Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

Author(s): Feng Y,  Rhie SK,  Huo D,  Ruiz-Narvaez EA,  Haddad SA,  Ambrosone CB,  John EM,  Bernstein L,  Zheng W,  Hu JJ,  Ziegler RG,  Nyante S,  Bandera EV,  Ingles SA,  Press MF,  Deming SL,  Rodriguez-Gil JL,  Zheng Y,  Yao S,  Han YJ,  Ogundiran TO,  Rebbeck TR,  Adebamowo C,  Ojengbede O,  Falusi AG,  Hennis A,  Nemesure B,  Ambs S,  Blot W,  Cai Q,  Signorello L,  Nathanson KL,  Lunetta KL,  Sucheston-Campbell LE,  Bensen JT,  Chanock SJ,  Marchand LL,  Olshan AF,  Kolonel LN,  Conti DV,  Coetzee GA,  Stram DO,  Olopade OI,  Palmer JR,  Haiman CA

Journal: Cancer Epidemiol Biomarkers Prev

Date: 2017 Jul

Major Program(s) or Research Group(s): CPFP

PubMed ID: 28377418

PMC ID: PMC5500414

Abstract: Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry.Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality.Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry.Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR.