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Shahrivar M, Dietrich CE, Glimelius B, Saraste D, Martling A, Buchli C, Nordenvall C. Type II diabetes and metformin use does not affect colorectal cancer prognosis. Int J Cancer 2025; 156:1736-1745. [PMID: 39600254 PMCID: PMC11887022 DOI: 10.1002/ijc.35266] [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: 08/29/2024] [Revised: 10/28/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
Previous studies on the impact of metformin and colorectal cancer (CRC) outcomes have been limited by small size and confounding by indication, yielding inconsistent results. The aim of this study was to assess whether diabetes and pre-diagnostic metformin use influence CRC prognosis. The study was performed using the Colorectal Cancer Data Base Sweden, a register-linkage originating from the Swedish Colorectal Cancer Register with linkage to national health care registers and demographic registers. All adult patients diagnosed with primary non-metastatic CRC between 2007 and 2016, treated with curative surgery, were identified and followed up from 90 days post-surgery until December 31, 2022. Antidiabetic medication use was defined as dispensed prescription ≥6 months of use within 1 year of surgery. Type II diabetes mellitus (T2DM) patients were divided into three treatment groups (i) diet only, (ii) metformin user, and (iii) non-metformin user. Cox regression models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for time to recurrence, CRC-specific, and all-cause mortality, adjusted for relevant covariates. Of 33,028 non-metastatic CRC patients, 4539 (13.7%) had T2DM, with 1745 using metformin. A T2DM diagnosis was not associated with increased recurrence rate or CRC-specific mortality; HRadj 0.97 (95% CI 0.89-1.06) and HRadj 0.95 (95% CI 0.87-1.05), respectively, compared with non-diabetic patients. Furthermore, no association between T2DM, metformin use, and recurrence or CRC-specific mortality was seen, HRadj 0.98 (95% CI 0.86-1.12) and HRadj 0.98 (95% CI 0.85-1.13), respectively. T2DM is not associated with an elevated recurrence or CRC-specific mortality. Additionally, metformin use does not impact CRC prognosis.
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Affiliation(s)
- Mehrnoosh Shahrivar
- Department of Molecular Medicine and SurgeryKarolinska InstitutetStockholmSweden
| | - Caroline E. Dietrich
- Clinical Epidemiology Division, Department of Medicine SolnaKarolinska InstitutetStockholmSweden
| | - Bengt Glimelius
- Department of Immunology, Genetics and pathologyUppsala UniversityUppsalaSweden
| | - Deborah Saraste
- Department of Clinical Science and EducationKarolinska InstitutetStockholmSweden
- Department of SurgeryStockholmSweden
| | - Anna Martling
- Department of Molecular Medicine and SurgeryKarolinska InstitutetStockholmSweden
- Department of Pelvic Cancer, GI oncology and colorectal surgery unitKarolinska University HospitalStockholmSweden
| | - Christian Buchli
- Department of Molecular Medicine and SurgeryKarolinska InstitutetStockholmSweden
- Department of Pelvic Cancer, GI oncology and colorectal surgery unitKarolinska University HospitalStockholmSweden
| | - Caroline Nordenvall
- Department of Molecular Medicine and SurgeryKarolinska InstitutetStockholmSweden
- Department of Pelvic Cancer, GI oncology and colorectal surgery unitKarolinska University HospitalStockholmSweden
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Lawler T, Hibler E, Walts ZL, Giurini L, Steinwandel M, Lipworth L, Murff HJ, Zheng W, Warren Andersen S. Associations of diabetes and mortality among colorectal cancer patients from the Southern Community Cohort Study. Br J Cancer 2024; 131:1050-1059. [PMID: 39030444 PMCID: PMC11405675 DOI: 10.1038/s41416-024-02787-4] [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: 11/27/2023] [Revised: 06/25/2024] [Accepted: 07/01/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND We investigated associations between diabetes and mortality among participants with incident colorectal cancer (CRC) from the Southern Community Cohort Study. METHODS Participants (73% non-Hispanic Black; 60% income < $15,000) were recruited between 2002-2009. Diabetes was self-reported at enrollment and follow-up surveys at approximately 5-year intervals. Incident CRC and mortality were identified via state registries and the National Death Index. Proportional hazards models calculated associations between diabetes with overall, CRC-specific mortality among 1059 participants with incident CRC. RESULTS Diabetes prior to diagnosis is associated with elevated overall (hazard ratio [95% confidence interval]: (1.46[1.22-1.75]), and CRC-specific mortality (1.36[1.06-1.74])) after adjustment for tumor stage. For non-Hispanic Black and non-Hispanic White participants, consistent associations were observed for overall (1.35[1.10-1.66] vs. 1.89[1.31-2.72], respectively, p-interaction = 0.11) and CRC-specific mortality (1.30[0.99-1.71] vs. 1.77[1.06-2.95], respectively, p-interaction = 0.28). For individuals with incomes <$15,000/year, associations with overall (1.44[1.15-1.79]) and CRC-specific mortality (1.28[0.94-1.73]) were similar to the full sample. Associations with overall (1.71[1.37-2.13]) and CRC-specific mortality (1.65[1.22-2.22]) were highest for diabetes ≥ 10 years at diagnosis. CONCLUSIONS Pre-diagnosis diabetes is associated with higher mortality among participants with incident CRC from a predominantly non-Hispanic Black cohort with lower socioeconomic status. The higher prevalence of diabetes in this population may contribute to racial disparities in CRC mortality.
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Affiliation(s)
- Thomas Lawler
- University of Wisconsin Carbone Cancer Center, Madison, WI, 53726, USA
| | - Elizabeth Hibler
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Zoe L Walts
- University of Wisconsin Carbone Cancer Center, Madison, WI, 53726, USA
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 610 Walnut St, WARF Office Building, Madison, WI, 53726, USA
| | - Lauren Giurini
- University of Wisconsin Carbone Cancer Center, Madison, WI, 53726, USA
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 610 Walnut St, WARF Office Building, Madison, WI, 53726, USA
| | - Mark Steinwandel
- International Epidemiology Field Station, Vanderbilt Institute for Clinical and Translational Research, 1455 Research Blvd.; Suite 550, Rockville, MD, 20850, USA
| | - Loren Lipworth
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Nashville, TN, 37203-1738, USA
| | - Harvey J Murff
- Department of Medicine, Vanderbilt University School of Medicine, 6012 Medical Center East, 1215 21st Avenue South, Nashville, TN, 37203-1738, USA
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Nashville, TN, 37203-1738, USA
| | - Shaneda Warren Andersen
- University of Wisconsin Carbone Cancer Center, Madison, WI, 53726, USA.
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 610 Walnut St, WARF Office Building, Madison, WI, 53726, USA.
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Nashville, TN, 37203-1738, USA.
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Kumar S, Blandon C, Sikorskii A, Kaplan DE, Mehta SJ, Su GL, Goldberg DS, Crane TE. Investigating the Obesity Paradox in Colorectal Cancer: An Analysis of Prospectively Collected Data in a Diverse Cohort. Cancers (Basel) 2024; 16:2950. [PMID: 39272808 PMCID: PMC11394385 DOI: 10.3390/cancers16172950] [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: 07/17/2024] [Revised: 08/14/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. METHODS Utilizing the Multiethnic Cohort, we included adults aged 18-75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. RESULTS Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00-2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10-2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31-6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08-3.10], p = 0.026). CONCLUSIONS Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis.
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Affiliation(s)
- Shria Kumar
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
- Sylvester Comprehensive Cancer Center, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
| | - Catherine Blandon
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
| | - Alla Sikorskii
- Department of Psychiatry, Michigan State University, East Lansing, MI 48824, USA
| | - David E Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA
| | - Shivan J Mehta
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Grace L Su
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
- Medicine Service, Lieutenant Colonel Charles S. Kettles VA Medical Center, Ann Arbor, MI 48105, USA
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
- Sylvester Comprehensive Cancer Center, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
| | - Tracy E Crane
- Sylvester Comprehensive Cancer Center, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
- Division of Medical Oncology, Department of Medicine, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA
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Pliszka M, Szablewski L. Associations between Diabetes Mellitus and Selected Cancers. Int J Mol Sci 2024; 25:7476. [PMID: 39000583 PMCID: PMC11242587 DOI: 10.3390/ijms25137476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/15/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Cancer is one of the major causes of mortality and is the second leading cause of death. Diabetes mellitus is a serious and growing problem worldwide, and its prevalence continues to grow; it is the 12th leading cause of death. An association between diabetes mellitus and cancer has been suggested for more than 100 years. Diabetes is a common disease diagnosed among patients with cancer, and evidence indicates that approximately 8-18% of patients with cancer have diabetes, with investigations suggesting an association between diabetes and some particular cancers, increasing the risk for developing cancers such as pancreatic, liver, colon, breast, stomach, and a few others. Breast and colorectal cancers have increased from 20% to 30% and there is a 97% increased risk of intrahepatic cholangiocarcinoma or endometrial cancer. On the other hand, a number of cancers and cancer therapies increase the risk of diabetes mellitus. Complications due to diabetes in patients with cancer may influence the choice of cancer therapy. Unfortunately, the mechanisms of the associations between diabetes mellitus and cancer are still unknown. The aim of this review is to summarize the association of diabetes mellitus with selected cancers and update the evidence on the underlying mechanisms of this association.
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Affiliation(s)
- Monika Pliszka
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
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Li F, Wan X, Li Z, Zhou L. High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K/AKT/mTOR pathway. Cancer Med 2024; 13:e7382. [PMID: 38872380 PMCID: PMC11176572 DOI: 10.1002/cam4.7382] [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: 02/25/2024] [Revised: 05/16/2024] [Accepted: 05/28/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, characterized by its complex etiology and slow research progress. Diabetes, as an independent risk factor for CRC, has been widely certified. Consequently, this study centers on elucidating the intricacies of CRC cells initiation and progression within a high-glucose environment. METHODS A battery of assays was employed to assess the proliferation and metastasis of CRC cells cultured under varying glucose concentrations. Optimal glucose levels conducive to cells' proliferation and migration were identified. Western blot analyses were conducted to evaluate alterations in apoptosis, autophagy, and EMT-related proteins in CRC cells under high-glucose conditions. The expression of PI3K/AKT/mTOR pathway-associated proteins was assessed using western blot. The effect of high glucose on xenograft growth was investigated in vivo by MC38 cells, and changes in inflammatory factors (IL-4, IL-13, TNF-α, IL-5, and IL-12) were measured via serum ELISA. RESULTS Our experiments demonstrated that elevated glucose concentrations promoted both the proliferation and migration of CRC cells; the most favorable glucose dose is 20 mM. Western blot analyses revealed a decrease in apoptotic proteins, such as Bim, Bax, and caspase-3 with increasing glucose levels. Concurrently, the expression of EMT-related proteins, including N-cadherin, vimentin, ZEB1, and MMP9, increased. High-glucose cultured cells exhibited elevated levels of PI3K/AKT/mTOR pathway proteins. In the xenograft model, tumor cells stimulated by high glucose exhibited accelerated growth, larger tumor volumes, and heightened KI67 expression of immunohistochemistry. ELISA experiments revealed higher expression of IL-4 and IL-13 and lower expression of TNF-α and IL-5 in the serum of high-glucose-stimulated mice. CONCLUSION The most favorable dose and time for tumor cells proliferation and migration is 20 mM, 48 h. High glucose fosters CRC cell proliferation and migration while suppressing autophagy through the activation of the PI3K/AKT/mTOR pathway.
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Affiliation(s)
- Feng Li
- Department of Pharmacology, West China School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, China
| | - Xing Wan
- Department of Pharmacology, West China School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, China
| | - Zhigui Li
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Liming Zhou
- Department of Pharmacology, West China School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, China
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Elabd NS, Alabassy MM, Seddik RM, Amer AA, Abdelaziz RA, Sohaib A. Type 2 Diabetes Mellitus and Non-Metastatic Colorectal Cancer: A Retrospective Study on Survival and Toxicity Profiles. Asian Pac J Cancer Prev 2024; 25:87-94. [PMID: 38285771 PMCID: PMC10911739 DOI: 10.31557/apjcp.2024.25.1.87] [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: 05/17/2023] [Accepted: 01/22/2024] [Indexed: 01/31/2024] Open
Abstract
BACKGROUND AND AIMS Being one of the most common cancers accounting for approximately 185 million cases globally, colorectal cancer (CRC) is one of the leading derivers of cancer-related mortalities. A high prevalence of Type 2 diabetes mellitus and CRC was noted, together with a causal link between diabetes and CRC development. Thereby, the goal of this study was to properly evaluate type 2 Diabetes mellitus in non-metastatic colorectal cancer patients, and to highlight its impacts on patient's outcome. METHODS Patients with non-metastatic colorectal cancer diagnosed between January 2016 and December 2020 were studied retrospectively. Patients were divided into two groups based on whether or not they had type II diabetes. The clinico-pathological, laboratory, treatment and survival data were gathered. RESULTS A total of 318 patients were included in this study. The toxicity of the drugs used in CRC patients receiving the treatment protocols (169 in non-T2DM group and 39 in T2DM group), both groups reported close percentage of side effects and a similar frequency of drug toxicity occurrence as well as grade of toxicity, with the exception of neuropathy, which was more common in the T2DM group (33.3% vs 11.2%). As for prognosis, non-T2DM and T2DM patients had a mean progression free survival of (71.4 and 60.83 months, respectively) (p = 0.019). Overall survival was 73.1% for T2DM and 85.3% for non T2DM cases. The median overall survival was not reached for both groups in terms of overall survival. CONCLUSION T2DM is considered a risk factor for poor survival among CRC patients. Treatment related toxicity is not affected by the presence or absence of diabetes, yet neuropathy needs further studies for diabetic patients receiving oxaliplatin.
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Affiliation(s)
- Naglaa Said Elabd
- Tropical Medicine department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt.
| | - Mahmoud Magdy Alabassy
- General surgery department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt.
| | - Randa Mohamed Seddik
- Tropical Medicine department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt.
| | - Amany A. Amer
- Tropical Medicine department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt.
| | - Reham Ahmed Abdelaziz
- Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt.
| | - Ahmed Sohaib
- Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt.
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Herold M, Szasz AM, Szentmartoni G, Martinek E, Madar-Dank V, Barna AJ, Mohacsi R, Somogyi A, Dank M, Herold Z. Influence of the duration of type 2 diabetes mellitus on colorectal cancer outcomes. Sci Rep 2023; 13:12985. [PMID: 37563292 PMCID: PMC10415401 DOI: 10.1038/s41598-023-40216-3] [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: 05/03/2023] [Accepted: 08/07/2023] [Indexed: 08/12/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive disease, which affects colorectal cancer (CRC) survival. However, data on the relationship between CRC survival and T2DM duration is scarce and controversial. A retrospective observational study was conducted. Sub-cohorts were created based on the duration of T2DM as follows, ≤ or > 5/10/15/20 years. 204 of the 817 (24.95%) included study participants had T2DM at any point of CRC. 160 of the 204 CRC + T2DM patients had detailed T2DM duration data. At the time of CRC diagnosis, 85, 50, 31, and 11 patients had T2DM for > 5/10/15/20 years, respectively, which increased to 110, 71, 45, and 17 during the course of the study. Despite constant glycated hemoglobin values throughout the study, shorter overall and disease-specific survival times were observed for the > 5/10/15 years cohorts and longitudinal survival modeling techniques confirmed the significant effect of T2DM duration in all cohorts. While in the first 3 years after CRC diagnosis, the best survival was found for the ≤ 5 years cohort, all diabetes cohorts had the same survival thereafter. T2DM duration affected CRC survival significantly, therefore, a closer follow-up of this sub-populations is suggested.
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Affiliation(s)
- Magdolna Herold
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, 1088, Hungary
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Gyongyver Szentmartoni
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Emoke Martinek
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Viktor Madar-Dank
- Department of the Institute for Dispute Resolution, New Jersey City University, Jersey City, NJ, 07311, USA
| | - Andras Jozsef Barna
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
- Department of Obstetrics and Gynecology, Saint Pantaleon Hospital, Dunaujvaros, 2400, Hungary
| | - Reka Mohacsi
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Aniko Somogyi
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest, 1088, Hungary
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary
| | - Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, 1083, Hungary.
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Liu D, Zhang X, Zhou H, Zhu Z, He Y, Wan X, Zhang B, Liu S, Liu L. Marked paper: Type 2 diabetes mellitus indicates increased postoperative complications and poor prognosis in colorectal cancer patients receiving curative surgery. Front Oncol 2023; 13:1128383. [PMID: 36845740 PMCID: PMC9947490 DOI: 10.3389/fonc.2023.1128383] [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: 12/20/2022] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
Purpose This study aimed to evaluate the impact of type 2 diabetes mellitus (T2DM) on the short-term outcomes and long-term survival of patients with colorectal cancer (CRC) who underwent curative resection. Methods This study retrospectively included 136 patients (T2DM group) with resectable CRC and T2DM from Jan 2013 to Dec 2017. Propensity score-matched control group consisting of 136 patients (non-T2DM group) were selected from 1143 CRC patients without T2DM. The short-term outcomes and prognosis were compared between the T2DM and non-T2DM group. Results A total of 272 patients (136 patients for each group) were included in this study. Patients in T2DM group had higher body mass index (BMI), higher proportion of hypertension and cerebrovascular diseases (P<0.05). T2DM group had more overall complications (P=0.001), more major complications (P=0.003) and higher risk of reoperation (P=0.007) when compared with non-T2DM patients. T2DM patients had longer hospitalization time than non-T2DM (20.7 ± 10.2 vs. 17.5 ± 6.2, P=0.002). As for the prognosis, T2DM patients had worse 5-year overall survival (OS) (P=0.024) and 5-year disease-free survival (DFS) (P=0.019) in all stage. Moreover, T2DM and TNM stage were the independent predictors of OS and DFS for CRC patients. Conclusions T2DM increases overall complications and major complications, and prolongs the hospitalization time after CRC surgery. In addition, T2DM indicates the poor prognosis of CRC patients. A prospective study with large sample size is required to confirm our findings.
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Affiliation(s)
- Daoli Liu
- Department of Gastrointestinal Surgery, Anqing First People’s Hospital of Anhui Medical University, An Qing, An Hui, China
| | - Xubing Zhang
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Hong Zhou
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Zhiqiang Zhu
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Yiren He
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Xiao Wan
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Bo Zhang
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Shaojun Liu
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,*Correspondence: Shaojun Liu, ; Liu Liu,
| | - Liu Liu
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China,Department of General Surgery, The Anhui Provincial Hospital affiliated to the An Hui Medical University, He Fei, An Hui, China,*Correspondence: Shaojun Liu, ; Liu Liu,
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9
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Meng Q, Yu Y, Wang K, Zhang Z, Zhao J, Wang Y, Hao D, Wang G. The prognostic role of fasting plasma glucose levels on survival in advanced colorectal cancer patients with type II diabetes mellitus: a retrospective cohort study. J Gastrointest Oncol 2022; 13:3080-3089. [PMID: 36636046 PMCID: PMC9830360 DOI: 10.21037/jgo-22-1124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022] Open
Abstract
Background Previous studies have shown that type II diabetes mellitus (T2DM) has a significant effect on the occurrence and development of colorectal cancer (CRC). The associations between fasting plasma glucose (FPG) and overall survival (OS) of CRC patients with T2DM are still controversial. The present study sought to examine the association between FPG control and OS in advanced CRC patients with T2DM. Methods The data of advanced CRC patients with T2DM who were admitted to Harbin Medical University Cancer Hospital from May 2010 to May 2019 were retrospectively collected and examined. Record patient clinical data including age, sex, blood pressure, body mass index (BMI), primary tumor site, T stage, N stage, histological grade, number of metastatic sites, primary tumor surgery, etc. The baseline FPG which was measured before the first-line treatment and the FPG measured before each admission treatment during advanced chemotherapy were collected. OS was determined as the end point of the study. All the patients were followed-up for at least 3 years. The Kaplan-Meier log-rank method and the Cox proportional hazards regression analyses were used for the analysis of OS and hazard factors. Results A total of 210 patients met the inclusion criteria for the study, who had a median age of 66.5 years; 94 patients had baseline FPG levels ≤7 mmol/L, and 116 patients had baseline FPG levels >7 mmol/L. Compared to the baseline FPG >7 mmol/L group, the OS of patients in the baseline FPG ≤7 mmol/L group was not significantly prolonged (P=0.88). There were 52 patients in the FPG-A group and 61 in the FPG-B group. Similarly, there was no significant difference in OS between the FPG-A and FPG-B groups (P=0.96). The N0 stage subgroup analysis showed that glycemic control ≤7 mmol/L resulted in longer OS. Conclusions The results of the present study showed that FPG levels may not affect the survival of advanced CRC patients with T2DM. However, this needs multicenter prospective studies to confirm.
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Affiliation(s)
- Qianhao Meng
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuanyuan Yu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Ke Wang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Zicheng Zhang
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China
| | - Jian Zhao
- Department of Digestive, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Yusheng Wang
- Department of Digestive, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Dapeng Hao
- Department of Pathology, Harbin Medical University, Harbin, China
| | - Guangyu Wang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
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10
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Impact of Diabetes on Short-Term and Long-Term Outcomes of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy. Curr Oncol 2022; 29:6724-6734. [PMID: 36290805 PMCID: PMC9600143 DOI: 10.3390/curroncol29100528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/07/2022] [Accepted: 09/14/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Many studies have confirmed that diabetes was associated with prognosis in many malignant cancer types. However, the impact of diabetes on ampullary carcinoma (AC) has not been investigated. METHODS A total of 266 AC patients in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. The postoperative complication rate, postoperative recurrence rate, and long-term survival were compared between the diabetes group and the no diabetes group. RESULTS A total of 32 AC patients (12.03%) were diagnosed with diabetes before surgery. In total, 111 patients (41.73%) had one or more postoperative complications, and there was no perioperative death. There was no statistically significant difference regarding postoperative complications between the diabetes group and the no diabetes group. Altogether, 120 patients (45.11%) experienced postoperative recurrence. Multivariate analysis revealed that diabetes was an independent risk factor for the recurrence (OR: 2.384, 95% CI: 1.065-5.336, p = 0.035), OS (HR: 1.597, 95% CI: 1.005-2.537, p = 0.047), and RFS (HR: 1.768, 95% CI: 1.068-2.925, p = 0.027) in AC patients after curative pancreatoduodenectomy. CONCLUSIONS Diabetes may adversely affect the recurrence of patients with AC after curative pancreaticoduodenectomy, leading to an increased risk of poor prognosis in early-stage patients. Further studies involving a large sample size are needed to validate our results.
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11
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Hoyos-Valdelamar JC, Lora-Acuña LJ, Herrera-Zabaleta LE, Parra-Almeida S, Insignares-Farak Y. Caracterización del cáncer colorrectal en pacientes atendidos en un centro médico del caribe colombiano. REVISTA COLOMBIANA DE CIRUGÍA 2022. [DOI: 10.30944/20117582.2124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Introducción. A nivel mundial el cáncer colorrectal es la tercera causa de malignidad y la segunda causa de mortalidad por cáncer. En Colombia, tiene una prevalencia de 8,3 % dentro de las patologías neoplásicas, ubicándolo en el tercer lugar, después del cáncer de próstata y de mama, lo que lo cataloga como un problema de salud pública, por lo que es de gran importancia mantener datos actualizados acerca de su perfil epidemiológico.
Métodos. Se realizó un estudio transversal en pacientes con cáncer colorrectal atendidos en el Hospital Universitario del Caribe, Cartagena, Colombia, durante el periodo 2015-2019. Se analizaron las variables sociodemográficas, clínicas, patológicas e histológicas.
Resultados. Se encontraron un total de 268 pacientes atendidos por cáncer colorrectal, con predominio femenino en el (54,5 %) de los casos, y edad promedio de 62 años; con comorbilidades en 48,8 % y sintomatología de dolor abdominal en 56,7 %. El adenocarcinoma se encontró en el 82,1 % de los casos y la intervención más realizada fue la hemicolectomía derecha.
Conclusión. El perfil epidemiológico del cáncer colorrectal encontrado en este estudio concuerda con los hallazgos de la literatura médica mundial, comprometiendo especialmente mujeres en nuestra institución.
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12
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Harmon BE, Shvetsov YB, Lim U, Leak CL, San Diego ERN, Monroe KR, Wilkens LR, Marchand LL. The joint association of cardiometabolic health and weight on mortality in the multiethnic cohort. ETHNICITY & HEALTH 2022; 27:658-671. [PMID: 32508127 PMCID: PMC7719582 DOI: 10.1080/13557858.2020.1771680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 05/14/2020] [Indexed: 06/11/2023]
Abstract
Objective: While cardiometabolic abnormalities are associated with elevated risk of morbidity, they may not occur in all individuals with obesity. Less is known about associations with mortality, especially cancer mortality. This study examined associations between cardiometabolic-weight categories and mortality from cardiovascular disease (CVD), cancer, and all causes.Methods: Cox proportional hazards regressions of time to all-cause, CVD, and cancer mortalities were used to examine associations with cardiometabolic-weight status, in the Multiethnic Cohort (n=157,865). Cardiometabolic-weight status categories were: Metabolically Healthy Normal Weight, Metabolically Healthy Obese, Metabolically Healthy Overweight, Metabolically Unhealthy Normal Weight, Metabolically Unhealthy Obese, and Metabolically Unhealthy Overweight.Results: Higher mortality, especially for all-cause and CVD, was found for all metabolically unhealthy groups no matter the weight classification when compared to the Metabolically Healthy Normal Weight category across sex-ethnic groups. For all-cause mortality, a reduction in mortality was seen for males in the Metabolically Healthy Overweight category (HR: 0.88, 95% CI: 0.84, 0.93), especially for African American, Native Hawaiian, and Latino males. Mortality was elevated in the Metabolically Healthy Obese category for all-cause and CVD mortality in both sexes (HRrange: 1.08-1.93). Few associations were seen with cancer mortality.Conclusions: Past examinations of cardiometabolic-weight status and mortality have been hampered by a lack of diversity. In a racially/ethnically diverse population, metabolically unhealthy groups exhibited a substantially higher risk of death from all causes and CVD than metabolically healthy groups. A reduction in all-cause mortality was seen for some males classified as Metabolically Healthy Overweight; however, being classified as Metabolically Healthy Obese elevated mortality risk for males and females compared to Metabolically Healthy Normal Weight. Future research is needed to examine how sex-ethnic differences in body fat distribution and changes in weight over time influence associations between cardiometabolic-weight status and mortality.
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Affiliation(s)
- Brook E Harmon
- Division of Social and Behavioral Sciences, School of Public Health, University of Memphis, Memphis, TN, USA
| | - Yurii B Shvetsov
- Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, Manoa, HI, USA
| | - Unhee Lim
- Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, Manoa, HI, USA
| | - Cardella L Leak
- Center for Health System Improvement, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Emily Rose N San Diego
- Division of Social and Behavioral Sciences, School of Public Health, University of Memphis, Memphis, TN, USA
| | - Kristine R Monroe
- Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA
| | - Lynne R Wilkens
- Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, Manoa, HI, USA
| | - Loic Le Marchand
- Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center, Manoa, HI, USA
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13
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Cheng Y, Cheng YX, Liu XY, Kang B, Tao W, Peng D. The Effect of Type 2 Diabetes Mellitus on the Short-Term Outcomes and Prognosis of Stage I–III Colorectal Cancer: A Propensity Score Matching Analysis. Cancer Manag Res 2022; 14:205-214. [PMID: 35046727 PMCID: PMC8763209 DOI: 10.2147/cmar.s347242] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 12/30/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose The purpose of the current study was to analyze the effect of type 2 diabetes mellitus (T2DM) on the short-term outcomes and prognosis of stage I–III colorectal cancer (CRC) undergoing primary surgery. Methods Patients who underwent primary CRC surgery were retrospectively collected from Jan 2011 to Jan 2020 in a single clinical center. The short-term outcomes and prognosis were compared between T2DM group and non-T2DM group using propensity score matching (PSM) analysis. Results A total of 4250 patients were included in this study. There were 521 patients with T2DM and 3729 patients without T2DM. After 1:1 ratio PSM, there were 519 T2DM patients and 519 non-T2DM patients left in this study. No significant difference was found in baseline information after PSM (p>0.05). T2DM had higher overall complications (p=0.033) after PSM in terms of short-term outcomes. As for prognosis, T2DM group had worse overall survival (OS) in all stages (p=0.044), stage I (p=0.009) and stage II (p=0.021) of CRC and T2DM group had worse disease-free survival (DFS) than non-T2DM group in stage I (p=0.008) of CRC before PSM. However, T2DM did not affect the overall survival (OS) or disease-free survival (DFS) on different stages of CRC after PSM (p>0.05). Moreover, T2DM was not an independent predictor of OS or DFS (p>0.05). Conclusion T2DM increased overall complications after primary CRC surgery. However, T2DM might not affect OS and DFS of stage I–III CRC patients.
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Affiliation(s)
- Yong Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Yu-Xi Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Xiao-Yu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Bing Kang
- Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Wei Tao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Dong Peng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
- Correspondence: Dong Peng Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaTel +86 23 89011014 Email
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Ottaiano A, Circelli L, Santorsola M, Savarese G, Fontanella D, Gigantino V, Di Mauro A, Capuozzo M, Zappavigna S, Lombardi A, Perri F, Cascella M, Granata V, Capuozzo M, Nasti G, Caraglia M. Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions. Mol Oncol 2022; 16:319-332. [PMID: 34668636 PMCID: PMC8763648 DOI: 10.1002/1878-0261.13122] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/04/2021] [Accepted: 10/19/2021] [Indexed: 12/13/2022] Open
Abstract
The present study was undertaken to analyze prognostic and genetic interactions between type 2 diabetes and metastatic colorectal cancer. Patients' survival was depicted through the Kaplan-Meier product limit method. Prognostic factors were examined through the Cox proportional-hazards regression model, and associations between diabetes and clinical-pathologic variables were evaluated by the χ2 test. In total, 203 metastatic colorectal cancer patients were enrolled. Lymph nodes (P = 0.0004) and distant organs (> 2 distant sites, P = 0.0451) were more frequently involved in diabetic patients compared with those without diabetes. Diabetes had an independent statistically significant negative prognostic value for survival. Highly selected patients with cancer and/or diabetes as their only illness(es) were divided into three groups: (a) seven oligo-metastatic patients without diabetes, (b) 10 poly-metastatic patients without diabetes, and (c) 12 poly-metastatic diabetic patients. These groups of patients were genetically characterized through the Illumina NovaSeq 6000 (San Diego, CA, USA) platform and TruSigt™Oncology 500 kit, focusing on genes involved in diabetes and colorectal cancer. Gene variants associated with diabetes and cancer were more frequent in patients in group 3. We found that type 2 diabetes is a negative prognostic factor for survival in colorectal cancer. Diabetes-associated gene variants could concur with malignancy, providing a rational basis for innovative models of tumor progression and therapy.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Silvia Zappavigna
- Department of Precision MedicineUniversity “L. Vanvitelli” of NaplesItaly
- Cytometric and Mutational DiagnosticsAzienda Universitaria Policlinico “L. Vanvitelli,”NaplesItaly
| | - Angela Lombardi
- Department of Precision MedicineUniversity “L. Vanvitelli” of NaplesItaly
- Cytometric and Mutational DiagnosticsAzienda Universitaria Policlinico “L. Vanvitelli,”NaplesItaly
| | - Francesco Perri
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale,”NaplesItaly
| | - Marco Cascella
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale,”NaplesItaly
| | - Vincenza Granata
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale,”NaplesItaly
| | | | - Guglielmo Nasti
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale,”NaplesItaly
| | - Michele Caraglia
- Department of Precision MedicineUniversity “L. Vanvitelli” of NaplesItaly
- Cytometric and Mutational DiagnosticsAzienda Universitaria Policlinico “L. Vanvitelli,”NaplesItaly
- Laboratory of Precision and Molecular OncologyBiogem ScarlInstitute of Genetic ResearchAriano IrpinoItaly
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15
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Yuan C, Zhang X, Babic A, Morales-Oyarvide V, Zhang Y, Smith-Warner SA, Wu K, Wang M, Wolpin BM, Meyerhardt JA, Chan AT, Hu FB, Fuchs CS, Ogino S, Giovannucci EL, Ng K. Preexisting Type 2 Diabetes and Survival among Patients with Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 2021; 30:757-764. [PMID: 33531435 PMCID: PMC8026573 DOI: 10.1158/1055-9965.epi-20-1083] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 10/26/2020] [Accepted: 01/15/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Type 2 diabetes increases risk of developing colorectal cancer, but the association of preexisting diabetes with colorectal cancer survival remains unclear. METHODS We analyzed survival by diabetes status at cancer diagnosis among 4,038 patients with colorectal cancer from two prospective U.S. cohorts. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CI) for overall and cause-specific mortality, with adjustment for tumor characteristics and lifestyle factors. RESULTS In the first 5 years after colorectal cancer diagnosis, diabetes was associated with a modest increase in overall mortality in women (HR, 1.22; 95% CI, 1.00-1.49), but not in men (HR, 0.83; 95% CI, 0.62-1.12; P heterogeneity by sex = 0.04). Beyond 5 years, diabetes was associated with substantially increased overall mortality with no evidence of sex heterogeneity; in women and men combined, the HRs were 1.45 (95% CI, 1.09-1.93) during >5-10 years and 2.58 (95% CI, 1.91-3.50) during >10 years. Compared with those without diabetes, patients with colorectal cancer and diabetes had increased mortality from other malignancies (HR, 1.78; 95% CI, 1.18-2.67) and cardiovascular disease (HR, 1.93; 95% CI, 1.29-2.91). Only women with diabetes for more than 10 years had increased mortality from colorectal cancer (HR, 1.33; 95% CI, 1.01-1.76). CONCLUSIONS Among patients with colorectal cancer, preexisting diabetes was associated with increased risk of long-term mortality, particularly from other malignancies and cardiovascular disease. IMPACT Our findings highlight the importance of cardioprotection and cancer prevention to colorectal cancer survivors with diabetes.
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Affiliation(s)
- Chen Yuan
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Xuehong Zhang
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Ana Babic
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Vicente Morales-Oyarvide
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Yin Zhang
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Stephanie A Smith-Warner
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Brian M Wolpin
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Andrew T Chan
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Frank B Hu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Charles S Fuchs
- Yale Cancer Center, Smilow Cancer Hospital, New Haven, Connecticut
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
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16
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Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes 2020; 11:227-238. [PMID: 32547697 PMCID: PMC7284016 DOI: 10.4239/wjd.v11.i6.227] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 04/24/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
The incidence of diabetes and cancer has increased significantly in recent years. Furthermore, there are many common risk factors for both diabetes and cancer, such as obesity, sedentary lifestyle, smoking, and ageing. A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death. The incidence and mortality of various types of cancer, such as pancreas, liver, colorectal, breast, endometrial, and bladder cancers, have a modest growth in diabetics. However, diabetes may work as a protective factor for prostate cancer. Although the underlying biological mechanisms have not been totally understood, studies have validated that insulin/insulin-like growth factor (IGF) axis (including insulin resistance, hyperinsulinemia, and IGF), hyperglycemia, inflammatory cytokines, and sex hormones provide good circumstances for cancer cell proliferation and metastasis. Insulin/IGF axis activates several metabolic and mitogenic signaling pathways; hyperglycemia provides energy for cancer cell growth; inflammatory cytokines influence cancer cell apoptosis. Thus, these three factors affect all types of cancer, while sex hormones only play important roles in breast cancer, endometrial cancer, and prostate cancer. This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.
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Affiliation(s)
- Mina Wang
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yingying Yang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna 17177, Sweden
- Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna 17177, Sweden
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Diener C, Reyes-Escogido MDL, Jimenez-Ceja LM, Matus M, Gomez-Navarro CM, Chu ND, Zhong V, Tejero ME, Alm E, Resendis-Antonio O, Guardado-Mendoza R. Progressive Shifts in the Gut Microbiome Reflect Prediabetes and Diabetes Development in a Treatment-Naive Mexican Cohort. Front Endocrinol (Lausanne) 2020; 11:602326. [PMID: 33488518 PMCID: PMC7821428 DOI: 10.3389/fendo.2020.602326] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/20/2020] [Indexed: 12/26/2022] Open
Abstract
Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world's population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors were correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment-predominantly metformin-reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. In particular, we show that increased T2D risk is reflected in gradual changes in the gut microbiome. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen.
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Affiliation(s)
- Christian Diener
- Computational Genomics, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
- Gibbons Lab, Institute for Systems Biology, Seattle, WA, United States
| | | | - Lilia M. Jimenez-Ceja
- Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, Mexico
| | - Mariana Matus
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Claudia M. Gomez-Navarro
- Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, Mexico
| | - Nathaniel D. Chu
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Vivian Zhong
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - M. Elizabeth Tejero
- Computational Genomics, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
| | - Eric Alm
- Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Osbaldo Resendis-Antonio
- Computational Genomics, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico
- Human Systems Biology Laboratory, Coordinación de la Investigación Científica—Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
- *Correspondence: Osbaldo Resendis-Antonio, ; Rodolfo Guardado-Mendoza,
| | - Rodolfo Guardado-Mendoza
- Metabolic Research Laboratory, Department of Medicine and Nutrition, University of Guanajuato, León, Mexico
- Research Department, Hospital Regional de Alta Especialidad del Bajío, León, Mexico
- *Correspondence: Osbaldo Resendis-Antonio, ; Rodolfo Guardado-Mendoza,
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Tao H, O'Neil A, Choi Y, Wang W, Wang J, Wang Y, Jia Y, Chen X. Pre- and Post-diagnosis Diabetes as a Risk Factor for All-Cause and Cancer-Specific Mortality in Breast, Prostate, and Colorectal Cancer Survivors: a Prospective Cohort Study. Front Endocrinol (Lausanne) 2020; 11:60. [PMID: 32132977 PMCID: PMC7040305 DOI: 10.3389/fendo.2020.00060] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 01/30/2020] [Indexed: 02/05/2023] Open
Abstract
Objective: The relationship between diabetes and all- and cause-specific mortality in individuals with common cancers (breast, colorectal, and prostate) remains both under-researched and poorly understood. Methods: Cancer survivors (N = 37,993) from the National Health Interview Survey with linked data retrieved from the National Death Index served as our study participants. Cox proportional-hazards models were used to assess associations between pre- and post-diabetes and all-cause and cause-specific mortality. Results: Over a median follow-up period of 13 years, 2,350 all-cause, 698 cancer, and 506 CVD deaths occurred. Among all cancer survivors, patients with diabetes had greater risk of: all-cause mortality [hazard ratio (HR) 1.35, 95% CI = 1.27-1.43], cancer-specific mortality (HR: 1.14, 95% CI = 1.03-1.27), CVD mortality (HR: 1.36, 95% CI = 1.18-1.55), diabetes related mortality (HR: 17.18, 95% CI = 11.51-25.64), and kidney disease mortality (HR: 2.51, 95% CI = 1.65-3.82), compared with individuals without diabetes. The risk of all-cause mortality was also higher amongst those with diabetes and specific types of cancer: breast cancer (HR: 1.28, 95% CI = 1.12-1.48), prostate cancer (HR: 1.20, 95% CI = 1.03-1.39), and colorectal cancer (HR: 1.29, 95% CI = 1.10-1.50). Diabetes increased the risk of cancer-specific mortality among colorectal cancer survivors (HR: 1.36, 95% CI = 1.04-1.78) compared to those without diabetes. Diabetes was associated with higher risk of diabetes-related mortality when compared to non-diabetic breast (HR: 9.20, 95% CI = 3.60-23.53), prostate (HR: 18.36, 95% CI = 6.01-56.11), and colorectal cancer survivors (HR: 12.18, 95% CI = 4.17-35.58). Both pre- and post-diagnosis diabetes increased the risk of all-cause mortality among all cancer survivors. Cancer survivors with diabetes had similar risk of all-cause and CVD mortality during the second 5 years of diabetes and above 10 years of diabetes as compared to non-diabetic patients. Conclusions: Diabetes increased the risk of all-cause mortality among breast, prostate, and colorectal cancer survivors, not for pre- or post-diagnosis diabetes. Greater attention on diabetes management is warranted in cancer survivors with diabetes.
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Affiliation(s)
- Huan Tao
- Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China
| | - Adrienne O'Neil
- The Centre for Innovation in Mental and Physical Health and Clinical Treatment, Deakin University, Geelong, VIC, Australia
- Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC, Australia
| | - Yunseon Choi
- Department of Radiation Oncology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea
| | - Wei Wang
- School of Mathematical Sciences, Shanghai Jiao Tong University, Shanghai, China
| | - Junfeng Wang
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Yafeng Wang
- Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan University, Wuhan, China
- *Correspondence: Yafeng Wang
| | - Yongqian Jia
- Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China
- Yongqian Jia
| | - Xiong Chen
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Xiong Chen
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Xu H, Tan P, Zheng X, Ai J, Lin T, Jin X, Gong L, Lei H, Yang L, Wei Q. Metabolic syndrome and upper tract urothelial carcinoma: A retrospective analysis from a large Chinese cohort. Urol Oncol 2019; 37:291.e19-291.e28. [DOI: 10.1016/j.urolonc.2018.12.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 11/28/2018] [Accepted: 12/05/2018] [Indexed: 10/27/2022]
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Abdel-Rahman O. Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line chemotherapy among patients with metastatic colorectal cancer: a pooled analysis of two phase-III studies. Clin Transl Oncol 2018; 21:512-518. [PMID: 30182209 DOI: 10.1007/s12094-018-1939-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 08/27/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND The current analysis aims to provide an evaluation of the impact of diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX chemotherapy for patients with metastatic colorectal cancer (mCRC). METHODS This is a pooled analysis of the comparator arms of two clinical trials (NCT00272051; NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with mCRC. The overall survival and progression-free survival according to patient subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier analysis and log-rank testing. Propensity score matching was additionally conducted to account for heterogeneity in baseline characteristics of different subsets of patients. RESULTS A total of 756 patients were enrolled in the current analysis; of which 64 patients have pre-existing DM while 692 patients were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or progression-free survival difference was found among the two patient subsets (P = 0.501; P = 0.960, respectively). Moreover, metformin treatment does not affect overall or progression-free survival among diabetic patients (P = 0.598; P = 0.748, respectively). Repetition of overall and progression-free survival assessment following propensity score matching does not reveal any differences. Comparing diabetic to non-diabetic patients, there were no differences between the two groups in terms of acute oxaliplatin-induced neurological symptoms including cold-induced dysthesia (P = 0.600), laryngeal dysthesia (P = 0.707), jaw pain (P = 0.743) or muscle pain (P = 0.506). Moreover, no difference was seen between the two groups in terms of the incidence of long-term oxaliplatin-induced paresthesia (P = 0.107), highest grade of paresthesia (P = 0.498) or rates of recovery from paresthesia (P = 0.268). Diabetic patients have, however, a shorter time to develop oxaliplatin-induced paresthesia (P = 0.024). CONCLUSION DM does not seem to affect overall or progression-free survival of mCRC patients treated with first-line FOLFOX chemotherapy. Moreover, DM does not influence the incidence or severity of oxaliplatin-induced paresthesia in those patients while it might lead to a shorter time to develop oxaliplatin-induced paresthesia compared to non-diabetic patients.
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Affiliation(s)
- O Abdel-Rahman
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
- Department of Oncology, University of Calgary and Tom Baker Cancer Center, Calgary, AB, Canada.
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