Association of Diabetes Susceptibility Gene Calpain-10 with Pancreatic Cancer Among Smokers
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The objective of this study was to test the association between calpain-10 (CAPN10), a diabetes susceptibility gene, with risk of pancreatic cancer (PC).
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, race, age, CARET intervention arm, duration of exposure to asbestos, and smoking history. Conditional logistic regression was used for statistical analyses.
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.
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.
Keywordspancreatic cancer diabetes calpain-10 CAPN10
This work was supported by NIH grants R21 CA115878-01, R25 CA115878-01, U01-CA063673, and P30ES07033. Specimens were from CARET Serum Bank maintained at Fred Hutchinson Cancer Research Center (FHCRC).