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Diabetes Care. 2008 May;31(5):905-9. doi: 10.2337/dc07-2131. Epub 2008 Feb 11.

Variation in TCF7L2 and increased risk of colon cancer: the Atherosclerosis Risk in Communities (ARIC) Study.

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1
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Suite 300, 1300 S. Second St., Minneapolis, MN 55454-1015, USA. folsom@epi.umn.edu

Abstract

OBJECTIVE:

The purpose of this study was to determine whether a variation in the transcription factor 7-like 2 (TCF7L2) gene, which influences diabetes risk, is associated with incidence of cancers.

RESEARCH DESIGN AND METHODS:

We related diabetes and TCF7L2 variation with occurrence of several common cancers in a prospective cohort study of 13,117 middle-aged adults initially free of cancer in 1987-1989. We assessed five single nucleotide polymorphisms (SNPs) in TCF7L2 including the putative SNP (rs7903146) for diabetes. We identified incident cancers through 2000 via cancer registries, supplemented by hospital records.

RESULTS:

Diabetes was associated marginally inversely with incidence of prostate cancer but not with incidence of colorectal, colon, lung, or breast cancer. The T allele of rs7903146 (frequency 30%) was associated with increased risk of colorectal cancer and, more specifically, colon cancer, with adjusted hazard ratios (95% CI) of 1.0 for CC, 1.25 (0.85-1.83) for CT, and 2.15 (1.27-3.64) for TT genotypes (P(trend) = 0.009). TCF7L2 variation also was associated with lung cancer incidence in whites but not blacks, but residual confounding by smoking may be present.

CONCLUSIONS:

Subjects who were initially cancer-free and carrying certain genetic variants of TCF7L2, most notably the T allele of rs7903146, have an increased risk of colon cancer. This association appears to be an independent gene effect not explained by diabetes. Because the T allele of rs7903146 is common, if a causal link is established, this variant could account for a sizable proportion ( approximately 17% here) of cases of colon cancer in the general population.

PMID:
18268068
PMCID:
PMC2577771
DOI:
10.2337/dc07-2131
[Indexed for MEDLINE]
Free PMC Article
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