Variation in TCF7L2 and increased risk of colon cancer

Aaron R. Folsom, James S. Pankow, James M. Peacock, Suzette J. Bielinski, Gerardo Heiss, Eric Boerwinkle

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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 JCF7L2 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 (̃ 17% here) of cases of colon cancer in the general population.

Original languageEnglish (US)
Pages (from-to)905-909
Number of pages5
JournalDiabetes care
Issue number5
StatePublished - May 2008

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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