Institute of Public Health, Centre for Fertility and Health, Pb 222 Skøyen, 0213 Oslo, Norway
| | - Øyvind Næss
- Institute of Health and Society, University of Oslo, Pb 1171 Blinderen, 0318 Oslo, Norway
| | - Randi Selmer
- Norwegian Institute of Public Health, Division of Chronic Diseases and Aging, Pb 222 Skøyen, 0213 Oslo, Norway
| | - Gun Peggy Knudsen
- Norwegian Institute of Public Health, Division of health data and digitalization, Pb 222 Skøyen, 0213 Oslo, Norway
| | - Jørg Mørland
- Norwegian Centre for Addiction Research (SERAF), Institute of Clinical Medicine, University of Oslo, Pb 1171 Blinderen, 0318 Oslo, Norway.,Norwegian Institute of Public Health, Division of health data and digitalization, Pb 222 Skøyen, 0213 Oslo, Norway
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27
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Shen J, Wu Y, Mo M, Feng X, Zhou C, Wang Z, Cai G, Zheng Y. Risk Factors Associated With Early-Onset Colorectal Neoplasm in Chinese Youth: A Prospective Population-Based Study. Front Oncol 2021; 11:702322. [PMID: 34692479 PMCID: PMC8531514 DOI: 10.3389/fonc.2021.702322] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 09/13/2021] [Indexed: 12/22/2022] Open
Abstract
Evidence of the risk factors associated with early-onset colorectal neoplasm from prospective population-based studies is limited. We enrolled 17,293 participants younger than 50 years from the Shanghai colorectal cancer (CRC) screening program cohort. Face-to-face interviews were performed by trained primary care physicians using a standardized questionnaire to collect the information on potential risk factors at baseline entry. Furthermore, 124 cases of early-onset colorectal neoplasm, including six CRC cases and 118 colorectal adenoma (CRA) cases, were detected between 2012 and 2016. Multivariable logistic regression models and restricted cubic spline (RCS) were used to evaluate the risk factors associated with early-onset colorectal neoplasm. We found that sex, body mass index (BMI), and family history of CRC were associated with the early onset of colorectal neoplasm. The RCS model showed a positive dose–response and linear association between BMI and risk of early-onset colorectal neoplasm among young participants (p-overall = 0.19, p-nonlinear = 0.97). The findings indicated that it was beneficial for normal people younger than 50 years to start opportunistic CRC screening. As for those at high risk, increased surveillance is strongly recommended. Further close follow-up is required for research on the underlying causes of early-onset CRC.
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Affiliation(s)
- Jie Shen
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yiling Wu
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Noninfectious Chronic Disease Control and Prevention, Shanghai Songjiang District Center for Disease Control and Prevention, Shanghai, China
| | - Miao Mo
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaoshuang Feng
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Changming Zhou
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zezhou Wang
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Guoxiang Cai
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ying Zheng
- Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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28
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Metabolic syndrome and the risk of colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis 2021; 36:2215-2225. [PMID: 34331119 DOI: 10.1007/s00384-021-03974-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/08/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS. METHODS PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity. RESULTS MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26-1.47, P < 0.001), men (RR 1.33, 95% CI 1.21-1.47, P < 0.001), and women (RR 1.34, 95% CI 1.19-1.52, P < 0.001). The risk of colorectal cancer seemed to increase as the number of MetS components rose. Moreover, the high body mass index (BMI)/waist circumference (WC) and hyperglycemia were all significantly associated with a higher risk of colorectal cancer (RR 1.28 [1.20-1.37] and 1.31 [1.14-1.50] in both sexes, RR 1.31 [1.19-1.45] and 1.23 [1.03-1.46] in men, and RR 1.22 [1.02-1.46] and 1.63 [1.16-2.28] in women, respectively). CONCLUSIONS MetS was significantly associated with a higher risk of colorectal cancer. The high BMI/WC or hyperglycemia might largely account for this association. Further analysis suggested that, as the number of MetS components increased, the risk of colorectal cancer rose.
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Yang HJ, Cho CW, Jang J, Kim SS, Ahn KS, Park SK, Park DI. Application of deep learning to predict advanced neoplasia using big clinical data in colorectal cancer screening of asymptomatic adults. Korean J Intern Med 2021; 36:845-856. [PMID: 33092313 PMCID: PMC8273821 DOI: 10.3904/kjim.2020.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 03/06/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS We aimed to develop a deep learning model for the prediction of the risk of advanced colorectal neoplasia (ACRN) in asymptomatic adults, based on which colorectal cancer screening could be customized. METHODS We collected data on 26 clinical and laboratory parameters, including age, sex, smoking status, body mass index, complete blood count, blood chemistry, and tumor marker, from 70,336 first-time colonoscopy screening recipients. For reference, we used a logistic regression (LR) model with nine variables manually selected from the 26 variables. A deep neural network (DNN) model was developed using all 26 variables. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of the models were compared in a randomly split validation group. RESULTS In comparison with the LR model (AUC, 0.724; 95% confidence interval [CI], 0.684 to 0.765), the DNN model (AUC, 0.760; 95% CI, 0.724 to 0.795) demonstrated significantly improved performance with respect to the prediction of ACRN (p < 0.001). At a sensitivity of 90%, the specificity significantly increased with the application of the DNN model (41.0%) in comparison with the LR model (26.5%) (p < 0.001), indicating that the colonoscopy workload required to detect the same number of ACRNs could be reduced by 20%. CONCLUSION The application of DNN to big clinical data could significantly improve the prediction of ACRNs in comparison with the LR model, potentially realizing further customization by utilizing large quantities and various types of biomedical information.
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Affiliation(s)
- Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang Woo Cho
- Department of Bioinformatics, Soongsil University, Seoul, Korea
| | - Jongha Jang
- Department of Bioinformatics, Soongsil University, Seoul, Korea
| | - Sang Soo Kim
- Department of Bioinformatics, Soongsil University, Seoul, Korea
| | - Kwang-Sung Ahn
- Functional Genome Institute, PDXen Biosystems Inc., Seoul, Korea
| | - Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Correspondence to Dong Il Park, M.D. Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea Tel: +82-2-2001-8555 Fax: +82-2-2001-8360 E-mail:
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Okamura T, Hashimoto Y, Hamaguchi M, Obora A, Kojima T, Fukui M. Visceral Adiposity Index is a predictor of incident colorectal cancer: a population-based longitudinal study. BMJ Open Gastroenterol 2021; 7:bmjgast-2020-000400. [PMID: 32595114 PMCID: PMC7322272 DOI: 10.1136/bmjgast-2020-000400] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/26/2020] [Accepted: 05/11/2020] [Indexed: 12/14/2022] Open
Abstract
Objective The Visceral Adiposity Index (VAI) is a marker of visceral fat accumulation and dysfunction. We aimed to investigate the association between VAI and incident colorectal cancer (CRC). Design In this historical cohort study of 27 921 (16 434 men and 11 487 women) participants, we divided the participants into tertiles according to VAI. We calculated VAI: men, VAI = (waist circumference (WC)/(39.68+1.88 × body mass index (BMI))) × (triglycerides (TG)/1.03) × (1.31/high-density lipoprotein cholesterol (HDL)); women, VAI = (WC/(36.58+1.89 × BMI)) × (TG/0.81) × (1.52/HDL). We performed Cox proportional hazard models, adjusting for sex, age, smoking, alcohol consumption, exercise, haemoglobin A1c and systolic blood pressure. Results During the median 4.4-year follow-up, 116 participants developed CRC. Compared with the lowest tertile, the HRs of incident CRC in the middle and the highest tertiles were 1.30 (95% CI 0.76 to 2.28, p=0.338) and 2.41 (1.50 to 4.02, p<0.001) in univariate analysis. Moreover, the HRs of incident CRC in the middle and the highest tertiles were 1.27 (0.73 to 2.23, p=0.396) and 1.98 (1.15 to 3.39, p=0.013) after adjusting for covariates. Conclusions VAI can be a predictor of incident CRC. For early detection, we should encourage people with high VAI to undergo screening for CRC.
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Affiliation(s)
- Takuro Okamura
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Akihiro Obora
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Takao Kojima
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
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Ku MS, Chiu SYH, Chien KL, Lee YC, Chen SLS, Chen CD. Gender difference in metabolic syndrome and incident colorectal adenoma: A prospective observational study (KCIS No.42). Medicine (Baltimore) 2021; 100:e26121. [PMID: 34087861 PMCID: PMC8183717 DOI: 10.1097/md.0000000000026121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 04/18/2021] [Accepted: 05/10/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT This community-based study aimed to elucidate whether there is a gender difference in the effect of metabolic syndrome (MetS) and its individual components on an elevated risk for incident colorectal adenoma.A prospective cohort study was conducted by enrolling 59,767 subjects aged 40 years or older between 2001 and 2009 in Keelung, Taiwan, to test this hypothesis, excluding those with a prior history of colorectal cancer and those with colorectal cancer diagnosed at the first screening. Cox proportional hazards regression models were used to assess the effect of MetS in terms of a dichotomous classification, each individual component and the number of components for males and females.Colorectal adenoma was present in 2.7% (n = 652) of male participants and 1.1% (n = 403) of female participants. The prevalence rate of MetS was 26.7% and 23.3% for males and females, respectively. The effect of MetS on colorectal adenoma was statistically significant and similar for the 2 genders, with an adjusted hazard ratio (aHR) of 1.33 (95% CI: 1.13-1.58) in males and 1.33 (95% CI: 1.06-1.66) in females after adjustment for confounders. However, MetS led to higher risk of advanced colorectal adenoma in men than in women. Regarding the effect of each component of MetS on colorectal adenoma, abnormal waist circumference and hypertriglyceridemia led to an elevated risk of colorectal adenoma in both genders. A rising risk of colorectal adenoma among females was noted in those with a moderately higher level of glycemia (100-125 mg/dL, aHR = 1.44, 95% CI: 1.12-1.85). Hypertriglyceridemia and high blood pressure were associated with an increased risk of advance colorectal adenoma in males.Both male and female subjects with MetS had a higher risk of colorectal adenoma. The contributions from individual components of MetS varied by gender. These findings suggest that the possible risk reduction of colorectal adenoma through metabolic syndrome-based lifestyle modifications may differ between genders.
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Affiliation(s)
- Mei-Sheng Ku
- Institute of Environmental and Occupational Health Science, College of Public Health, National Taiwan University, Taipei
| | - Sherry Yueh-Hsia Chiu
- Department of Health Care Management, College of Management, Chang Gung University, Taoyuan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public School
- Department of Internal Medicine, College of Medicine
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University
| | - Yi-Chia Lee
- Institute of Epidemiology and Preventive Medicine, College of Public School
- Department of Internal Medicine, College of Medicine
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University
- Department of Medical Research, National Taiwan University Hospital
| | - Sam Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei
| | - Chih-Dao Chen
- Department of Family Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
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Mahboobnia K, Pirro M, Marini E, Grignani F, Bezsonov EE, Jamialahmadi T, Sahebkar A. PCSK9 and cancer: Rethinking the link. Biomed Pharmacother 2021; 140:111758. [PMID: 34058443 DOI: 10.1016/j.biopha.2021.111758] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/17/2021] [Accepted: 05/20/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Cancer is emerging as a major problem globally, as it accounts for the second cause of death despite medical advances. According to epidemiological and basic studies, cholesterol is involved in cancer progression and there are abnormalities in cholesterol metabolism of cancer cells including prostate, breast, and colorectal carcinomas. However, the importance of cholesterol in carcinogenesis and thereby the role of cholesterol homeostasis as a therapeutic target is still a debated area in cancer therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9), a serine protease, modulates cholesterol metabolism by attachment to the LDL receptor (LDLR) and reducing its recycling by targeting the receptor for lysosomal destruction. Published research has shown that PCSK9 is also involved in degradation of other LDLR family members namely very-low-density-lipoprotein receptor (VLDLR), lipoprotein receptor-related protein 1 (LRP-1), and apolipoprotein E receptor 2 (ApoER2). As a result, this protein represents an interesting therapeutic target for the treatment of hypercholesterolemia. Interestingly, clinical trials on PCSK9-specific monoclonal antibodies have reported promising results with high efficacy in lowering LDL-C and in turn reducing cardiovascular complications. It is important to note that PCSK9 mediates several other pathways apart from its role in lipid homeostasis, including antiviral activity, hepatic regeneration, neuronal apoptosis, and modulation of various signaling pathways. Furthermore, recent literature has illustrated that PCSK9 is closely associated with incidence and progression of several cancers. In a number of studies, PCSK9 siRNA was shown to effectively suppress the proliferation and invasion of the several studied tumor cells. Hence, a novel application of PCSK9 inhibitors/silencers in cancer/metastasis could be considered. However, due to poor data on effectiveness and safety of PCSK9 inhibitors in cancer, the impact of PCSK9 inhibition in these pathological conditions is still unknown. SEARCH METHODS A vast literature search was conducted to find intended studies from 1956 up to 2020, and inclusion criteria were original peer-reviewed publications. PURPOSE OF REVIEW To date, PCSK9 has been scantly investigated in cancer. The question that needs to be discussed is "How does PCSK9 act in cancer pathophysiology and what are the risks or benefits associated to its inhibition?". We reviewed the available publications highlighting the contribution of this proprotein convertase in pathways related to cancer, with focus on the potential implications of its long-term pharmacological inhibition in cancer therapy.
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Affiliation(s)
- Khadijeh Mahboobnia
- Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Matteo Pirro
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
| | - Ettore Marini
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
| | - Francesco Grignani
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
| | - Evgeny E Bezsonov
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Institute of Human Morphology, 3 Tsyurupa Street, Moscow 117418, Russia; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, Russia
| | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Wang CL, Hsu PS, Lin CY, Yang SF. Clinical Factors Associated with Asymptomatic Women Having Inconclusive Screening Mammography Results: Experiences from a Single Medical Center in Taiwan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18105410. [PMID: 34069375 PMCID: PMC8158679 DOI: 10.3390/ijerph18105410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/11/2021] [Accepted: 05/17/2021] [Indexed: 11/16/2022]
Abstract
Screening mammography is used worldwide for the early detection of breast cancer in women experiencing no symptoms. The Breast Imaging Reporting and Database System (BI-RADS) is used to report mammographic findings. However, little is known about the clinical characteristics of Asian women with BI-RADS category 0, and we aimed to explore such characteristics in the context of Taiwan. This retrospective cross-sectional study was conducted using data from a single tertiary medical center. We examined the association of blood test data and estrogen exposure–related medical histories with BI-RADS reports from screening mammography of 4280 women between 1 January 2010 and 31 July 2019. The data of 4280 participants were evaluated, and they were categorized into BI-RADS category 0 (n = 413; 9.6%) and 1–5 (n = 3867; 90.4%) subgroups. In a multivariate analysis, breast surgery history and premenopausal status had a positive relationship with a category 0 status, with respective risk increases of 64% and 34% (p = 0.010 and 0.013). Hormone contraceptive use for ≥5 years was a negative independent predictor of having a category 0 status. In conclusion, breast surgery history and premenopausal status significantly increased the likelihood of individuals having incomplete mammographic findings, even when they were older than 45 years. Identifying related factors before screening mammography is helpful for clinical physicians to arrange more proper and alternative examination and obtain a definite diagnosis.
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Affiliation(s)
- Chun-Li Wang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Family Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan;
| | - Pi-Shan Hsu
- Department of Family Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan;
- Graduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung-Hsing University, Taichung 40227, Taiwan
| | - Chia-Yen Lin
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- Correspondence: (C.-Y.L.); (S.-F.Y.)
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40705, Taiwan
- Correspondence: (C.-Y.L.); (S.-F.Y.)
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Abstract
The incidence and mortality associated with colorectal cancer (CRC) diagnosed in patients under the age of 50 have been steadily increasing. The exact etiology of these epidemiologic trends is unclear. This chapter will provide a comprehensive review on the topic of early age onset colorectal cancer (EAO-CRC), defined as colorectal cancer (CRC) diagnosed in patients under the age of 50. Topics reviewed will include the epidemiology of EAO-CRC around the world, clinical and pathological features of EAO-CRC in contrast to later age onset CRC (CRC diagnosed on those over the age of 50) and the observed molecular and somatic characteristics. This chapter will review the etiologies to EAO-CRC and the established, as well as proposed risk factors for disease. Evidence-based approaches to prevention, early detection, treatment and survivorship will be presented.
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Affiliation(s)
- Swati G Patel
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, United States.
| | - Caitlin C Murphy
- Division of Epidemiology, Department of Population & Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Christopher H Lieu
- Division of Medical Oncology, Gastrointestinal Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Heather Hampel
- Division of Human Genetics, Biospecimen Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States
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Kim NH, Jung YS, Park JH, Park DI, Sohn CI. Impact of nonalcoholic fatty liver disease on the risk of metachronous colorectal neoplasia after polypectomy. Korean J Intern Med 2021; 36:557-567. [PMID: 32630984 PMCID: PMC8137416 DOI: 10.3904/kjim.2019.360] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 01/09/2020] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND/AIMS Metabolic syndrome has been reported to be a risk factor for metachronous colorectal neoplasia (CRN). However, the impact of nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, on the development of metachronous CRN after polypectomy has been rarely examined. We evaluated the association between NAFLD and the development of metachronous CRN after polypectomy. METHODS Asymptomatic subjects who underwent abdominal ultrasonography and endoscopic removal of ≥ 1 adenomas at the index colonoscopy between 2010 and 2014, and had a follow-up surveillance colonoscopy until 2017 were analyzed. RESULTS Of 6,182 participants, 2,642 (42.7%) had NAFLD at the time of the index colonoscopy. Patients with NAFLD had significantly higher cumulative incidence rates of metachronous overall CRN than those without NAFLD in both men (19.4% vs. 18.2% at 3 years and 49.2% vs. 44.0% at 5 years; p = 0.001) and women (18.7% vs. 10.5% at 3 years and 56.1% vs. 29.8% at 5 years; p < 0.001). Even after adjusting for confounders, NAFLD remained independently associated with an increased risk of metachronous overall CRN in both men (adjusted hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.06 to 1.29) and women (adjusted HR, 1.63; 95% CI, 1.27 to 2.07). Additionally, NAFLD was an independent risk factor for metachronous advanced CRN (ACRN) in women (adjusted HR, 2.61; 95% CI, 1.27 to 5.37). CONCLUSION NAFLD is related to an increased risk of metachronous CRN after polypectomy. Especially, women with NAFLD are at an increased risk of developing metachronous ACRN. Our results indicate a possible effect of NAFLD on the pathogenesis of CRN.
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Affiliation(s)
- Nam Hee Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Correspondence to Yoon Suk Jung, Ph.D. Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea Tel: +82-2-2001-8577 Fax: +82-2-2001-2049 E-mail:
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Silva A, Pereira SS, Monteiro MP, Araújo A, Faria G. Effect of Metabolic Syndrome and Individual Components on Colon Cancer Characteristics and Prognosis. Front Oncol 2021; 11:631257. [PMID: 33747952 PMCID: PMC7970759 DOI: 10.3389/fonc.2021.631257] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/22/2021] [Indexed: 12/25/2022] Open
Abstract
Metabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, whether the cluster of metabolic changes that define MS also influence CC prognosis remains unclear. Thus, our aim was to investigate whether the presence of MS or any of the MS individual components could provide prognostic information on tumor phenotype and survival outcomes. Clinical and pathological data from patients with CC (n = 300) who underwent surgical resection at a single tertiary hospital were retrospectively collected to evaluate presence of MS components and diagnostic criteria, CC phenotype and disease outcomes. Patients were allocated into two groups according to the presence or absence of MS (n = 85 MS vs n = 83 non-MS). The overall prevalence of MS individual components was 82.7% for increased waist-circumference (WC), 61.3% for high blood pressure (BP), 48.8% for low HDL-cholesterol, 39.9% for high fasting glucose, and 33.9% for hypertriglyceridemia. Patients in the MS group presented smaller tumors (p = 0.006) with lower T-stage (p = 0.002). High BP (p = 0.029) and hypertriglyceridemia (p = 0.044) were associated with a smaller tumor size, while low-HDL (p = 0.008) was associated with lower T-stage. After propensity score matching using age, tumor size and staging as covariates high-BP (p = 0.020) and WC (p = 0.003) were found to influence disease-free survival, but not overall survival. In conclusion, despite MS being an established risk factor for CC, our data does not support the hypothesis that MS components have a negative impact on disease extension or prognosis. Nevertheless, a protective role of BP and lipid lowering drugs cannot be excluded.
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Affiliation(s)
- Ana Silva
- Pharmacy Department, Centro Hospitalar Universitário do Porto, Porto, Portugal.,School of Health, Polytechnic Institute of Porto, Polytechnic of Porto, Porto, Portugal
| | - Sofia S Pereira
- Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Biomedical Research (UMIB) of Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Mariana P Monteiro
- Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Biomedical Research (UMIB) of Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.,Centre for Obesity Research, University College London, London, United Kingdom
| | - António Araújo
- Unit of Oncobiology Research, Unit for Multidisciplinary Biomedical Research (UMIB) of Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.,Medical Oncology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Gil Faria
- iGo Department, CINTESIS-Center for Research in Health Technologies and Information Systems, Porto, Portugal.,General Surgery, Hospital de Pedro Hispano - Unidade Local de Saúde de Matosinhos, Senhora da Hora, Portugal.,Department of Surgery, Faculty of Medicine, University of Porto, Porto, Portugal
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Du L, Cheng Q, Zheng H, Liu J, Liu L, Chen Q. Targeting stemness of cancer stem cells to fight colorectal cancers. Semin Cancer Biol 2021; 82:150-161. [PMID: 33631296 DOI: 10.1016/j.semcancer.2021.02.012] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 01/12/2021] [Accepted: 02/19/2021] [Indexed: 02/07/2023]
Abstract
Cancer initiating/ stem cells (CSCs) undergo self-renewal and differentiation that contributes to tumor initiation, recurrence and metastasis in colorectal cancer (CRC). Targeting of colorectal cancer stem cells (CCSCs) holds significant promise in eradicating cancer cells and ultimately curing patients with cancer. In this review, we will introduce the current progress of CCSC studies, including the specific surface markers of CCSCs, the intrinsic signaling pathways that regulate the stemness and differentiation characteristics of CCSCs, and the tumor organoid model for CCSC research. We will focus on how these studies will lead to the progress in targeting specific surface markers or signaling pathways on CCSCs by monoclonal antibodies, or by natural or synthetic compounds, or by immunotherapy. As CSCs are highly heterogeneous and plastic, we suggest that combinatory approaches that target the stemness network may represent an important strategy for eradicating cancers.
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Affiliation(s)
- Lei Du
- The State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine. Beijing, 100101, China.
| | - Qi Cheng
- The State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; The Graduate University of Chinese Academy of Sciences. Beijing, 100049, China
| | - Hao Zheng
- The State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Jinming Liu
- The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Lei Liu
- The State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine. Beijing, 100101, China
| | - Quan Chen
- The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
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Xuan K, Zhao T, Sun C, Patel AS, Liu H, Chen X, Qu G, Sun Y. The association between hypertension and colorectal cancer: a meta-analysis of observational studies. Eur J Cancer Prev 2021; 30:84-96. [PMID: 32039929 DOI: 10.1097/cej.0000000000000578] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The relationship between hypertension and risk of colorectal cancer (CRC) is unclear. This meta-analysis aims to explore the association between them. Six databases were searched for studies published before August 2019. The pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated to estimate the association between the hypertension and CRC risk. A total of 2841 potentially relevant articles were obtained, and 25 studies with a pooled 1.95 million participants were finally included in the meta-analysis. These results suggested a positive association between hypertension and risk of CRC with a pooled RR of 1.15 (95% CI: 1.08, 1.23). Male patients with hypertension had a 13% (95% CI: 1.06, 1.20) increased risk of CRC. The risk of colon cancer and rectal cancer in male patients was 1.17 (95% CI: 1.01, 1.36) and 1.35 (95% CI: 1.04, 1.74), respectively, while no association between hypertension and the risk of CRC in females was elucidated. This meta-analysis demonstrated that a positive association between hypertension and CRC exists, with male patients having a higher risk of developing CRC than female patients.
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Affiliation(s)
- Kun Xuan
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Tianming Zhao
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Chenyu Sun
- AMITA Health Saint Joseph Hospital Chicago
| | - Akash S Patel
- University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA
| | - Haixia Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Xin Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Guangbo Qu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yehuan Sun
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Center for Evidence-Based Practice, Anhui Medical University, Hefei, Anhui, China
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Han F, Wu G, Zhang S, Zhang J, Zhao Y, Xu J. The association of Metabolic Syndrome and its Components with the Incidence and Survival of Colorectal Cancer: A Systematic Review and Meta-analysis. Int J Biol Sci 2021; 17:487-497. [PMID: 33613107 PMCID: PMC7893592 DOI: 10.7150/ijbs.52452] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 11/13/2020] [Indexed: 12/22/2022] Open
Abstract
Background: This meta-analysis was aimed to quantitatively assess the associations of metabolic syndrome (MetS) and its components with colorectal cancer (CRC). Methods: PubMed, EMBASE and Web of Science databases were systematically searched for eligible studies. A total of 18 studies for CRC incidence and 12 studies for CRC mortality were identified. Results: MetS was associated with an increased risk of CRC incidence and mortality in male (RR: 1.28, 95 % CI 1.16-1.39, and 1.24, 1.18-1.31, respectively) and correlated with an increased risk of CRC incidence in female (RR: 1.21, 1.13-1.30), but not with CRC mortality in female. MetS increased the risk of cancer-specific mortality (RR: 1.72, 1.03-2.42), but not overall mortality. The risk estimates of CRC incidence changed little depending on age, sex, cancer site, the type of studies, ethnicity, publication year, or definition of MetS. As for CRC mortality, further stratified analyses indicated statistical significance in studies with assessing cancer-specific survival outcome, in male, a cohort design, ethnicity of non-Chinese or with definition of MetS as ≥ 3 metabolic abnormalities. Obesity and hyperglycemia are risk factors of CRC incidence in both male and female. Only dysglycemia is the risk factor for CRC mortality. Conclusions: MetS is associated with an increased risk of CRC incidence and cancer-specific mortality, but not overall mortality. In addition, MetS may increase the CRC mortality in male rather than in female. However, since most of the studies on CRC mortality were conducted in Chinese, further studies are needed to clarify this connection.
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Affiliation(s)
- Fei Han
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
| | - Guanghai Wu
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Shuai Zhang
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Judong Zhang
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Yongjie Zhao
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Jing Xu
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
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Engin O, Kilinc G, Salimoglu S. Trends, Risk Factors, and Preventions in Colorectal Cancer. COLON POLYPS AND COLORECTAL CANCER 2021:213-233. [DOI: 10.1007/978-3-030-57273-0_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Kim J, Park EY, Park E, Lim MK, Oh JK, Kim B. Metabolic Syndrome and Colorectal Cancer Risk: Results of Propensity Score-Based Analyses in a Community-Based Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17228687. [PMID: 33238496 PMCID: PMC7700241 DOI: 10.3390/ijerph17228687] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 11/18/2020] [Accepted: 11/20/2020] [Indexed: 12/24/2022]
Abstract
Background: This study aimed to determine the effects of metabolic syndrome (MetS) on colorectal cancer (CRC) using propensity score (PS) methods. Methods: The study subjects were 2417 men and 4568 women from the Korean National Cancer Center (KNCC) Community Cohort enrolled between 2003 and 2010. Odds risks (ORs) and 95% confidence intervals (CIs) using PS matching analysis, regression models adjusted by the PS or stratified into five strata according to PS, and PS weighting methods were calculated. Results: In women, MetS and abnormally high triglyceride (TG) levels were associated with CRC risk using the PS matching analysis (ORs, for MetS, 2.19 (95% CI, 1.10–4.33); for abnormal TG levels, 2.08 (95% CI, 1.07–4.02)). However, there were no significant associations between MetS and TG levels and CRC risk in men. Conclusions: Our study might provide additional evidence that deteriorated metabolic profiles increase the risk of CRC in women rather than men. Thus, this may have an important role in effective population-level interventions for deteriorated metabolic profiles at an early stage.
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Affiliation(s)
- Jinsun Kim
- Division of Cancer Prevention & Early Detection, National Cancer Control Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Korea; (J.K.); (E.P.); (J.-K.O.); (B.K.)
| | - Eun Young Park
- Division of Cancer Prevention & Early Detection, National Cancer Control Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Korea; (J.K.); (E.P.); (J.-K.O.); (B.K.)
- Correspondence:
| | - Eunjung Park
- Division of Cancer Prevention & Early Detection, National Cancer Control Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Korea; (J.K.); (E.P.); (J.-K.O.); (B.K.)
| | - Min Kyung Lim
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do 10408, Korea;
| | - Jin-Kyoung Oh
- Division of Cancer Prevention & Early Detection, National Cancer Control Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Korea; (J.K.); (E.P.); (J.-K.O.); (B.K.)
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do 10408, Korea;
| | - Byungmi Kim
- Division of Cancer Prevention & Early Detection, National Cancer Control Institute, National Cancer Center, Goyang-si, Gyeonggi-do 10408, Korea; (J.K.); (E.P.); (J.-K.O.); (B.K.)
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Chang JW, Shin DW, Han KD, Jeon KH, Yoo JE, Cho IY, Choi YJ, Hong JY. Obesity Has a Stronger Relationship with Colorectal Cancer in Postmenopausal Women than Premenopausal Women. Cancer Epidemiol Biomarkers Prev 2020; 29:2277-2288. [PMID: 32868317 DOI: 10.1158/1055-9965.epi-20-0594] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/16/2020] [Accepted: 08/26/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND To examine the relationship between obesity measured by waist circumference (WC) and body mass index (BMI) and the incidence of colorectal cancer in premenopausal and postmenopausal women. METHODS A total of 1,418,180 premenopausal and 4,854,187 postmenopausal women without cancer at baseline and ages over 40 were identified using the Korean National Health Insurance System Cohort during 2009 to 2014. The hazard ratio (HR) for colorectal cancer incidence was assessed according to menopausal state using Cox proportional hazards models. RESULTS During a mean follow-up period of 7.2 years, 7,094 and 57,449 colorectal cancer cases occurred in premenopausal and postmenopausal women, respectively. Compared with the reference group (WC 65-75), the HRs [95% confidence interval (CI)] of colorectal cancer in WC <65, 75-85, 85-95, and >95 groups were 1.01 (0.91-1.11), 1.02 (0.97-1.07), 1.09 (1.00-1.18), and 1.31 (1.12-1.52), respectively, in premenopausal women and 1.01 (0.95-1.17), 1.09 (1.07-1.12), 1.19 (1.00-1.18), and 1.30 (1.25-1.35), respectively, in postmenopausal women. Compared with the reference group (BMI 18.5-22.9), HRs (95% CI) for colorectal cancer in BMI <18.5, 23-25, 25-30, and >30 groups were 0.99 (0.87-1.14), 0.99 (0.94-1.06), 0.98 (0.92-1.04), and 1.06 (0.92-1.20), respectively, in premenopausal women. In postmenopausal women, those values were 0.99 (0.93-1.05), 1.05 (1.03-1.08), 1.11 (1.09-1.13), and 1.20 (1.16-1.25), respectively. CONCLUSIONS WC is associated with the risk of colorectal cancer in both groups of women, but this association was stronger in postmenopausal women than in premenopausal women. BMI increased the incidence of colorectal cancer only in postmenopausal women IMPACT: Obesity has a stronger relationship with colorectal cancer in postmenopausal women than in premenopausal women.
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Affiliation(s)
- Ji Won Chang
- Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Wook Shin
- Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. .,Center for Clinical Epidemiology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea
| | - Kyung Do Han
- Department of Statistics and Actuarial Science, Soongsil University Soongsil University, Seoul, Korea
| | - Keun Hye Jeon
- Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Eun Yoo
- Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.,Department of Economics and Center for Economic and Social Research, University of Southern California, Los Angeles, and RAND Corporation, Santa Monica, California
| | - In Young Cho
- Department of Family Medicine, Kangbuk Samsung Hospital, Seoul, Korea
| | - Yun Jin Choi
- Department of Internal Medicine, Severance Hospital, Seoul, Korea
| | - Jung Yong Hong
- Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Chiang CL, Huang HH, Huang TY, Shih YL, Hsieh TY, Lin HH. Nonalcoholic Fatty Liver Disease Associated With Bladder Cancer. Am J Med Sci 2020; 360:161-165. [DOI: 10.1016/j.amjms.2020.04.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 02/29/2020] [Accepted: 04/24/2020] [Indexed: 12/17/2022]
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Okamura T, Hashimoto Y, Hamaguchi M, Obora A, Kojima T, Fukui M. Triglyceride-glucose index (TyG index) is a predictor of incident colorectal cancer: a population-based longitudinal study. BMC Endocr Disord 2020; 20:113. [PMID: 32709256 PMCID: PMC7379831 DOI: 10.1186/s12902-020-00581-w] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 06/22/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC), which is related with insulin resistance, is a one of the most common cancers. Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We conducted the investigation of association between TyG index and incident CRC. METHODS We examined the affect of TyG index on incident CRC in this historical cohort study of 27,944 (16,454 men and 11,490 women) participants. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The impact of TyG index on incident CRC was investigated using Cox proportional hazard models, adjusting for sex, age, body mass index, smoking status, alcohol consumption, exercise, systolic blood pressure and creatinine. The covariate-adjusted receiver operating characteristic (ROC) curve calculated the area under the curve (AUC) and cut-off value of TyG index for the incidence of CRC. RESULTS During the median 4.4-year follow-up, 116 participants were diagnosed as CRC. The cumulative incidence rate of CRC were 0.4%. In Cox proportional hazard model, the HRs of TyG index were 1.38 (95% Confidence interval (CI), 1.00-1.91, p = 0.049) after adjusting for covariates. In the covariate-adjusted ROC curve analysis, the cut-off value of TyG index for incident CRC was 8.272 (AUC 0.687 (95%CI, 0.637-737, sensitivity = 0.620, specificity = 0.668, p < 0.001)). CONCLUSIONS TyG index can predict the onset of CRC. For early detection of CRC, we should encourage people with high TyG index to undergo screening for CRC.
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Affiliation(s)
- Takuro Okamura
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Akihiro Obora
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Takao Kojima
- Department of Gastroenterology, Asahi University Hospital, Gifu, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Lee J, Lee KS, Kim H, Jeong H, Choi MJ, Yoo HW, Han TH, Lee H. The relationship between metabolic syndrome and the incidence of colorectal cancer. Environ Health Prev Med 2020; 25:6. [PMID: 32075578 PMCID: PMC7031951 DOI: 10.1186/s12199-020-00845-w] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 02/12/2020] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES This study evaluated the incidence of colorectal cancer (CRC) according to the number of metabolic syndrome (MetS) components. METHODS Using health checkup and insurance claims data of 6,365,409 subjects, the occurrence of CRC according to stage of MetS by sex was determined from the date of the health checkup in 2009 until December 31, 2018. RESULTS Cumulative incidence rates (CIR) of CRC in men and women was 3.9 and 2.8 per 1000 (p < 0.001), respectively. CIR of CRC for the normal, pre-MetS, and MetS groups in men was 2.6, 3.9, and 5.5 per 1000 (p < 0.001) and CIR in women was 2.1, 2.9, and 4.5 per 1000 (p < 0.001), respectively. Compared with the normal group, the hazard ratio (HR) of CRC for the pre-MetS group was 1.25 (95% CI 1.17-1.33) in men and 1.09 (95% CI 1.02-1.17) in women, and the HR of CRC for the MetS group was 1.54 (95% CI 1.43-1.65) in men and 1.39 (95% CI 1.26-1.53) in women after adjustment. CONCLUSIONS We found that MetS is a risk factor for CRC in this study. Therefore, the prevention and active management of MetS would contribute to the prevention of CRC.
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Affiliation(s)
- JungHyun Lee
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Kun Sei Lee
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Hyeongsu Kim
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Hyoseon Jeong
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Min-Jung Choi
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Hai-Won Yoo
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Tae-Hwa Han
- Health IT Center, College of Medicine, Yonsei University, Seoul, Korea
| | - Hyunjung Lee
- Department of Nursing, College of Nursing, Konyang University, Daejeon, Korea
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Dodds SG, Parihar M, Javors M, Nie J, Musi N, Dave Sharp Z, Hasty P. Acarbose improved survival for Apc +/Min mice. Aging Cell 2020; 19:e13088. [PMID: 31903726 PMCID: PMC6996958 DOI: 10.1111/acel.13088] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 10/24/2019] [Accepted: 11/17/2019] [Indexed: 12/12/2022] Open
Abstract
Acarbose blocks the digestion of complex carbohydrates, and the NIA Intervention Testing Program (ITP) found that it improved survival when fed to mice. Yet, we do not know if lifespan extension was caused by its effect on metabolism with regard to the soma or cancer suppression. Cancer caused death for ~80% of ITP mice. The ITP found rapamycin, an inhibitor to the pro-growth mTORC1 (mechanistic target of rapamycin complex 1) pathway, improved survival and it suppressed tumors in Apc+/Min mice providing a plausible rationale to ask if acarbose had a similar effect. Apc+/Min is a mouse model prone to intestinal polyposis and a mimic of familial adenomatous polyposis in people. Polyp-associated anemia contributed to their death. To address this knowledge gap, we fed two doses of acarbose to Apc+/Min mice. Acarbose improved median survival at both doses. A cross-sectional analysis was performed next. At both doses, ACA fed mice exhibited reduced intestinal crypt depth, weight loss despite increased food consumption and reduced postprandial blood glucose and plasma insulin, indicative of improved insulin sensitivity. Dose-independent and dose-dependent compensatory liver responses were observed for AMPK and mTORC1 activities, respectively. Only mice fed the high dose diet exhibited reductions in tumor number with higher hematocrits. Because low-dose acarbose improved lifespan but failed to reduced tumors, its effects seem to be independent of cancer. These data implicate the importance of improved carbohydrate metabolism on survival.
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Affiliation(s)
- Sherry G. Dodds
- Department of Molecular Medicine and Institute of BiotechnologyUniversity of Texas HealthSan AntonioTXUSA
| | - Manish Parihar
- Department of Molecular Medicine and Institute of BiotechnologyUniversity of Texas HealthSan AntonioTXUSA
| | - Martin Javors
- Department of PsychiatryUniversity of Texas HealthSan AntonioTXUSA
| | - Jia Nie
- Barshop Institute for Longevity and Aging StudiesUniversity of Texas HealthSan AntonioTXUSA
| | - Nicolas Musi
- Barshop Institute for Longevity and Aging StudiesUniversity of Texas HealthSan AntonioTXUSA
- San Antonio Geriatric ResearchEducation, and Clinical CenterSouth Texas Veterans Health Care SystemSan AntonioTXUSA
| | - Zelton Dave Sharp
- Department of Molecular Medicine and Institute of BiotechnologyUniversity of Texas HealthSan AntonioTXUSA
- Barshop Institute for Longevity and Aging StudiesUniversity of Texas HealthSan AntonioTXUSA
- Mays Cancer CenterUniversity of Texas HealthSan AntonioTXUSA
| | - Paul Hasty
- Department of Molecular Medicine and Institute of BiotechnologyUniversity of Texas HealthSan AntonioTXUSA
- Barshop Institute for Longevity and Aging StudiesUniversity of Texas HealthSan AntonioTXUSA
- Mays Cancer CenterUniversity of Texas HealthSan AntonioTXUSA
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Li X, Zhang K, Hu Y, Luo N. ERRα activates SHMT2 transcription to enhance the resistance of breast cancer to lapatinib via modulating the mitochondrial metabolic adaption. Biosci Rep 2020; 40:BSR20192465. [PMID: 31894856 PMCID: PMC6970080 DOI: 10.1042/bsr20192465] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 12/24/2019] [Accepted: 12/27/2019] [Indexed: 12/14/2022] Open
Abstract
Lapatinib, a tyrosine kinase inhibitor, can initially benefit the patients with breast tumors but fails in later treatment due to the inevitable development of drug resistance. Estrogen-related receptor α (ERRα) modulates the metabolic adaptations in lapatinib-resistant cancer cells; however, the underlying mechanism remains unclear. ERRα was predicted to bind to the serine hydroxymethyltransferase 2 (SHMT2) transcription initiation site in the ER- and HER2-positive cell line BT-474; thus, we hypothesize that ERRα might modulate the resistance of breast cancer to lapatinib via regulating SHMT2. In the present study, we revealed that 2.5 and 5 µM lapatinib treatment could significantly decrease the expression and protein levels of ERRα and SHMT2; ERRα and SHMT2 expression and protein levels were significantly up-regulated in breast cancer cells, in particularly in breast cancer cells with resistance to lapatinib. ERRα knockdown restored the inhibitory effects of lapatinib on the BT-474R cell viability and migration; in the meantime, ERRα knockdown rescued the production of reactive oxygen species (ROS) whereas decreased the ratio of glutathione (GSH)/oxidized glutathione (GSSG) upon lapatinib treatment. Via targeting SHMT2 promoter region, ERRα activated the transcription of SHMT2. The effects of ERRα knockdown on BT-474R cells under lapatinib treatment could be significantly reversed by SHMT2 overexpression. In conclusion, ERRα knockdown suppresses the detoxification and the mitochondrial metabolic adaption in breast cancer resistant to lapatinib; ERRα activates SHMT2 transcription via targeting its promoter region, therefore enhancing breast cancer resistance to lapatinib.
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Affiliation(s)
- Xin Li
- Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Kejing Zhang
- Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yu Hu
- Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Na Luo
- Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
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Sueta D, Tabata N, Ikeda S, Saito Y, Ozaki K, Sakata K, Matsumura T, Yamamoto-Ibusuki M, Murakami Y, Jodai T, Fukushima S, Yoshida N, Kamba T, Araki E, Iwase H, Fujii K, Ihn H, Kobayashi Y, Minamino T, Yamagishi M, Maemura K, Baba H, Matsui K, Tsujita K. Differential predictive factors for cardiovascular events in patients with or without cancer history. Medicine (Baltimore) 2019; 98:e17602. [PMID: 31689764 PMCID: PMC6946347 DOI: 10.1097/md.0000000000017602] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 09/16/2019] [Accepted: 09/19/2019] [Indexed: 11/25/2022] Open
Abstract
Although attention has been paid to the relationship between malignant diseases and cardiovascular diseases, few data have been reported. Moreover, there have also been few reports in which the preventive factors were examined in patients with or without malignant disease histories requiring percutaneous coronary intervention (PCI).This was a retrospective, single-center, observational study. A total of 1003 post-PCI patients were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and admission due to heart failure within 5 years of PCI. Kaplan-Meier analysis showed a significantly higher probability of the primary endpoint in the malignant group (P = .002). Multivariable Cox hazard analyses showed that in patients without a history of malignant, body mass index (BMI) and the presence of dyslipidemia were independent and significant negative predictors of the primary endpoint (BMI: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.53-0.99, P = .041; prevalence of dyslipidemia: HR 0.72, 95% CI 0.52-0.99, P = .048), and the presence of multi-vessel disease (MVD) and the prevalence of peripheral artery disease (PAD) were independent and significant positive predictors of the primary endpoint (prevalence of MVD: HR 1.68, 95% CI 1.18-2.40, P = .004; prevalence of PAD: HR 1.51, 95% CI 1.03-2.21, P = .034). In patients with histories of malignancy, no significant independent predictive factors were identified.Patients undergoing PCI with malignancy had significantly higher rates of adverse cardiovascular events but might not have the conventional prognostic factors.
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Affiliation(s)
- Daisuke Sueta
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences
- Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto
| | - Noriaki Tabata
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences
- Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto
| | - Satoshi Ikeda
- Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki
| | - Yuichi Saito
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba
| | - Kazuyuki Ozaki
- Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata
| | - Kenji Sakata
- Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa
| | - Takeshi Matsumura
- Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto
- Department of Metabolic Medicine, Faculty of Life Sciences
| | | | | | - Takayuki Jodai
- Department of Respiratory Medicine, Graduate School of Medical Sciences
| | - Satoshi Fukushima
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences
- Division of Translational Research and Advanced Treatment Against Gastrointestinal Cancer
| | | | - Eiichi Araki
- Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto
- Department of Metabolic Medicine, Faculty of Life Sciences
| | - Hirotaka Iwase
- Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences
| | - Kazuhiko Fujii
- Department of Respiratory Medicine, Graduate School of Medical Sciences
| | - Hironobu Ihn
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences
| | - Yoshio Kobayashi
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba
| | - Tohru Minamino
- Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata
| | - Masakazu Yamagishi
- Department of Cardiovascular and Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa
| | - Koji Maemura
- Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki
| | - Hideo Baba
- Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences
| | - Kunihiko Matsui
- Community, Family, and General Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences
- Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto
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Li X, Chen H, Wang G, Feng X, Lyu Z, Wei L, Wen Y, Chen S, Wu S, Hang D, Dai M, Li N, He J. Metabolic Syndrome Components and the Risk of Colorectal Cancer: A Population-Based Prospective Study in Chinese Men. Front Oncol 2019; 9:1047. [PMID: 31681585 PMCID: PMC6811600 DOI: 10.3389/fonc.2019.01047] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 09/26/2019] [Indexed: 12/18/2022] Open
Abstract
Background: To investigate the association between metabolic syndrome (MetS) and the risk of colorectal cancer (CRC) in Chinese men, this study was performed based on data from a large prospective cohort study conducted in China named the Kailuan men cohort study. Methods : A total of 104,333 eligible men who participated in biennial examinations at least once from 2006 to 2015 were recruited. Cox proportional hazards regression models were used to estimate the effects of MetS components on CRC risk. Results: During an 824,211.96 person-years follow-up, 394 CRC cases were verified. Participants with high waist circumference (≥90 vs. <90 cm) had a significantly higher risk of developing incident CRC (HR = 1.32, 95% CI: 1.07–1.64). Compared with participants with no MetS components, the HRs (95% CI) of developing CRC for men with 1, 2, and ≥3 MetS components were 1.53 (1.01–2.32), 1.42 (0.94–2.14), and 1.70 (1.12–2.56), respectively. In addition, a statistically significant trend (P for trend =0.04) of increased CRC risk with an increasing number of abnormal MetS components was observed. Furthermore, compared with no MetS components, the combination of high waist circumference and elevated fasting blood glucose along with normal levels of the other 3 components, showed a 126% increased risk of CRC. Conclusions: Our study suggests that CRC risk is correlated with the number of abnormal MetS components in Chinese men. Men with high waist circumference and elevated fasting blood glucose may have a higher CRC risk even if they do not meet the MetS diagnostic criteria.
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Affiliation(s)
- Xin Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongda Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gang Wang
- Department of Oncology, Kailuan General Hospital, Tangshan, China
| | - Xiaoshuang Feng
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhangyan Lyu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Luopei Wei
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Wen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuohua Chen
- Health Department of Kailuan (Group), Tangshan, China
| | - Shouling Wu
- Health Department of Kailuan (Group), Tangshan, China
| | - Dong Hang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Min Dai
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ni Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie He
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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50
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Murdocca M, Capuano R, Pucci S, Cicconi R, Polidoro C, Catini A, Martinelli E, Paolesse R, Orlandi A, Mango R, Novelli G, Di Natale C, Sangiuolo F. Targeting LOX-1 Inhibits Colorectal Cancer Metastasis in an Animal Model. Front Oncol 2019; 9:927. [PMID: 31608230 PMCID: PMC6761277 DOI: 10.3389/fonc.2019.00927] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 09/04/2019] [Indexed: 12/31/2022] Open
Abstract
Recurrence and metastasis are the primary causes of mortality in patients with colorectal cancer (CRC), and therefore effective tools to reduce morbidity and mortality of CRC patients are necessary. LOX-1, the ox-LDL receptor, is strongly involved in inflammation, obesity, and atherosclerosis, and several studies have assessed its role in the carcinogenesis process linking ROS, metabolic disorders and cancer. We have already demonstrated in vitro that LOX-1 expression correlates to the aggressiveness of human colon cancer and its downregulation weakens the tumoral phenotype, indicating its potential function as a biomarker and a target in CRC therapy. Here we further investigate in vivo the role of LOX-1 in colon tumorigenesis by xenografting procedures, injecting nude mice both subcutaneously and intravenously with human high grade metastatic colorectal cancer cells, DLD-1, in which LOX-1 expression has been downregulated by shRNA (LOX-1RNAi cells). Histopathological and immunohistochemical evaluations have been performed on xenograft tumors. The experiments have been complemented by the analysis of the volatile compounds (VOCs) collected from the cages of injected mice and analyzed by gas-chromatography and gas sensors. After intravenous injection of LOX-1RNAi cells, we found that LOX-1 silencing influences both the engraftment of the tumor and the metastasis development, acting by angiogenesis. For the first time, we have observed that LOX-1 inhibition significantly prevents metastasis formation in injected mice and, at the same time, induces a downregulation of VEGF-A165, HIF-1α, and β-catenin whose expression is involved in cell migration and metastasis, and a variation of histone H4 acetylation pattern suggesting also a role of LOX-1 in regulating gene transcription. The analysis of the volatile compounds (VOCs) collected from the cages of injected mice has evidenced a specific profile in those xenograft mice in which metastasis originates. These findings underline the role of LOX-1 as a potential target for inhibition of tumor progression and metastasis, enhancing current therapeutic strategies against colorectal cancer.
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Affiliation(s)
- Michela Murdocca
- Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
| | - Rosamaria Capuano
- Department of Electronic Engineering, Tor Vergata University, Rome, Italy
| | - Sabina Pucci
- Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
| | - Rosella Cicconi
- Centro Servizi Interdipartimentale STA, Tor Vergata University, Rome, Italy
| | - Chiara Polidoro
- Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
| | - Alexandro Catini
- Department of Electronic Engineering, Tor Vergata University, Rome, Italy
| | - Eugenio Martinelli
- Department of Electronic Engineering, Tor Vergata University, Rome, Italy
| | - Roberto Paolesse
- Department of Chemical Science and Technology, Tor Vergata University, Rome, Italy
| | - Augusto Orlandi
- Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
| | - Ruggiero Mango
- Cardiology Unit, Department of Emergency and Critical Care, Policlinic of Tor Vergata, Rome, Italy
| | - Giuseppe Novelli
- Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
| | - Corrado Di Natale
- Department of Electronic Engineering, Tor Vergata University, Rome, Italy
| | - Federica Sangiuolo
- Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy
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