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Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk

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Abstract

We evaluated the association of a polymorphism in TCF7L2 (RS12255372) in the WNT signaling pathway, which previously has been strongly associated with risk of Type II Diabetes, with colorectal cancer (CRC) and adenoma in the prospective Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. Hyperinsulinemia may be related to the risk of colon adenoma and cancer, therefore this variant associated with reduced insulin secretion would be predicted to be inversely associated with colorectal cancer. Overall, in the NHS and HPFS, there was suggestive evidence for an inverse association associated with homozygosity for the minor allele of RS12255372 (TCF7L2 TT) and CRC (conditional and covariate adjusted OR = 0.63, 95% CI: 0.37–1.08; P for heterogeneity 0.52 for the association in women and men). In summary, the marginal association of the TCF7L2 SNP with CRC might be due to chance, but warrants further laboratory and epidemiological investigation.

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Abbreviations

CI:

Confidence interval

CRC:

Colorectal cancer

HPFS:

Health Professionals Follow-up Study

NHS:

Nurses’ Health Study

OR:

Odds Ratio

SNPs:

Single nucleotide polymorphisms

TCF7L2 :

T-cell factor 7 like 2

T2D:

Type II Diabetes

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Acknowledgments

We thank Pati Soule, Hardeep Ranu, and Craig Labadie for their laboratory assistance. We are indebted to the dedicated participants of the Nurses’ Health Study and the Health Professional Follow-up Study for their ongoing commitment. This research is supported by the National Institutes of Health Research Grants NIH: CA70817, CA87969, CA55075 and The Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA). A.H. is supported in part by training grant NIH T-32 CA 09001-30.

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Authors and Affiliations

  1. Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA

    Aditi Hazra & David J. Hunter

  2. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA

    Aditi Hazra, Charles S. Fuchs, Andrew T. Chan, Edward L. Giovannucci & David J. Hunter

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA

    Charles S. Fuchs

  4. Department of Nutrition, Harvard School of Public Health, Boston, MA, 02115, USA

    Edward L. Giovannucci & David J. Hunter

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  1. Aditi Hazra
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  2. Charles S. Fuchs
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Correspondence to Aditi Hazra.

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Hazra, A., Fuchs, C.S., Chan, A.T. et al. Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk. Cancer Causes Control 19, 975–980 (2008). https://doi.org/10.1007/s10552-008-9164-3

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  • DOI: https://doi.org/10.1007/s10552-008-9164-3

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