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Cho YK, Son Y, Saha A, Kim D, Choi C, Kim M, Park JH, Im H, Han J, Kim K, Jung YS, Yun J, Bae EJ, Seong JK, Lee MO, Lee S, Granneman JG, Lee YH. STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure. Nat Metab 2021; 3:428-441. [PMID: 33758424 DOI: 10.1038/s42255-021-00362-2] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 02/12/2021] [Indexed: 11/08/2022]
Abstract
Obesity reduces adipocyte mitochondrial function, and expanding adipocyte oxidative capacity is an emerging strategy to improve systemic metabolism. Here, we report that serine/threonine-protein kinase 3 (STK3) and STK4 are key physiological suppressors of mitochondrial capacity in brown, beige and white adipose tissues. Levels of STK3 and STK4, kinases in the Hippo signalling pathway, are greater in white than brown adipose tissues, and levels in brown adipose tissue are suppressed by cold exposure and greatly elevated by surgical denervation. Genetic inactivation of Stk3 and Stk4 increases mitochondrial mass and function, stabilizes uncoupling protein 1 in beige adipose tissue and confers resistance to metabolic dysfunction induced by high-fat diet feeding. Mechanistically, STK3 and STK4 increase adipocyte mitophagy in part by regulating the phosphorylation and dimerization status of the mitophagy receptor BNIP3. STK3 and STK4 expression levels are elevated in human obesity, and pharmacological inhibition improves metabolic profiles in a mouse model of obesity, suggesting STK3 and STK4 as potential targets for treating obesity-related diseases.
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Affiliation(s)
- Yoon Keun Cho
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Yeonho Son
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Abhirup Saha
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Doeun Kim
- BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
| | - Cheoljun Choi
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Minsu Kim
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Ji-Hyun Park
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Hyeonyeong Im
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Juhyeong Han
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Kyungmin Kim
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Young-Suk Jung
- College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Jeanho Yun
- Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan, Republic of Korea
| | - Eun Ju Bae
- College of Pharmacy, Chonbuk National University, Jeonju, Republic of Korea
| | - Je Kyung Seong
- Laboratory of Developmental Biology and Genomics, BK21 Plus Program for Advanced Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, and Korea Mouse Phenotyping Center, Seoul National University, Seoul, Republic of Korea
| | - Mi-Ock Lee
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Sangkyu Lee
- BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
| | - James G Granneman
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
- Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI, USA
| | - Yun-Hee Lee
- College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
- Bio-Max Institute, Seoul National University, Seoul, Republic of Korea.
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Kazemi B, Kalantari S, Pourshams A, Roudi R, Zali H, Bandehpour M, Kalantari A, Ghanbari R, D'Angelo A, Madjd Z. Identification of potential common molecular factors of pancreatic cancer and diabetes mellitus using microarray data analysis combined with bioinformatics techniques and experimental validation. BIOMEDICAL AND BIOTECHNOLOGY RESEARCH JOURNAL (BBRJ) 2021. [DOI: 10.4103/bbrj.bbrj_122_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Rosato V, Negri E, Bosetti C, Malats N, Gomez-Rubio P, Consortium P, Maisonneuve P, Miller AB, Bueno-de-Mesquita HB, Baghurst PA, Zatonski W, Petersen GM, Scelo G, Holcatova I, Fabianova E, Serraino D, Olson SH, Vioque J, Lagiou P, Duell EJ, Boffetta P, La Vecchia C. Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4). Eur J Cancer Prev 2020; 29:408-415. [PMID: 32740166 DOI: 10.1097/cej.0000000000000572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies. AIM To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy. METHODS We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models. RESULTS Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed <2 years before pancreatic cancer diagnosis and 1.11 (95% confidence interval, 0.96-1.29) when ≥2 years elapsed. The pooled odds ratio was 1.64 (95% confidence interval, 1.43-1.89) for patients who underwent cholecystectomy, as compared to those without cholecystectomy. The odds ratio was 7.00 (95% confidence interval, 4.13-11.86) for a surgery <2 years before pancreatic cancer diagnosis and 1.28 (95% confidence interval, 1.08-1.53) for a surgery ≥2 years before. CONCLUSIONS There appears to be no long-term effect of gallbladder disease on pancreatic cancer risk, and at most a modest one for cholecystectomy. The strong short-term association can be explained by diagnostic bias and reverse causation.
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Affiliation(s)
- Valentina Rosato
- Unit of Medical Statistics and Biometry, National Cancer Institute, IRCCS Foundation
| | - Eva Negri
- Department of Biomedical and Clinical Sciences, University of Milan
| | - Cristina Bosetti
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Núria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - Paulina Gomez-Rubio
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - PanGenEU Consortium
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Anthony B Miller
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - H Bas Bueno-de-Mesquita
- National Institute for Public Health and the Environment (RIVM), Bilthoven
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Peter A Baghurst
- Public Health, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - Witold Zatonski
- Health Promotion Foundation, Nadarzyn
- Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Gloria M Petersen
- Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester, New York, USA
| | - Ghislaine Scelo
- International Agency for Research on Cancer (IARC), Lyon, France
| | - Ivana Holcatova
- Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Eleonora Fabianova
- Regional Authority of Public Health, Banská Bystrica, Slovak Republic
- Faculty of Health, Catholic University, Ružomberok, Slovak Republic
| | - Diego Serraino
- Cancer Epidemiology Unit, National Cancer Institute Centro di Riferimento Oncologico, IRCCS, Aviano, Italy
| | - Sara H Olson
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jesús Vioque
- Institute for Health and Biomedical Research ISABIAL-UMH, Alicante
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Pagona Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
| | - Eric J Duell
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Paolo Boffetta
- The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Pizzato M, Turati F, Rosato V, La Vecchia C. Exploring the link between diabetes and pancreatic cancer. Expert Rev Anticancer Ther 2019; 19:681-687. [PMID: 31287962 DOI: 10.1080/14737140.2019.1642109] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear. Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time-risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer. Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes observed in several epidemiological studies indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumor. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle-age patients with new-onset diabetes may be considered.
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Affiliation(s)
- Margherita Pizzato
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano , Milan , Italy
| | - Federica Turati
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano , Milan , Italy
| | - Valentina Rosato
- Unit of Medical Statistics and Biometry, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , Milano , Italy
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano , Milan , Italy
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Primary and Secondary Prevention of Pancreatic Cancer. CURR EPIDEMIOL REP 2019. [DOI: 10.1007/s40471-019-00189-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Banfi G, Ardemagni A, Bravi S, Pacchioni M, Bonini P. Are Diabetic Metabolic Compensation and CA19.9 Really Correlated? Int J Biol Markers 2018; 11:207-10. [PMID: 9017444 DOI: 10.1177/172460089601100405] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Diabetes has been claimed to be a risk factor for pancreatic carcinoma, but it is probably a consequence of gland invasion from the neoplastic tissue. A link between diabetes and pancreatic carcinoma was suggested by means of biochemical markers of the diseases, namely glycated hemoglobin and CA19.9. Moreover, CA19.9 was proposed as a sensitive and useful marker of the severity of exocrine damage in diabetes, since the mucin decreased when metabolic compensation improved. We examined 64 diabetic patients (36 insulin dependent, 16 non insulin dependent, 12 treated with diet) by measuring CA19.9 using two different immunometric methods and glycemia and glycated hemoglobin. We observed that a correlation between CA19.9 and biochemical markers of metabolic compensation of diabetes was inexistent and no differences between insulin dependent and non insulin dependent patients were found. A high concentration of CA19.9 in a diabetic patient should be interpreted and evaluated in the same manner as for a non diabetic patient.
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Affiliation(s)
- G Banfi
- Servizio Intergrato di Medicina di Laboratorio, Istituto Scientifico H San Raffaele, Milano, Italy
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de Gaetano G, Costanzo S, Di Castelnuovo A, Badimon L, Bejko D, Alkerwi A, Chiva-Blanch G, Estruch R, La Vecchia C, Panico S, Pounis G, Sofi F, Stranges S, Trevisan M, Ursini F, Cerletti C, Donati MB, Iacoviello L. Effects of moderate beer consumption on health and disease: A consensus document. Nutr Metab Cardiovasc Dis 2016; 26:443-467. [PMID: 27118108 DOI: 10.1016/j.numecd.2016.03.007] [Citation(s) in RCA: 154] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 02/26/2016] [Accepted: 03/14/2016] [Indexed: 01/09/2023]
Abstract
A large evidence-based review on the effects of a moderate consumption of beer on human health has been conducted by an international panel of experts who reached a full consensus on the present document. Low-moderate (up to 1 drink per day in women, up to 2 in men), non-bingeing beer consumption, reduces the risk of cardiovascular disease. This effect is similar to that of wine, at comparable alcohol amounts. Epidemiological studies suggest that moderate consumption of either beer or wine may confer greater cardiovascular protection than spirits. Although specific data on beer are not conclusive, observational studies seem to indicate that low-moderate alcohol consumption is associated with a reduced risk of developing neurodegenerative disease. There is no evidence that beer drinking is different from other types of alcoholic beverages in respect to risk for some cancers. Evidence consistently suggests a J-shaped relationship between alcohol consumption (including beer) and all-cause mortality, with lower risk for moderate alcohol consumers than for abstainers or heavy drinkers. Unless they are at high risk for alcohol-related cancers or alcohol dependency, there is no reason to discourage healthy adults who are already regular light-moderate beer consumers from continuing. Consumption of beer, at any dosage, is not recommended for children, adolescents, pregnant women, individuals at risk to develop alcoholism, those with cardiomyopathy, cardiac arrhythmias, depression, liver and pancreatic diseases, or anyone engaged in actions that require concentration, skill or coordination. In conclusion, although heavy and excessive beer consumption exerts deleterious effects on the human body, with increased disease risks on many organs and is associated to significant social problems such as addiction, accidents, violence and crime, data reported in this document show evidence for no harm of moderate beer consumption for major chronic conditions and some benefit against cardiovascular disease.
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Affiliation(s)
- G de Gaetano
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy.
| | - S Costanzo
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy
| | - A Di Castelnuovo
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy
| | - L Badimon
- Cardiovascular Research Center (CSIC-ICCC), Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de Sant Pau, Barcelona, Spain
| | - D Bejko
- Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | - A Alkerwi
- Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | - G Chiva-Blanch
- Cardiovascular Research Center (CSIC-ICCC), Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de Sant Pau, Barcelona, Spain
| | - R Estruch
- Department of Internal Medicine, Hospital Clinic, University of Barcelona, Spain
| | - C La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Italy
| | - S Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - G Pounis
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy
| | - F Sofi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Don Carlo Gnocchi Foundation, ONLUS IRCCS, Florence, Italy
| | - S Stranges
- Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | | | - F Ursini
- Dipartimento di Medicina Molecolare, Università di Padova, Italy
| | - C Cerletti
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy
| | - M B Donati
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy
| | - L Iacoviello
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy
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Fan Y, Hu J, Feng B, Wang W, Yao G, Zhai J, Li X. Increased Risk of Pancreatic Cancer Related to Gallstones and Cholecystectomy: A Systematic Review and Meta-Analysis. Pancreas 2016; 45:503-9. [PMID: 26684857 DOI: 10.1097/mpa.0000000000000502] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR, 1.39; 95% CI, 1.28-1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR, 1.70; 95% CI, 1.30-2.21; P < 0.001; for cholecystectomy: RR, 1.31; 95% CI, 1.19-1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy alone is also an independent risk factor for pancreatic carcinogenesis.
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Affiliation(s)
- Yonggang Fan
- From the *Departments of General Surgery and †Anesthesiology, The First Affiliated Hospital of Henan Science and Technology University, Luoyang, Henan Province; and ‡Department of Physiology, The Basic Medicine College of Weifang Medical University, Weifang, Shandong Province, China
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Song S, Wang B, Zhang X, Hao L, Hu X, Li Z, Sun S. Long-Term Diabetes Mellitus Is Associated with an Increased Risk of Pancreatic Cancer: A Meta-Analysis. PLoS One 2015. [PMID: 26222906 PMCID: PMC4519136 DOI: 10.1371/journal.pone.0134321] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose Previous studies have shown a bidirectional relationship between diabetes and pancreatic cancer (PC). In particular, new-onset diabetes might be induced by PC, and people with long-term diabetes might be at increased risk for the development of PC. The purpose of our study was to examine whether long-term diabetes represented an independent risk factor for PC development. Methodology A literature search was performed by searching electronic databases for studies published before July 1, 2014, and relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. Data pertaining to diabetes were recorded at both individual and study levels, with RRs calculated separately to analyze the relationship between the duration of diabetes and the development of PC. Results Forty-four studies were included in this meta-analysis, including 18 studies with a case-control design, 5 with a nested case-control design and 21 with a cohort design. The overall summary estimate for the relationship between the population with a duration of diabetes ≥2 years and PC was 1.64 (1.52-1.78). The pooled RR (95% CI) of PC for the population with a duration of diabetes ≥5 years was 1.58 (1.42-1.75). For the population with a duration of diabetes ≥10 years, the RR (95% CI) of PC was 1.50 (1.28-1.75). Conclusions Our study suggests that long-term diabetes mellitus is associated with an increased risk of PC. However, the level of risk is negatively correlated with increasing diabetes mellitus duration.
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Affiliation(s)
- Shanshan Song
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Baosheng Wang
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xin Zhang
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Liliang Hao
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xianliang Hu
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhongxiang Li
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shaolong Sun
- Department of Pancreas and Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- * E-mail:
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Khawja SN, Mohammed S, Silberfein EJ, Musher BL, Fisher WE, Van Buren G. Pancreatic cancer disparities in African Americans. Pancreas 2015; 44:522-7. [PMID: 25872128 DOI: 10.1097/mpa.0000000000000323] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. The incidence of pancreatic cancer in African Americans is 50% to 90% higher than the incidence in other racial groups. African Americans also have the worst prognosis. This is an evidence-based review of pancreatic cancer in African Americans with particular emphasis on baseline characteristics, treatment, and survival. METHODS We queried PubMed in search for articles describing racial disparities in pancreatic cancer. Two categories of terms were "anded" together: pancreatic cancer terms and race terms. The last search was performed on November 14, 2013. RESULTS We summarized the data on pancreatic cancer baseline characteristics, treatment, and survival for African Americans that we obtained from the following databases: (1) Surveillance, Epidemiology, and End Results, 1988-2008; (2) California Cancer Registry 1988-1998; (3) Cancer Survivor Program of Orange County/San Diego Imperial Organization for Cancer Control, 1988-1998; and (4) Harris County, 1998-2010. CONCLUSIONS Overall, pancreatic cancer survival of African Americans has not significantly improved over the past several decades despite advances in multimodality therapy; African Americans continue to face worse outcomes than whites. Although baseline characteristics, treatment, and biological factors offer some explanation, they do not completely explain the disparities in incidence and survival.
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Affiliation(s)
- Shumaila N Khawja
- From the *Michael E. DeBakey Department of Surgery, †The Elkins Pancreas Center, ‡Dan L. Duncan Cancer Center, and §Department of Medicine, Baylor College of Medicine, Houston, TX
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Coats M, Shimi SM. Cholecystectomy and the risk of alimentary tract cancers: A systematic review. World J Gastroenterol 2015; 21:3679-3693. [PMID: 25834337 PMCID: PMC4375594 DOI: 10.3748/wjg.v21.i12.3679] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 12/05/2014] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between cholecystectomy and gastro-intestinal tract (GIT) cancers.
METHODS: We conducted a systematic review according to the PRISMA guidelines. A MEDLINE search was performed with predefined search criteria for English Language articles on the association between cholecystectomy and GIT cancers. Additional articles were retrieved by manual search of references. All relevant articles were accessed in full text. Data on study type; cases; controls; country; effect estimate; adjustments for confounders and quality of publication were extracted. The quality of the publications were scored by adherence to the STROBE checklist. The data for each part of the GIT were presented in separate tables.
RESULTS: Seventy-five studies and 5 meta-analyses satisfied the predefined criteria for inclusion and were included in this review. There were inconsistent reports and no strong evidence of an association between cholecystectomy and cancers of the oesophagus (Adenocarcinoma), pancreas, small bowel and right-sided colon cancers. In squamous cancer of the oesophagus, cancers of the stomach, liver, bile ducts, small bowel and left sided colon cancers, good quality studies suggested a lack of association with cholecystectomy. Equally, distal colon and rectal cancers were found not to be associated with cholecystectomy. Several mechanisms for carcinogenesis/promotion of carcinogensis have been proposed. These have focused on a role for bile salts in carcinogenesis with several potential mutagenic molecular events and gut metabolic hormones signaling cell proliferation or initiation of carcinogenesis.
CONCLUSION: This is a comprehensive review of the association between GIT cancers and cholecystectomy. This review found no clear association between cholecystectomy and GIT cancers.
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12
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Tang B, Lv J, Li Y, Yuan S, Wang Z, He S. Relationship between female hormonal and menstrual factors and pancreatic cancer: a meta-analysis of observational studies. Medicine (Baltimore) 2015; 94:e177. [PMID: 25700305 PMCID: PMC4554173 DOI: 10.1097/md.0000000000000177] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The objective of this study was to assess the relationship between female hormone and menstrual factors and pancreatic cancer (PC) through a meta-analysis of observational studies. We undertook a systematic literature search up to July 10, 2014 in PubMed and EMBASE databases. Combined relative risks (RRs) were estimated by random-effects models. Subgroup analysis was performed by study design, source of control, and geographic regions. Sensitivity analyses and publication bias were utilized to evaluate the robustness of our results. A total of 27 case-control and cohort studies were retrieved for this meta-analysis. No significant associations were observed between the risk of PC and age at menarche (RR = 0.94, 95% confidence interval [CI] 0.83-1.07), age at menopause (RR = 0.98, 95% CI 0.85-1.13), hysterectomy (RR = 0.97, 95% CI 0.84-1.11), oophorectomy (RR = 1.02, 95% CI 0.82-1.26), hormone replacement therapy (RR = 0.97, 95% CI 0.87-1.08), and oral contraceptives (RR = 1.09, 95% CI 0.96-1.23). This meta-analysis of observational studies does not support the hypothesis that exogenous hormone use and menstrual factors are associated with PC.
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Affiliation(s)
- Bo Tang
- From the Department of Hepatobiliary Surgery (BT, SY, ZW, SH), Affiliated Hospital of Guilin Medical University; Laboratory of Liver Injury and Repair Molecular Medicine (BT, SH), Guilin Medical University, Guilin; Department of Infectious Diseases (JL), People's Hospital of Beihai, Beihai; and Department of Medical Oncology (YL), Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, People's Republic of China
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13
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Cholelithiasis and risk of pancreatic cancer: systematic review and meta-analysis of 21 observational studies. Cancer Causes Control 2014; 25:1543-51. [DOI: 10.1007/s10552-014-0458-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2014] [Accepted: 08/06/2014] [Indexed: 12/31/2022]
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14
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Starup-Linde J, Karlstad O, Eriksen SA, Vestergaard P, Bronsveld HK, de Vries F, Andersen M, Auvinen A, Haukka J, Hjellvik V, Bazelier MT, Boer AD, Furu K, De Bruin ML. CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis. Curr Drug Saf 2014; 8:296-332. [PMID: 24215312 PMCID: PMC5421136 DOI: 10.2174/15748863113086660071] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 10/27/2013] [Accepted: 10/30/2013] [Indexed: 12/11/2022]
Abstract
Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Marie L De Bruin
- Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark.
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Investigating the synergistic interaction of diabetes, tobacco smoking, alcohol consumption, and hypercholesterolemia on the risk of pancreatic cancer: a case-control study in Italy. BIOMED RESEARCH INTERNATIONAL 2014; 2014:481019. [PMID: 24877100 PMCID: PMC4020558 DOI: 10.1155/2014/481019] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 04/23/2014] [Indexed: 02/08/2023]
Abstract
The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital “Agostino Gemelli” in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94–8.66; OR: 2.25, 95% CI: 1.30–3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods).
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16
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Nogueira L, Freedman ND, Engels EA, Warren JL, Castro F, Koshiol J. Gallstones, cholecystectomy, and risk of digestive system cancers. Am J Epidemiol 2014; 179:731-9. [PMID: 24470530 DOI: 10.1093/aje/kwt322] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged ≥66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract.
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Batabyal P, Vander Hoorn S, Christophi C, Nikfarjam M. Association of diabetes mellitus and pancreatic adenocarcinoma: a meta-analysis of 88 studies. Ann Surg Oncol 2014; 21:2453-62. [PMID: 24609291 DOI: 10.1245/s10434-014-3625-6] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced, incurable stage. Previous epidemiological data suggests that diabetes mellitus (DM) is a risk factor for PDAC, which may be important in early detection. However, the strength of this association needs to be determined, taking into account a number of recently published studies. METHODS A systematic review of the association between DM and PDAC was undertaken by searching electronic databases and journal references from 1973 to 2013. Summary estimates were obtained separately for case-control and cohort studies by means of a 'random effects' approach. Data pertaining to the DM was recorded and plotted at both an individual and study level, with the relative risks (RR) pooled separately to determine the relationship of DM duration and PDAC. RESULTS A total of 88 independent studies, including 50 cohort and 39 case-control studies were examined. The overall summary-combined RR was 1.97 (95 % CI 1.78-2.18) with marked heterogeneity that could not be clearly attributed to any subgroup analyses. The risk of PDAC was greatest early after the diagnosis of DM but remained elevated long after the diagnosis. The individual-level RR ranged from 6.69 at less than 1 year to 1.36 at 10 years. CONCLUSION The results demonstrate a strong association between PDAC and recently diagnosed DM, which may be attributed to a paraneoplastic effect. However, the presence of diabetes also remains a modest risk factor for the development of PDAC long-term. Selective screening of patients with new-onset DM for PDAC needs to be considered.
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Affiliation(s)
- Pikli Batabyal
- Department of Surgery, University of Melbourne, Austin Health, LTB 8, 145 Studley Rd, Heidelberg, Melbourne, VIC, 3084, Australia
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18
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Pezzilli R, Pagano N. Is diabetes mellitus a risk factor for pancreatic cancer? World J Gastroenterol 2013; 19:4861-4866. [PMID: 23946590 PMCID: PMC3740415 DOI: 10.3748/wjg.v19.i30.4861] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2013] [Revised: 04/21/2013] [Accepted: 05/08/2013] [Indexed: 02/06/2023] Open
Abstract
The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long period of time. The importance of this topic is due to two main causes: the possible use of recent onset diabetes as a marker of the disease and, in particular, as a specific marker of pancreatic cancer, and the selection of a population at risk for pancreatic cancer. Thus, we decided to make an in-depth study of this topic; thus, we carried out an extensive literature search in order to re-assess the current knowledge on this topic. Even if diabetes is found a decade before the appearance of pancreatic cancer as reported in meta-analytic studies, we cannot select those patients already having non detectable pancreatic cancer, at least with the imaging and biological techniques available today. We believe that more studies are necessary in order to definitively identify diabetes mellitus as a risk factor for pancreatic cancer taking into consideration that approximately 10 years are needed to diagnose symptomatic pancreatic cancer. At present, the answer to the as to whether diabetes and pancreatic cancer comes first similar to the adage of the chicken and the egg is that diabetes is the egg.
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Abstract
Up to 85% of patients with pancreatic cancer have diabetes or hyperglycaemia, which frequently manifests as early as 2-3 years before a diagnosis of pancreatic cancer. Conversely, patients with new-onset diabetes have a 5-8-fold increased risk of being diagnosed with pancreatic cancer within 1-3 years of developing diabetes. Emerging evidence now indicates that pancreatic cancer causes diabetes. As in type 2 diabetes, β-cell dysfunction and peripheral insulin resistance are seen in pancreatic cancer-induced diabetes. However, unlike in patients with type 2 diabetes, glucose control worsens in patients with pancreatic cancer in the face of ongoing, often profound, weight loss. Diabetes and weight loss, which precede cachexia onset by several months, are paraneoplastic phenomena induced by pancreatic cancer. Although the pathogenesis of these pancreatic cancer-induced metabolic alterations is only beginning to be understood, these are likely mechanisms to promote the survival and growth of pancreatic cancer in a hostile and highly desmoplastic microenvironment. Interestingly, these metabolic changes could enable early diagnosis of pancreatic cancer, if they can be distinguished from the ones that occur in patients with type 2 diabetes. One such possible biomarker is adrenomedullin, which is a potential mediator of β-cell dysfunction in pancreatic cancer-induced diabetes.
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20
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Morrison M. Pancreatic cancer and diabetes. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2013; 771:229-39. [PMID: 23393682 DOI: 10.1007/978-1-4614-5441-0_18] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Diabetes studies have increasingly been associated with several types of cancer. Diabetes and pancreatic cancer have a unique relationship. Genetic mutations, such as activation of the KRAS2 oncogene, inactivation of the tumor-suppressor gene CDKN2A, inactivation of the tumor-suppressor gene TP53 and deleted in pancreatic cancer 4 (DPC4) gene defects are seen in those with pancreatic cancer. Approximately 80% of those patients, diagnosed with pancreatic cancer, are identified as having concomitant diabetes with a poor prognostic factor. Damaged pancreatic tissue, secondary to pancreatic cancer, leads to diabetes as islet cells and beta cells are taken over by malignancy. Additionally, those on certain anti-diabetic regimens are shown to be at a higher risk of developing pancreatic cancer due to the effect of stimulation on the pancreatic beta and islet cells. Therefore, diabetes is thought to be both a potential cause and effect of pancreatic cancer. Diabetes has become a pandemic, and pancreatic cancer is one of the most lethal forms of malignancy known. In order to better understand these diseases and how they are associated, more research needs to be done. Particularly, research focusing on different types of diabetes in the setting of pancreatic cancer will be an important issue for further understanding of the link between diabetes and pancreatic cancer.
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Affiliation(s)
- Maureen Morrison
- Swedish Organ Transplant Division, Swedish Medical Center, Seattle, Washington, USA.
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21
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Lucenteforte E, La Vecchia C, Silverman D, Petersen GM, Bracci PM, Ji BT, Bosetti C, Li D, Gallinger S, Miller AB, Bueno-de-Mesquita HB, Talamini R, Polesel J, Ghadirian P, Baghurst PA, Zatonski W, Fontham E, Bamlet WR, Holly EA, Gao YT, Negri E, Hassan M, Cotterchio M, Su J, Maisonneuve P, Boffetta P, Duell EJ. Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol 2012; 23:374-82. [PMID: 21536662 PMCID: PMC3265544 DOI: 10.1093/annonc/mdr120] [Citation(s) in RCA: 153] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Revised: 02/25/2011] [Accepted: 02/28/2011] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.
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Affiliation(s)
- E. Lucenteforte
- Department of Epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri” Milan
- Department of Occupational Health, University of Milan, Milan, Italy
| | - C. La Vecchia
- Department of Epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri” Milan
- Department of Occupational Health, University of Milan, Milan, Italy
| | | | | | - P. M. Bracci
- University of California – San Francisco, San Francisco
| | - B. T. Ji
- National Cancer Institute, Bethesda
| | - C. Bosetti
- Department of Epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri” Milan
| | - D. Li
- MD Anderson Cancer Center, Houston, USA
| | | | - A. B. Miller
- Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
| | - H. B. Bueno-de-Mesquita
- National Institute for Public Health and the Environment (RIVM), Bilthoven
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - R. Talamini
- Centro di Riferimento Oncologico (CRO) – National Cancer Institute, Aviano (PN), Italy
| | - J. Polesel
- Centro di Riferimento Oncologico (CRO) – National Cancer Institute, Aviano (PN), Italy
| | - P. Ghadirian
- Epidemiology Research Unit, Research Center of the University of Montreal Hospital Centre (CRCHUM), Montreal, Canada
| | - P. A. Baghurst
- Public Health, Women's and Children's Hospital, Adelaide, Australia
| | - W. Zatonski
- Cancer Center & Institute of Oncology, Warsaw, Poland
| | - E. Fontham
- Louisiana State University, New Orleans, USA
| | | | - E. A. Holly
- University of California – San Francisco, San Francisco
| | - Y. T. Gao
- Shanghai Cancer Institute, Shanghai, China
| | - E. Negri
- Department of Epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri” Milan
| | - M. Hassan
- MD Anderson Cancer Center, Houston, USA
| | - M. Cotterchio
- Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
- Population Studies and Surveillance, Cancer Care Ontario, Toronto, Canada
| | - J. Su
- National Cancer Institute, Bethesda
| | | | - P. Boffetta
- International Prevention Research Institute, Lyon, France
- The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA
| | - E. J. Duell
- International Agency for Research on Cancer, Lyon, France
- Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
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22
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Olson SH. Selected medical conditions and risk of pancreatic cancer. Mol Carcinog 2012; 51:75-97. [PMID: 22162233 DOI: 10.1002/mc.20816] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
We review the current evidence for associations of several medical conditions with risk of pancreatic cancer, including allergies, pancreatitis, gall bladder disease, cholecystectomy, ulcers, gastrectomy, appendectomy, and tonsillectomy. There are consistent findings of reduced risk associated with presence of self-reported allergies, particularly hay fever but not asthma; data on other allergies are limited and inconclusive. Several studies provide evidence that patients with pancreatic cancer are more likely than comparison groups to report pancreatitis. Those studies that investigated the time between onset of pancreatitis and diagnosis of pancreatic cancer found that risk estimates declined with longer periods of time; however, increased risks were noted for long-term pancreatitis, indicating that this condition is both a risk factor and a sign of early disease. Increased risk was reported in association with cholelithiasis, but the few studies that considered time before diagnosis of cancer did not find increased risk for cholelithiasis diagnosed in the more distant past. There is weak evidence that cholecystectomy 2 or more years before cancer diagnosis is related to risk, but this is based on only a few studies. There is no consistent association between ulcers and risk, while gastrectomy may increase risk. Overall, study of these conditions, particularly those that are rare, presents methodologic challenges. Time between diagnoses is likely to be important but is not considered in most studies. Lack of adequate control in several studies for risk factors such as smoking and heavy alcohol use also makes it difficult to draw firm conclusions about these results.
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Affiliation(s)
- Sara H Olson
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA
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Abstract
Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5-fold to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and tumor growth. Use of the antidiabetic drug metformin has been associated with reduced risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. On the other hand, new-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early. Biomarkers that help define high-risk individuals for clinical screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes diabetes and how diabetes affects the clinical outcome of pancreatic cancer have yet to be fully determined. Improved understanding of the pathological mechanisms shared by diabetes and pancreatic cancer would be the key to the development of novel preventive and therapeutic strategies for this cancer.
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Affiliation(s)
- Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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Genkinger JM, Li R, Spiegelman D, Anderson KE, Albanes D, Bergkvist L, Bernstein L, Black A, van den Brandt PA, English DR, Freudenheim JL, Fuchs CS, Giles GG, Giovannucci E, Goldbohm RA, Horn-Ross PL, Jacobs EJ, Koushik A, Männistö S, Marshall JR, Miller AB, Patel AV, Robien K, Rohan TE, Schairer C, Stolzenberg-Solomon R, Wolk A, Ziegler RG, Smith-Warner SA. Coffee, tea, and sugar-sweetened carbonated soft drink intake and pancreatic cancer risk: a pooled analysis of 14 cohort studies. Cancer Epidemiol Biomarkers Prev 2011; 21:305-18. [PMID: 22194529 DOI: 10.1158/1055-9965.epi-11-0945-t] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. RESULTS No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing ≥900 to <0 g/d; 237g ≈ 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing ≥400 to 0 g/d; 237g ≈ 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing ≥250 to 0 g/d; 355g ≈ 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). CONCLUSION AND IMPACT Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.
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Affiliation(s)
- Jeanine M Genkinger
- Mailman School of Public Health, 722 w 168th St, Rm 803, New York, NY 10032, USA.
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Lin G, Zeng Z, Wang X, Wu Z, Wang J, Wang C, Sun Q, Chen Y, Quan H. Cholecystectomy and risk of pancreatic cancer: a meta-analysis of observational studies. Cancer Causes Control 2011; 23:59-67. [PMID: 22008981 DOI: 10.1007/s10552-011-9856-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2011] [Accepted: 10/08/2011] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Data from epidemiological studies related to the association of cholecystectomy and pancreatic cancer (PaC) risk are inconsistent. We conducted a meta-analysis of observational studies to explore this relationship. METHODS We identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 30 June 2011, and by searching the reference lists of pertinent articles. Summary relative risks with their 95% confidence intervals were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q statistic and the I (2). RESULTS A total of 18 studies (10 case-control studies, eight cohort studies) were included in this meta-analysis. Analysis of these 18 studies found that cholecystectomy was associated with a 23% excess risk of PaC (SRR = 1.23, 95% CI = 1.12-1.35), with moderate heterogeneity among these studies (p (heterogeneity) = 0.006, I (2) = 51.0%). Sub-grouped analyses revealed that the increased risk of PaC was independent of geographic location, gender, study design and confounders. There was no publication bias in the current meta-analysis. CONCLUSIONS The results of this meta-analysis suggest that individuals with a history of cholecystectomy may have an increased risk of pancreatic cancer.
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Affiliation(s)
- Genlai Lin
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
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Schiffman SC, Chu CK, Park J, Russell M, Keilin S, Kooby DA, Scoggins CR, McMasters KM, Martin RC. Is prior cholecystectomy associated with decreased survival in patients with resectable pancreatic adenocarcinoma following pancreaticoduodenectomy? Am J Surg 2011; 201:519-24. [DOI: 10.1016/j.amjsurg.2010.02.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2009] [Accepted: 02/04/2010] [Indexed: 01/23/2023]
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Abstract
OBJECTIVES Although half of all patients with pancreatic cancer are diabetic at the time of diagnosis, it remains unclear whether the diabetes associated with pancreatic cancer is a cause or an effect of the malignancy. METHODS Epidemiologic studies were reviewed, the geographic prevalence of diabetes and the incidence of pancreatic cancer were examined, and clinical and laboratory studies were reviewed. RESULTS Long-standing diabetes increases the risk of pancreatic cancer by 40% to 100%, and recent-onset diabetes is associated with a 4- to 7-fold increase in risk, such that 1% to 2% of patients with recent-onset diabetes will develop pancreatic cancer within 3 years. Treatment of diabetes or morbid obesity decreases the risk of pancreatic cancer, and metformin therapy decreases the risk due to both its antidiabetic and antineoplastic effects. Recent-onset diabetes associated with pancreatic cancer likely represents secondary or type 3 diabetes. The discrimination of type 3 diabetes from the more prevalent type 2 diabetes may identify the high-risk subgroup of diabetic patients in whom potentially curable pancreatic cancer may be found. CONCLUSIONS Type 2 and type 1 diabetes mellitus increase the risk of pancreatic cancer with a latency period of more than 5 years. Type 3 diabetes mellitus is an effect, and therefore a harbinger, of pancreatic cancer in at least 30% of patients.
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Yuan JM, Sun C, Butler LM. Tea and cancer prevention: epidemiological studies. Pharmacol Res 2011; 64:123-35. [PMID: 21419224 DOI: 10.1016/j.phrs.2011.03.002] [Citation(s) in RCA: 123] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Accepted: 03/02/2011] [Indexed: 12/23/2022]
Abstract
Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiological studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans.
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Affiliation(s)
- Jian-Min Yuan
- The Masonic Cancer Center, and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 425 East River Road, 554 MCRB, Minneapolis, MN 55455, USA.
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Abstract
OBJECTIVES Limited data are available to guide the management of very rare exocrine neoplasms of the pancreas (VREP). Available evidence suggests that VREP have different risk factors and prognoses from those of adenocarcinoma of the pancreas. The primary objectives for this study were to determine the survival, comorbidities, and response to treatment of patients seen at Mayo Clinic with VREP. METHODS We reviewed patients from 1975 to 2005 who had VREP and compared them to patients with adenocarcinomas that were matched for TNM, grade, and decade of treatment. RESULTS Sixty-six patients with VREP were identified. The most commonly identified neoplasms were acinar cell carcinoma (n = 15), small cell carcinoma (n = 12), and squamous cell carcinoma (n = 8). Abdominal discomfort and jaundice were the most common presenting symptoms. The median overall survival for patients with VREP, 10.4 months (range, 3.7-23 months), was better than that for matched controls, 8.2 months (range, 4-15.4 months) (P = 0.01). There was no difference in the survival of patients with stage 4 disease between cases, 8 months (range, 2.3-21.8 months), and controls, 6.7 months (range, 2.3-10.8 months) (P = 0.17). CONCLUSIONS We present one of the largest series of VREP to date. The overall survival of all patients with VREP was better than matched controls, but no statistical difference was seen between the groups with stage 4 disease.
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Gupta S, Wang F, Holly EA, Bracci PM. Risk of pancreatic cancer by alcohol dose, duration, and pattern of consumption, including binge drinking: a population-based study. Cancer Causes Control 2010; 21:1047-59. [PMID: 20349126 PMCID: PMC2883092 DOI: 10.1007/s10552-010-9533-6] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2009] [Accepted: 03/04/2010] [Indexed: 12/15/2022]
Abstract
Alcohol consumption is postulated to be a risk factor for pancreatic cancer (PCA), but clarification of degree of risk related to consumption characteristics is lacking. We examined the association between alcohol consumption and PCA in a population-based case-control study (532 cases, 1,701 controls) in the San Francisco Bay Area. Population-based controls were frequency-matched by sex, age within 5-year categories and county of residence to cases identified by the cancer registry's rapid case ascertainment. Detailed alcohol consumption data, including binge drinking (>or=5 drinks/day), were collected during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using adjusted unconditional logistic regression. Depending on dose, duration, and pattern of drinking, ORs were increased 1.5- to 6-fold among men but not women. In men, ORs increased with increasing overall alcohol consumption (22-35 drinks/week OR = 2.2, 95% CI = 1.1-4.0; >or=35 drinks/week OR = 2.6, 95% CI = 1.3-5.1, p-trend = 0.04). Most notable were effects with a history of binge drinking (OR = 3.5, 95% CI = 1.6-7.5) including increased number of drinks per day (p-trend = 0.002), and increased years of binge drinking (p-trend = 0.0006). In fully adjusted models that included smoking and other confounders, ORs for binge drinking in men were somewhat higher than in age-adjusted models. Results from our detailed analyses provide support for heavy alcohol consumption (including binge drinking) as a risk factor for PCA in men.
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Affiliation(s)
- Samir Gupta
- Division of Digestive and Liver Diseases, Harold C Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-8887, USA.
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Tramacere I, Scotti L, Jenab M, Bagnardi V, Bellocco R, Rota M, Corrao G, Bravi F, Boffetta P, La Vecchia C. Alcohol drinking and pancreatic cancer risk: a meta-analysis of the dose-risk relation. Int J Cancer 2010; 126:1474-86. [PMID: 19816941 DOI: 10.1002/ijc.24936] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In order to provide a more precise quantification of the association between alcohol consumption and pancreatic cancer risk, we performed a meta-analysis of relevant dose-risk results. We conducted a PubMed search of all case-control (N=21) and cohort (N=11) studies published up to March 2009. We computed summary relative risk (RR) estimates using either fixed- or, in the presence of heterogeneity, random-effects models. The pooled RR was 0.92 (95% confidence interval, 95% CI, 0.86-0.97) for <3 drinks/day and 1.22 (95% CI, 1.12-1.34) for > or = 3 drinks/day. The increased risk for heavy drinking was similar in women and men, but apparently stronger in cohort studies (RR=1.29), in studies with high quality index (RR=1.30), and did not appear to be explained by residual confounding by either history of pancreatitis or tobacco smoking. This meta-analysis provides strong evidence for the absence of a role of moderate drinking in pancreatic carcinogenesis, coupled to an increased risk for heavy alcohol drinking. Given the moderate increase in risk and the low prevalence of heavy drinkers in most populations, alcohol appears to be responsible only for a small fraction of all pancreatic cancers.
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Affiliation(s)
- Irene Tramacere
- Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milano, Italy.
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Matveyenko AV, Dry S, Cox HI, Moshtaghian A, Gurlo T, Galasso R, Butler AE, Butler PC. Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes 2009; 58:1604-15. [PMID: 19403868 PMCID: PMC2699878 DOI: 10.2337/db09-0058] [Citation(s) in RCA: 191] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE We sought to establish the extent and mechanisms by which sitagliptin and metformin singly and in combination modify islet disease progression in human islet amyloid polypeptide transgenic (HIP) rats, a model for type 2 diabetes. RESEARCH DESIGN AND METHODS HIP rats were treated with sitagliptin, metformin, sitagliptin plus metformin, or no drug as controls for 12 weeks. Fasting blood glucose, insulin sensitivity, and beta-cell mass, function, and turnover were measured in each group. RESULTS Sitagliptin plus metformin had synergistic effects to preserve beta-cell mass in HIP rats. Metformin more than sitagliptin inhibited beta-cell apoptosis. Metformin enhanced hepatic insulin sensitivity; sitagliptin enhanced extrahepatic insulin sensitivity with a synergistic effect in combination. beta-Cell function was partially preserved by sitagliptin plus metformin. However, sitagliptin treatment was associated with increased pancreatic ductal turnover, ductal metaplasia, and, in one rat, pancreatitis. CONCLUSIONS The combination of metformin and sitagliptin had synergistic actions to preserve beta-cell mass and function and enhance insulin sensitivity in the HIP rat model of type 2 diabetes. However, adverse actions of sitagliptin treatment on exocrine pancreas raise concerns that require further evaluation.
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Affiliation(s)
- Aleksey V Matveyenko
- Larry Hillblom Islet Research Center, Division of Endocrinology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
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Jiao L, Silverman DT, Schairer C, Thiébaut ACM, Hollenbeck AR, Leitzmann MF, Schatzkin A, Stolzenberg-Solomon RZ. Alcohol use and risk of pancreatic cancer: the NIH-AARP Diet and Health Study. Am J Epidemiol 2009; 169:1043-51. [PMID: 19299403 DOI: 10.1093/aje/kwp034] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The epidemiologic evidence for the role of alcohol use in pancreatic cancer development is equivocal. The authors prospectively examined the relation between alcohol use and risk of pancreatic cancer among 470,681 participants who were aged 50-71 years in 1995-1996 in the US National Institutes of Health-AARP Diet and Health Study. The authors identified 1,149 eligible exocrine pancreatic cancer cases through December 2003. Multivariate Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals with the referent group being light drinkers (<1 drink/day). The relative risks of developing pancreatic cancer were 1.45 (95% confidence interval (CI): 1.17, 1.80; P(trend) = 0.002) for heavy total alcohol use (>or=3 drinks/day, approximately 40 g of alcohol/day) and 1.62 (95% CI: 1.24, 2.10; P(trend) = 0.001) for heavy liquor use, compared with the respective referent group. The increased risk with heavy total alcohol use was seen in never smokers (relative risk = 1.35, 95% CI: 0.79, 2.30) and participants who quit smoking 10 or more years ago before baseline (relative risk = 1.41, 95% CI: 1.01, 2.00). These findings suggest a moderately increased pancreatic cancer risk with heavy alcohol use, particularly liquor; however, residual confounding by cigarette smoking cannot be completely excluded.
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Affiliation(s)
- Li Jiao
- Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.
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Genkinger JM, Spiegelman D, Anderson KE, Bergkvist L, Bernstein L, van den Brandt PA, English DR, Freudenheim JL, Fuchs CS, Giles GG, Giovannucci E, Hankinson SE, Horn-Ross PL, Leitzmann M, Männistö S, Marshall JR, McCullough ML, Miller AB, Reding DJ, Robien K, Rohan TE, Schatzkin A, Stevens VL, Stolzenberg-Solomon RZ, Verhage BAJ, Wolk A, Ziegler RG, Smith-Warner SA. Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol Biomarkers Prev 2009; 18:765-76. [PMID: 19258474 DOI: 10.1158/1055-9965.epi-08-0880] [Citation(s) in RCA: 123] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk. METHODS We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks and 95% confidence intervals were calculated using Cox proportional hazards models and then pooled using a random effects model. RESULTS A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate relative risk, 1.22; 95% confidence interval, 1.03-1.45 comparing >or=30 to 0 grams/day of alcohol; P value, test for between-studies heterogeneity=0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (P value, test for interaction=0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of >or=5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared with overweight and obese individuals (P value, test for interaction=0.01). DISCUSSION Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day.
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Affiliation(s)
- Jeanine M Genkinger
- Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA
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Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology 2008; 134:981-7. [PMID: 18395079 PMCID: PMC2323514 DOI: 10.1053/j.gastro.2008.01.039] [Citation(s) in RCA: 409] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2007] [Accepted: 01/10/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Information on the clinical profile of pancreatic cancer (PaC) associated diabetes (DM) is limited. We compared the prevalence and clinical characteristics of DM in subjects with and without PaC. METHODS We prospectively recruited 512 newly diagnosed PaC cases and 933 controls of similar age, who completed demographic and clinical questionnaires and had fasting blood glucose (FBG) levels measured at recruitment and after pancreaticoduodenectomy (n = 105). Subjects with a FBG level >126 mg/dL or who were on antidiabetic treatment were classified as having DM. RESULTS DM was more prevalent (47% vs 7%; P < .001) and predominantly of new onset (<2-year duration) (74% vs 53%; P = .002) among cases compared with controls. Among PaC cases, those with DM (n = 243) were older (68 +/- 10 vs 64 +/- 12 years; P < .001), reported higher usual adult body mass index (30 +/- 6 vs 27 +/- 5 kg/m(2); P < .001), and had a greater frequency of family history of DM (47% vs 31%; P < .001) compared with those without DM (n = 269). After pancreaticoduodenectomy, while DM resolved in 17 of 30 patients (57%) with new-onset DM, its prevalence was unchanged in patients with long-standing DM (n = 11) (P = .009). CONCLUSIONS PaC is a powerful diabetogenic state; DM associated with PaC is often new-onset, resolves following cancer resection, and appears to be associated with conventional risk factors for DM. New-onset DM in patients with PaC is likely induced by the tumor.
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Affiliation(s)
- Rahul Pannala
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN55905
| | - Jeffery B. Leirness
- Division of Biostatistics, Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN55905
| | - William R. Bamlet
- Division of Biostatistics, Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN55905
| | - Ananda Basu
- Division of Endocrinology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN55905
| | - Gloria M. Petersen
- Division of Biostatistics, Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN55905
| | - Suresh T. Chari
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN55905
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Abstract
Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.
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Iodice S, Gandini S, Maisonneuve P, Lowenfels AB. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch Surg 2008; 393:535-45. [DOI: 10.1007/s00423-007-0266-2] [Citation(s) in RCA: 374] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2007] [Accepted: 11/13/2007] [Indexed: 02/06/2023]
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Katsumichi I, Pour PM. Diabetes mellitus in pancreatic cancer: is it a causal relationship? Am J Surg 2008; 194:S71-5. [PMID: 17903450 DOI: 10.1016/j.amjsurg.2007.05.024] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2007] [Revised: 05/21/2007] [Accepted: 05/21/2007] [Indexed: 11/30/2022]
Abstract
The relationship between type 2 diabetes mellitus and pancreatic cancer (PC) is not clear. It has been reported that the increased release of islet amyloid polypeptides (IAPPs) is responsible for the impaired glucose tolerance in PC patients. However, no information exists on the patterns of IAPP expression in PC tissue in comparison with tissue from the normal pancreas and that of a patient with type 2 diabetes. Therefore, we performed a morphometric study and compared the patterns of IAPP expression in 5 normal pancreases (as a control), 6 pancreases from patients with type 2 diabetes, and 11 surgical PC specimens, which were processed for immunohistochemistry using anti-insulin and an anti-IAPP antibody. From the cancer tissue, sections were taken from the tumor (T) and from adjacent tumor-free areas (TF). The size of islets and the number of immunostained cells in these islets were recorded. In diabetes and PC, the size of islets and the number of beta-cells was significantly lower than in the controls. Also, the number of IAPP-expressing cells was significantly lower in diabetes and in the T area but not in the TF region. In addition, no characteristic changes found in diabetic pancreases were observed in the TF area, indicating that PC patients had no prior diabetic diseases. The reduction in the number of IAPP in the T area seems to argue against the role of IAPP in glucose abnormality in PC patients. The primary endocrine alteration in the tumor area suggests that cancer cells produce diabetogenic substances, the nature of which awaits further research.
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Affiliation(s)
- Iki Katsumichi
- UNMC Eppley Cancer Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA
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Chari ST, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M, Petersen GM. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008; 134:95-101. [PMID: 18061176 PMCID: PMC2271041 DOI: 10.1053/j.gastro.2007.10.040] [Citation(s) in RCA: 340] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2007] [Accepted: 10/11/2007] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The temporal association between diabetes mellitus and pancreatic cancer is poorly understood. We compared temporal patterns in diabetes prevalence in pancreatic cancer and controls. METHODS We reviewed the medical records of pancreatic cancer cases residing within 120 miles or less of Rochester, Minnesota, seen at the Mayo Clinic between January 15, 1981, and July 9, 2004, and approximately 2 matched controls/case residing locally. We abstracted all outpatient fasting blood glucose (FBG) levels for up to 60 months before index (ie, date of cancer diagnosis for cases) and grouped them into 12-month intervals; 736 cases and 1875 controls had 1 or more outpatient FBG levels in the medical record. Diabetes was defined as any FBG level of 126 mg/dL or greater or treatment for diabetes, and was defined as new onset when criteria for diabetes were first met 24 or fewer months before index, with at least 1 prior FBG level less than 126 mg/dL. RESULTS A higher proportion of pancreatic cancer cases compared with controls met the criteria for diabetes at any time in the 60 months before index (40.2% vs 19.2%, P < .0001). The proportions were similar in the -60 to -48 (P = .76) and -48 to -36 (P = .06) month time periods; however, a greater proportion of cases than controls met criteria for diabetes in the -36 to -24 (P = .04), -24 to -12 (P < .001), and -12 to 0 (P < .001) month time periods. Diabetes was more often new onset in cases vs controls (52.3% vs 23.6%, P < .0001). CONCLUSIONS Diabetes has a high (40%) prevalence in pancreatic cancer and frequently is new onset. Identification of a specific biomarker for pancreatic cancer-induced diabetes may allow screening for pancreatic cancer in new-onset diabetes.
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Affiliation(s)
- Suresh T. Chari
- Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Cynthia L. Leibson
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Kari G. Rabe
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Lawrence J. Timmons
- Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Jeanine Ransom
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Mariza de Andrade
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Gloria M. Petersen
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905
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Green tea and coffee intake and risk of pancreatic cancer in a large-scale, population-based cohort study in Japan (JPHC study). Eur J Cancer Prev 2007; 16:542-8. [DOI: 10.1097/cej.0b013e32809b4d30] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Ko AH, Wang F, Holly EA. Pancreatic cancer and medical history in a population-based case-control study in the San Francisco Bay Area, California. Cancer Causes Control 2007; 18:809-19. [PMID: 17632765 DOI: 10.1007/s10552-007-9024-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2006] [Accepted: 05/22/2007] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To determine the association between pancreatic cancer and medical conditions. METHODS A large population-based case-control study identified pancreatic cancer cases in the San Francisco Bay Area between 1995 and 1999. A total of 1,701 controls were randomly selected from the same population and were frequency-matched to 532 cases by sex and age. In-person interviews were conducted with no proxy interviews. RESULTS Prior history of gallbladder disease was associated with increased risk of pancreatic cancer (OR = 1.6, 95% CI = 1.2-2.2), with the highest risk occurring for gallbladder disease not caused by cholelithiasis (OR = 2.1, 95% CI = 1.1-3.7). Risk was associated with cholelithiasis only for participants diagnosed within the year before their pancreatic cancer (OR = 15, 95% CI = 6.2-34), and for those with cholelithiasis and cholecystectomy within the same time frame (OR = 28, 95% CI = 8.2-96). Gastric and/or duodenal ulcers were associated with increased risk of pancreatic cancer for individuals with ulcers of <or=two years duration (OR = 2.3, 95% CI = 1.1-4.6). Hyperthyroidism (OR = 2.1, 95% CI = 1.0-4.2) and "other" thyroid conditions (OR = 2.2, 95% CI = 1.1-4.2) were associated with increased risk. Participants with at least one first-degree relative with pancreatic cancer had an increased risk (OR = 1.6, 95% CI = 1.1-2.5). CONCLUSION History of recent gallbladder conditions, gastric and/or duodenal ulcers may represent an early manifestation of pancreatic cancer rather than an independent risk factor. These results warrant further investigation in pooled analyses.
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Affiliation(s)
- Andrew H Ko
- Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA, USA
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Wang F, Gupta S, Holly EA. Diabetes mellitus and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California. Cancer Epidemiol Biomarkers Prev 2006; 15:1458-63. [PMID: 16896032 DOI: 10.1158/1055-9965.epi-06-0188] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Diabetes has been postulated to be both a risk factor and a consequence of pancreatic cancer, but the degree of risk and associated clinical factors remain unclear. METHODS We conducted a population-based case-control study of pancreatic cancer in the San Francisco Bay Area between 1995 and 1999. Rapid case ascertainment through the Surveillance, Epidemiology and End Results registry for cases and random selection from the general population for controls were employed to identify study participants with no proxy interviews. RESULTS Five hundred thirty-two cases and 1,701 controls were interviewed. Participants with pancreatic cancer were more likely to report a history of diabetes (13%) than were controls [9%; odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.1-2.1]. Compared with diabetics in the control group, diabetics in the case group had a shorter duration of diabetes (P = 0.0003) and a larger proportion of insulin users (P = 0.002). Risk for pancreatic cancer varied with duration of diabetes (OR, 2.4; 95% CI, 1.4-4.0 for 1-4 years; OR, 2.0; 95% CI, 1.2-3.4 for 5-9 years; and OR, 0.86; 95% CI, 0.52-1.4 for >or=10 years diabetes duration; P(trend) = 0.004). Among diabetics, use of oral diabetes medication or insulin for >or=5 years was not associated with pancreatic cancer, but insulin use of <5 years was associated with a 6.8-fold risk for pancreatic cancer (95% CI, 3.7-12). CONCLUSION Recent-onset diabetes may be a complication or an early marker of pancreatic cancer. Diabetes of short duration with insulin use conferred a substantially elevated risk for pancreatic cancer and may reflect insulin resistance that is elicited by pancreatic cancer.
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Affiliation(s)
- Furong Wang
- Department of Epidemiology and Biostatistics, University of California San Francisco, Suite 280, 3333 California Street, San Francisco, CA 94118-1944, USA
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Gupta S, Vittinghoff E, Bertenthal D, Corley D, Shen H, Walter LC, McQuaid K. New-onset diabetes and pancreatic cancer. Clin Gastroenterol Hepatol 2006; 4:1366-72; quiz 1301. [PMID: 16945591 DOI: 10.1016/j.cgh.2006.06.024] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Although many individuals with pancreatic cancer have diabetes, the association between new-onset diabetes mellitus and the subsequent incidence of pancreatic cancer is unclear. METHODS We conducted a retrospective cohort study to estimate the incidence of pancreatic cancer subsequent to a new diabetes diagnosis and to evaluate factors associated with a subsequent pancreatic cancer diagnosis. We used the Veterans Health Administration National Patient Care Database to assemble a cohort of 1,421,794 US veterans without prior diabetes or pancreatic cancer diagnoses. We recorded coding for new diabetes diagnoses (> or =2 International Classification of Diseases-9 codes for diabetes within a 12-month period), pancreatic cancer, age, sex, race, and common gastrointestinal symptoms. RESULTS A total of 36,631 (2.6%) of the 1,421,794 veterans were diagnosed with new-onset diabetes in 1999; 149 subsequently received a diagnosis of pancreatic cancer. Pancreatic cancer incidence in patients with new-onset diabetes (83.8/100,000 person-years) was 2.2-fold higher (95% confidence interval, 1.84-2.56) than in nondiabetics, and was highest during the first 2 years after diabetes diagnosis. One additional pancreatic cancer was diagnosed for every 332 new diabetics over 6 years. A subsequent pancreatic cancer diagnosis (among new-onset diabetics) was associated independently with younger age groups, changes in bowel habits, constipation, epigastric pain, and malnutrition. CONCLUSIONS New-onset diabetes was associated with a significantly increased rate of pancreatic cancer diagnosis, particularly in the first 2 years after diabetes diagnosis. Factors associated with pancreatic cancer diagnosis included younger age groups and the presence of gastrointestinal symptoms. The absolute incidence of pancreatic cancer was low.
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Affiliation(s)
- Samir Gupta
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
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Yun JE, Jo I, Park J, Kim MT, Ryu HG, Odongua N, Kim E, Jee SH. Cigarette smoking, elevated fasting serum glucose, and risk of pancreatic cancer in Korean men. Int J Cancer 2006; 119:208-12. [PMID: 16450398 DOI: 10.1002/ijc.21816] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Pancreatic cancer is one of the most fatal human cancers and continues to be a major unsolved health problem. The goal of this study was to estimate the independent effects and interactions between cigarette smoking and diabetes on the risk of pancreatic cancer in Korean male population. Cigarette smoking and the risk of incidence and death from pancreatic cancer were examined in a 10-year prospective cohort study of 446,407 Korean men aged 40 to 65 years who received health insurance from the National Health Insurance Corporation and who had a medical evaluation in 1992. Relative risks (RR) and 95% confidence intervals (CI) were calculated using a Cox proportional hazards model after adjusting for age, body mass index, exercise and alcohol use. Current smoking was associated with an increased risk of incidence (RR = 1.7, 95% CI = 1.6-1.9) and mortality (RR = 1.6, 95% CI = 1.4-1.7) from pancreatic cancer. The RR for pancreatic cancer increased with both duration and amount of smoking. Diabetes was also associated with an increased risk of both incidence (RR = 1.8, 95% CI = 1.5-2.2) and mortality (RR = 1.7, 95% CI = 1.4-2.1) from pancreatic cancer. There was no interaction between smoking and fasting serum glucose in terms of pancreatic cancer risk. Thus, our prospective study has demonstrated that cigarette smoking and elevated fasting serum glucose are independently associated with an increased risk of pancreatic cancer in a large cohort of Korean males.
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Affiliation(s)
- Ji Eun Yun
- Department of Public Health, Graduate School, Yonsei University, Seoul, Korea
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46
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Shen M, Boffetta P, Olsen JH, Andersen A, Hemminki K, Pukkala E, Tracey E, Brewster DH, McBride ML, Pompe-Kirn V, Kliewer EV, Tonita JM, Chia KS, Martos C, Jonasson JG, Colin D, Scélo G, Brennan P. A pooled analysis of second primary pancreatic cancer. Am J Epidemiol 2006; 163:502-11. [PMID: 16421239 DOI: 10.1093/aje/kwj073] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor.
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Affiliation(s)
- Min Shen
- International Agency for Research on Cancer, Lyon, France.
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47
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Hruban RH, Canto MI, Griffin C, Kern SE, Klein AP, Laheru D, Yeo CJ. Treatment of familial pancreatic cancer and its precursors. ACTA ACUST UNITED AC 2006; 8:365-75. [PMID: 16162302 DOI: 10.1007/s11938-005-0039-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Approximately 10% of pancreatic cancers are believed to have a familial basis. The familial aggregation of pancreatic cancers provides a unique opportunity to prevent the development of pancreatic cancer, to identify and treat precancerous lesions of the pancreas, and to advance our understanding of the genetic basis for the development of all forms of pancreatic cancer. After appropriate genetic counseling, individuals with a strong family history of pancreatic cancer can now be tested for inherited genetic alterations that are known to increase the risk of pancreatic cancer. These include germline BRCA2, STK11/LKB1, p16/CDKN2A and PRSS1 gene mutations. Individuals with one of these inherited genetic alterations and individuals with a strong family history of pancreatic cancer can be counseled on smoking cessation and possible dietary modifications. Selected individuals, even if they are asymptomatic, can be screened using a combination of endoscopic ultrasound and multidetector computed tomography. Patients found to have a mass lesion in the pancreas would then be candidates for surgical resection. The resection of noninvasive precancers will cure these lesions before they have the opportunity to spread and metastasize. Even with the best early detection efforts, some patients will still be diagnosed with an invasive cancer. Surgical resection of invasive pancreatic cancer is proven to be safe and can provide long-term survival in patients with small, node-negative, and margin-negative cancers. Chemotherapy and radiation therapy are effective in some patients with invasive pancreatic cancer, but these therapies do not usually result in long-term cures. Individuals with a family history of pancreatic cancer may also choose to join a research study such as the National Familial Pancreas Tumor Registry.
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Affiliation(s)
- Ralph H Hruban
- The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, 401 North Broadway, Weinberg 2249, Baltimore, MD 21231, USA.
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48
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Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology 2005. [PMID: 16083707 DOI: 10.1053/j.gastro.2005.05.007] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. METHODS We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age > or =50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. RESULTS Of 2122 diabetic subjects, 18 (0.85%) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56%) were diagnosed <6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70-12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61-12.74) years but did not differ significantly with respect to BMI values (29.2 +/- 6.8 vs 26.5 +/- 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69%, respectively), but this did not reach statistical significance. CONCLUSIONS Approximately 1% of diabetes subjects aged > or =50 years will be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation.
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Affiliation(s)
- Suresh T Chari
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rochester, Minnesota 55905, USA.
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Huxley R, Ansary-Moghaddam A, Berrington de González A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005; 92:2076-83. [PMID: 15886696 PMCID: PMC2361795 DOI: 10.1038/sj.bjc.6602619] [Citation(s) in RCA: 773] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer is the eighth major form of cancer-related death worldwide, causing 227 000 deaths annually. Type-II diabetes is widely considered to be associated with pancreatic cancer, but whether this represents a causal or consequential association is unclear. We conducted a meta-analysis to examine this association. A computer-based literature search from 1966 to 2005 yielded 17 case–control and 19 cohort or nested case–control studies with information on 9220 individuals with pancreatic cancer. The age and sex-adjusted odds ratio (OR) for pancreatic cancer associated with type-II diabetes was obtained from each study. The combined summary odds ratio was 1.82 (95% confidence interval (95% CI) 1.66–1.89), with evidence of heterogeneity across the studies (P=0.002 for case–control and P=0.05 for cohort studies) that was explained, in part, by higher risks being reported by smaller studies and studies that reported before 2000. Individuals in whom diabetes had only recently been diagnosed (<4 years) had a 50% greater risk of the malignancy compared with individuals who had diabetes for ⩾5 years (OR 2.1 vs 1.5; P=0.005). These results support a modest causal association between type-II diabetes and pancreatic cancer.
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Affiliation(s)
- R Huxley
- The George Institute for International Health, The University of Sydney, PO Box M201, Missenden Road, Sydney NSW 2050, Australia.
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Damiano J, Bordier L, Le Berre JP, Margery J, Dupuy O, Mayaudon H, Bauduceau B. Should pancreas imaging be recommanded in patients over 50 years when diabetes is discovered because of acute symptoms? DIABETES & METABOLISM 2004; 30:203-7. [PMID: 15223996 DOI: 10.1016/s1262-3636(07)70111-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The relationship between diabetes mellitus and cancer of the pancreas is complex and incompletely understood. Nevertheless, it is generally agreed that new-onset diabetes in a patient over 50 Years old is a classical indication of pancreatic cancer. But there is no official directive in France that a scan should routinely be performed in such cases. We have studied 115 patients aged over 50 who were hospitalized for new-onset diabetes (fewer than 30 days) whose instability required insulin treatment. Routine imaging revealed abdominal disorders in 14 patients, 6 (5.2%) of whom were suffering from pancreatic adenocarcinomas. No clinical indication or laboratory test, apart from an unusually severe anorexia, suggested the discovered disorders. We therefore routinely carry out a pancreas scan, preferably by MRI, on all patients over 50 Years old presenting with new-onset diabetes, even if there are not clinical or laboratory indications of cancer. This is the only way in which small pancreatic cancers can be detected, thus providing the best hopes for successful treatment. Unfortunately, too often, this approach also detects only tumors that are already well developed. However, nowadays, it is not conceivable for a clinical team to discharge a patient from hospital with such a serious disease undiagnosed.
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Affiliation(s)
- J Damiano
- Service d'Endocrinologie, Hôpital d'Instruction des Armées Bégin, 94160 Saint-Mandé, France
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