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Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk

  1. Author:
    Berndt, S. I.
    Potter, J. D.
    Hazra, A.
    Yeager, M.
    Thomas, G.
    Makar, K. W.
    Welch, R.
    Cross, A. J.
    Huang, W. Y.
    Schoen, R. E.
    Giovannucci, E.
    Chan, A. T.
    Chanock, S. J.
    Peters, U.
    Hunter, D. J.
    Hayes, R. B.

  2. Author Address

    Berndt, Sonja I.; Yeager, Meredith, Thomas, Gilles, Welch, Robert, Cross, Amanda J.; Huang, Wen-Yi, Chanock, Stephen J.; Hayes, Richard B.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Potter, John D.; Makar, Karen W.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Potter, John D.; Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hazra, Aditi, Giovannucci, Edward, Hunter, David J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Yeager, Meredith, Welch, Robert] SAIC Frederick Inc, Adv Technol Program, Natl Canc Inst Frederick, Frederick, MD 21702 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Schoen, Robert E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Giovannucci, Edward, Hunter, David J.] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward, Chan, Andrew T.; Hunter, David J.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
    1. Year: 2008
  2. Journal: Human Molecular Genetics
    1. 17
    2. 17
    3. Pages: 2665-2672
  4. Type of Article: Article
  1. Abstract:

    Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (ORper allele = 1.16, 95% CI: 1.07-1.25, P = 0.0002) and cancer (ORper allele = 1.17, 95% CI: 1.01-1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (ORper allele = 1.29, P = 5.6 x 10(-6)) than for single adenoma (ORper allele = 1.10, P = 0.03) with P-heterogeneity = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas.

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External Sources

  1. PMID: 18535017

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