Association of diabetes susceptibility gene calpain-10 with pancreatic cancer among smokers

Our plain-English summary of Association of diabetes susceptibility gene calpain-10 with pancreatic cancer among smokers, by P.Y. Fong, M.D. Fesinmeyer, E. White, et al (Journal of Gastrointestinal Cancer, 2010).

The study

• Authors: P.Y. Fong, M.D. Fesinmeyer, E. White, F.M. Farin, S. Srinouanprachanh, Z. Afsharinejad, M.T. Mandelson, T.A. Brentnall, M.J. Barnett, G.E. Goodman, M.A. Austin
• Journal: Journal of Gastrointestinal Cancer
• Published: 2010;41(3):203-8
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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, 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.

In plain English

This study asked whether variants in calpain-10 (CAPN10), a diabetes-linked gene, were associated with pancreatic cancer in smokers. It did not test whether asbestos causes pancreatic cancer; asbestos exposure was a matching factor, and 16 cases and 32 controls came from the trial's asbestos-exposed group. The authors ran a nested case-control study within the Beta-Carotene and Retinol Efficacy Trial (CARET), which enrolled heavy smokers and asbestos-exposed workers. They compared 83 people with exocrine pancreatic cancer and 166 matched cancer-free controls, all current or former smokers. Each extra copy of the "A" variant of one marker, SNP-43, went with higher odds of pancreatic cancer (odds ratio 1.57, 95% CI 1.03 to 2.38), but this was not significant after correction for multiple testing. Compared with the most common three-marker combination (TG-ins), CG-ins had an odds ratio of 1.98 (95% CI 1.12 to 3.49) and TA-ins 1.78 (95% CI 1.15 to 2.80). The other three markers showed no significant association, and results did not appear to differ by diabetes status. The authors called this a pilot study with low power and said larger studies are warranted.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nested case-control study (described by the authors as a pilot study) within a randomized chemoprevention trial
• Who was studied: 83 people with confirmed incident exocrine pancreatic cancer and 166 cancer-free matched controls (2 per case), all current or former smokers. All were participants in CARET, a trial of heavy smokers or asbestos-exposed workers at high risk of lung cancer, with cases available as of September 1, 2004. Cases diagnosed with lung cancer were excluded. The asbestos-exposed CARET group included 16 cases (19.3%) and 32 controls (19.3%). Overall, 75% were male, 94% were white, and the mean baseline age was about 61 years.
• Exposure: Inherited variation at four markers of the CAPN10 gene: SNP-44, SNP-43, Indel-19 and SNP-63, plus three-marker haplotypes. Asbestos exposure was not the exposure studied; controls were matched to cases on asbestos exposure, along with age, sex, race, CARET intervention arm and smoking history.
• Main results:
  • Among the 83 cases and 166 controls, each additional copy of the minor allele "A" of SNP-43 was associated with increased risk of pancreatic cancer (OR=1.57, 95%CI 1.03 to 2.38, p=0.035).
  • The SNP-43 result was not statistically significant after Bonferroni correction for multiple comparisons.
  • No significant association was found for the other three markers. Per the table: SNP-44 OR 1.69 (95% CI 0.99 to 2.91, p=0.055); Indel-19 OR 1.31 (0.86 to 1.99); SNP-63 OR 1.00 (0.53 to 1.90).
  • Compared with the most common haplotype (TG-ins), haplotype CG-ins had OR 1.98 (95% CI 1.12 to 3.49, p=0.019) and haplotype TA-ins had OR 1.78 (95% CI 1.15 to 2.80, p=0.010), per Table 2.
  • There was no evidence that the associations differed by self-reported diabetes status.
  • At baseline, 16% of cases (13 of 83) and 13% of controls (21 of 166) self-reported diabetes.
• The authors' conclusion: The authors concluded that the intronic SNP-43 and its haplotype in CAPN10 were associated with pancreatic cancer among smokers in the CARET cohort. They said variation in CAPN10 may be associated with increased risk and that larger studies of diabetes-related genes are warranted.
• Limitations the authors state:
  • The high-risk sample of smokers may not represent the general population.
  • The small sample size gave low power to detect associations, including interaction with diabetes.
  • Diabetes status was self-reported.
  • Only four markers were used, possibly not capturing all important variation in the CAPN10 gene.

Topics

Medical terms in this study, explained in our Lexicon: nested case-control study, Lung Cancer, Odds Ratio.

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