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 journalArticle

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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 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
Volume31
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

T Cell Transcription Factor 1
Colonic Neoplasms
Neoplasms
Incidence
Single Nucleotide Polymorphism
Lung Neoplasms
Alleles
Genetic Transcription
Hospital Records
Gene Frequency
Genes
Registries
Colorectal Neoplasms
Prostatic Neoplasms
Cohort Studies
Research Design
Smoking
Genotype
Prospective Studies
Breast Neoplasms

ASJC Scopus subject areas

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

Cite this

Folsom, A. R., Pankow, J. S., Peacock, J. M., Bielinski, S. J., Heiss, G., & Boerwinkle, E. (2008). Variation in TCF7L2 and increased risk of colon cancer. Diabetes Care, 31(5), 905-909. https://doi.org/10.2337/dc07-2131

Variation in TCF7L2 and increased risk of colon cancer. / Folsom, Aaron R.; Pankow, James S.; Peacock, James M.; Bielinski, Suzette J; Heiss, Gerardo; Boerwinkle, Eric.

In: Diabetes Care, Vol. 31, No. 5, 05.2008, p. 905-909.

Research output: Contribution to journalArticle

Folsom, AR, Pankow, JS, Peacock, JM, Bielinski, SJ, Heiss, G & Boerwinkle, E 2008, 'Variation in TCF7L2 and increased risk of colon cancer', Diabetes Care, vol. 31, no. 5, pp. 905-909. https://doi.org/10.2337/dc07-2131
Folsom AR, Pankow JS, Peacock JM, Bielinski SJ, Heiss G, Boerwinkle E. Variation in TCF7L2 and increased risk of colon cancer. Diabetes Care. 2008 May;31(5):905-909. https://doi.org/10.2337/dc07-2131
Folsom, Aaron R. ; Pankow, James S. ; Peacock, James M. ; Bielinski, Suzette J ; Heiss, Gerardo ; Boerwinkle, Eric. / Variation in TCF7L2 and increased risk of colon cancer. In: Diabetes Care. 2008 ; Vol. 31, No. 5. pp. 905-909.
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