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

TitleVariation in TCF7L2 and increased risk of colon cancer: the Atherosclerosis Risk in Communities (ARIC) Study.
Publication TypeJournal Article
Year of Publication2008
AuthorsFolsom AR, Pankow JS, Peacock JM, Bielinski SJ, Heiss G, Boerwinkle E
JournalDiabetes Care
Volume31
Issue5
Pagination905-9
Date Published2008 May
ISSN1935-5548
KeywordsAtherosclerosis, Blacks, Colonic Neoplasms, Female, Genetic Variation, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Registries, Risk Factors, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein, Whites
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.

DOI10.2337/dc07-2131
Alternate JournalDiabetes Care
PubMed ID18268068
PubMed Central IDPMC2577771
Grant ListN01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
R03-CA65473 / CA / NCI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States