Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans

Fang Chen, Gary K. Chen, Robert C. Millikan, Esther M. John, Christine B. Ambrosone, Leslie Bernstein, Wei Zheng, Jennifer Hu, Regina G. Ziegler, Sandra L. Deming, Elisa V. Bandera, Sarah Nyante, Julie R. Palmer, Timothy R. Rebbeck, Sue A. Ingles, Michael F. Press, Jorge L. Rodriguez-Gil, Stephen J. Chanock, Loïc Le Marchand, Laurence N. Kolonel & 3 others Brian E. Henderson, Daniel O. Stram, Christopher A. Haiman

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Abstract

Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and replicated associations (P < 0.05) with only 4 variants. Through fine-mapping, we identified markers in four regions that better capture the association with breast cancer risk in African Americans as defined by the index signal (2q35, 5q11, 10q26 and 19p13). We also identified statistically significant associations with markers in four separate regions (8q24, 10q22, 11q13 and 16q12) that are independent of the index signals and may represent putative novel risk variants. In aggregate, the more informative markers found in the study enhance the association of these risk regions with breast cancer in African Americans [per allele odds ratio (OR) = 1.18, P = 2.8 × 10 -24 versus OR = 1.04, P = 6.1 × 10 -5]. In this detailed analysis of the known breast cancer risk loci, we have validated and improved upon markers of risk that better characterize their association with breast cancer in women of African ancestry.

Original languageEnglish
Article numberddr367
Pages (from-to)4491-4503
Number of pages13
JournalHuman Molecular Genetics
Volume20
Issue number22
DOIs
StatePublished - Nov 1 2011

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Genetic Loci
African Americans
Breast Neoplasms
Genome-Wide Association Study
Odds Ratio
Alleles

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Chen, F., Chen, G. K., Millikan, R. C., John, E. M., Ambrosone, C. B., Bernstein, L., ... Haiman, C. A. (2011). Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. Human Molecular Genetics, 20(22), 4491-4503. [ddr367]. https://doi.org/10.1093/hmg/ddr367

Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. / Chen, Fang; Chen, Gary K.; Millikan, Robert C.; John, Esther M.; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer; Ziegler, Regina G.; Deming, Sandra L.; Bandera, Elisa V.; Nyante, Sarah; Palmer, Julie R.; Rebbeck, Timothy R.; Ingles, Sue A.; Press, Michael F.; Rodriguez-Gil, Jorge L.; Chanock, Stephen J.; Le Marchand, Loïc; Kolonel, Laurence N.; Henderson, Brian E.; Stram, Daniel O.; Haiman, Christopher A.

In: Human Molecular Genetics, Vol. 20, No. 22, ddr367, 01.11.2011, p. 4491-4503.

Research output: Contribution to journalArticle

Chen, F, Chen, GK, Millikan, RC, John, EM, Ambrosone, CB, Bernstein, L, Zheng, W, Hu, J, Ziegler, RG, Deming, SL, Bandera, EV, Nyante, S, Palmer, JR, Rebbeck, TR, Ingles, SA, Press, MF, Rodriguez-Gil, JL, Chanock, SJ, Le Marchand, L, Kolonel, LN, Henderson, BE, Stram, DO & Haiman, CA 2011, 'Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans', Human Molecular Genetics, vol. 20, no. 22, ddr367, pp. 4491-4503. https://doi.org/10.1093/hmg/ddr367
Chen F, Chen GK, Millikan RC, John EM, Ambrosone CB, Bernstein L et al. Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. Human Molecular Genetics. 2011 Nov 1;20(22):4491-4503. ddr367. https://doi.org/10.1093/hmg/ddr367
Chen, Fang ; Chen, Gary K. ; Millikan, Robert C. ; John, Esther M. ; Ambrosone, Christine B. ; Bernstein, Leslie ; Zheng, Wei ; Hu, Jennifer ; Ziegler, Regina G. ; Deming, Sandra L. ; Bandera, Elisa V. ; Nyante, Sarah ; Palmer, Julie R. ; Rebbeck, Timothy R. ; Ingles, Sue A. ; Press, Michael F. ; Rodriguez-Gil, Jorge L. ; Chanock, Stephen J. ; Le Marchand, Loïc ; Kolonel, Laurence N. ; Henderson, Brian E. ; Stram, Daniel O. ; Haiman, Christopher A. / Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 22. pp. 4491-4503.
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