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

Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96817, USA.
Gut (Impact Factor: 14.66). 05/2011; 60(12):1703-11. DOI: 10.1136/gut.2011.237727
Source: PubMed


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

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    • "These discrepancies could be due to differences in size and composition of the investigated populations. Recently, the type 2 diabetes SNP rs7961581 (TSPAN8/LGR5) was found to be associated with colorectal cancer risk [18], but there was no evidence for this association in our database. Surprisingly, we registered a lower variant allele frequency assigned to SNP rs10879303 in colorectal cancer patients compared to healthy individuals, which could be a possible hint at a protective function of this SNP against colorectal cancer. "
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