Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies

Gut. 2011 Dec;60(12):1703-11. doi: 10.1136/gut.2011.237727. Epub 2011 May 20.

Abstract

Background: Diabetes has been positively associated with the risk of colorectal cancer. This study investigated whether recently established risk variants for diabetes also have effects on colorectal cancer.

Methods: 19 single nucleotide repeats (SNPs) associated with type 2 diabetes in genome-wide association studies were tested in a case-control study of 2011 colorectal cancer cases and 6049 controls nested in the Multiethnic Cohort study as part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative. ORs and 95% CIs were estimated by unconditional logistic regression to evaluate the association between SNPs and colorectal cancer risk, adjusting for age, sex and race/ethnicity. Permutation testing was conducted to correct for multiple hypothesis testing.

Results: Four type 2 diabetes SNPs were associated with colorectal cancer risk: rs7578597 (THADA), rs864745 (JAZF1), rs5219 (KCNJ11) and rs7961581 (TSPAN8, LGR5). The strongest association was for the rs7578597 (THADA) Thr1187Ala missense polymorphism (P(trend)=0.004 adjusted for multiple testing), with the high risk allele for colorectal cancer being the low risk allele for diabetes. Similar patterns of associations were seen with further adjustment for diabetes status and body mass index. The association of diabetes status with colorectal cancer risk was somewhat weakened after adjustment for these SNPs.

Conclusion: The findings suggest that diabetes risk variants also influence colorectal cancer susceptibility, possibly through mechanisms different from those for diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Body Mass Index
  • Case-Control Studies
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / genetics*
  • Continental Population Groups / statistics & numerical data
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Ethnic Groups / statistics & numerical data
  • Female
  • Genome-Wide Association Study
  • Humans
  • Logistic Models
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors