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

Sonja I. Berndt, John D. Potter, Aditi Hazra, Meredith Yeager, Gilles Thomas, Karen W. Makar, Robert Welch, Amanda J. Cross, Wen Yi Huang, Robert E. Schoen, Edward Giovannucci, Andrew T. Chan, Stephen J. Chanock, Ulrike Peters, David J. Hunter, Richard B. Hayes

Research output: Contribution to journalArticle

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 × 10-6) than for single adenoma (ORper allele = 1.10, P = 0.03) with Pheterogeneity = 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.

Original languageEnglish (US)
Pages (from-to)2665-2672
Number of pages8
JournalHuman Molecular Genetics
Volume17
Issue number17
DOIs
StatePublished - 2008
Externally publishedYes

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Adenoma
Chromosomes
Alleles
Colorectal Neoplasms
Neoplasms
Odds Ratio
Confidence Intervals
Haplotypes
Prostatic Neoplasms
Logistic Models
Breast Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Berndt, S. I., Potter, J. D., Hazra, A., Yeager, M., Thomas, G., Makar, K. W., ... Hayes, R. B. (2008). Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. Human Molecular Genetics, 17(17), 2665-2672. https://doi.org/10.1093/hmg/ddn166

Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. / Berndt, Sonja I.; Potter, John D.; Hazra, Aditi; Yeager, Meredith; Thomas, Gilles; Makar, Karen W.; Welch, Robert; Cross, Amanda J.; Huang, Wen Yi; Schoen, Robert E.; Giovannucci, Edward; Chan, Andrew T.; Chanock, Stephen J.; Peters, Ulrike; Hunter, David J.; Hayes, Richard B.

In: Human Molecular Genetics, Vol. 17, No. 17, 2008, p. 2665-2672.

Research output: Contribution to journalArticle

Berndt, SI, Potter, JD, Hazra, A, Yeager, M, Thomas, G, Makar, KW, Welch, R, Cross, AJ, Huang, WY, Schoen, RE, Giovannucci, E, Chan, AT, Chanock, SJ, Peters, U, Hunter, DJ & Hayes, RB 2008, 'Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk', Human Molecular Genetics, vol. 17, no. 17, pp. 2665-2672. https://doi.org/10.1093/hmg/ddn166
Berndt, Sonja I. ; Potter, John D. ; Hazra, Aditi ; Yeager, Meredith ; Thomas, Gilles ; Makar, Karen W. ; Welch, Robert ; Cross, Amanda J. ; Huang, Wen Yi ; Schoen, Robert E. ; Giovannucci, Edward ; Chan, Andrew T. ; Chanock, Stephen J. ; Peters, Ulrike ; Hunter, David J. ; Hayes, Richard B. / Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 17. pp. 2665-2672.
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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 × 10-6) than for single adenoma (ORper allele = 1.10, P = 0.03) with Pheterogeneity = 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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AU - Cross, Amanda J.

AU - Huang, Wen Yi

AU - Schoen, Robert E.

AU - Giovannucci, Edward

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