Association of Diabetes Susceptibility Gene Calpain-10 with Pancreatic Cancer Among Smokers
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Association of Diabetes Susceptibility Gene Calpain-10 with Pancreatic Cancer Among Smokers Pui-yee Fong & Megan D. Fesinmeyer & Emily White & Federico M. Farin & Sengkeo Srinouanprachanh & Zahra Afsharinejad & Margaret T. Mandelson & Teresa A. Brentnall & Matt J. Barnett & Gary E. Goodman & Melissa A. Austin
Published online: 23 February 2010 # Springer Science+Business Media, LLC 2010
Abstract Objective The objective of this study was to test the association between calpain-10 (CAPN10), a diabetes susceptibility gene, with risk of pancreatic cancer (PC). Methods DNA samples from 83 incident exocrine PC cases and 166 controls, all of whom were smokers, were genotyped for four markers of CAPN10 in a nested case–control study based on the Beta-Carotene and Retinol Efficacy Trial (CARET), a randomized chemoprevention trial of subjects at high risk of lung cancer. Controls were matched on sex, P.-y. Fong : M. D. Fesinmeyer : M. A. Austin (*) Institute for Public Health Genetics, University of Washington, Box 357236, Seattle, WA 98195, USA e-mail: [email protected] E. White : M. A. Austin Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA M. D. Fesinmeyer : E. White : M. T. Mandelson : M. J. Barnett : G. E. Goodman : M. A. Austin Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA F. M. Farin : S. Srinouanprachanh : Z. Afsharinejad Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA T. A. Brentnall Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA M. T. Mandelson GH Center for Health Studies, Group Health Cooperative, Seattle, WA, USA
race, age, CARET intervention arm, duration of exposure to asbestos, and smoking history. Conditional logistic regression was used for statistical analyses. Results The minor allele of SNP-43 (rs3792267) in intron 3 was associated with increased risk of PC with an odds ratio of 1.57 (95%CI 1.03–2.38, p = 0.035) per allele. The three markers of the highest risk haplotype had an odds ratio of 1.98 (95%CI 1.12–3.49, p=0.019) for risk of PC compared to the most common haplotype. There was no evidence of interaction between either of these associations by diabetes status. Conclusion These results suggest that variation in CAPN10 may be associated with increased risk of PC among smokers. Thus, studies of genes associated with diabetes risk in PC are warranted in a larger population. Keywords pancreatic cancer . diabetes . calpain-10 . CAPN10
Introduction Pancreatic cancer (PC) is the fourth leading cause of cancer death in the USA [1]. It is estimated that PC will be diagnosed in over 37,000 people in 2008 resulting in over 34,000 deaths [1]. The majority of PC are exocrine tumors, and 95% of these are pancreatic ductal adenocarcinomas. Exocrine PC has a short survival time, with an average of only 4 months [2]. Smoking is the most established risk factor for PC with
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