Dataset Information

A comprehensive examination of breast cancer risk loci in African American women.

ABSTRACT: Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive disease. We also observed suggestive associations with variants (at P < 5 × 10(-6)) in three separate regions (6q25, 14q13, 22q12) that may represent novel risk variants. Directional consistency of association observed for ?65-70% of currently known genetic variants for breast cancer in women of African ancestry implies a shared functional common variant at most loci. To validate and enhance the spectrum of alleles that define associations at the known breast cancer risk loci, as well as genome-wide, will require even larger collaborative efforts in women of African ancestry.

SUBMITTER: Feng Y

PROVIDER: S-EPMC4168823 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A comprehensive examination of breast cancer risk loci in African American women.

Feng Ye Y Stram Daniel O DO Rhie Suhn Kyong SK Millikan Robert C RC Ambrosone Christine B CB John Esther M EM Bernstein Leslie L Zheng Wei W Olshan Andrew F AF Hu Jennifer J JJ Ziegler Regina G RG Nyante Sarah S Bandera Elisa V EV Ingles Sue A SA Press Michael F MF Deming Sandra L SL Rodriguez-Gil Jorge L JL Palmer Julie R JR Olopade Olufunmilayo I OI Huo Dezheng D Adebamowo Clement A CA Ogundiran Temidayo T Chen Gary K GK Stram Alex A Park Karen K Rand Kristin A KA Chanock Stephen J SJ Le Marchand Loic L Kolonel Laurence N LN Conti David V DV Easton Douglas D Henderson Brian E BE Haiman Christopher A CA

Human molecular genetics 20140522 20

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. ...[more]

PMID: 24852375

Similar Datasets

Project description:African Americans have a disproportionate burden of aggressive young-onset breast cancer. Genomic testing for inherited predisposition to breast cancer is increasingly common in clinical practice, but comprehensive mutation profiles remain unknown for most minority populations. We evaluated 289 patients who self-identified as African American with primary invasive breast cancer and with personal or family cancer history or tumor characteristics associated with high genetic risk for all classes of germline mutations in known breast cancer susceptibility genes using a validated targeted capture and multiplex sequencing approach. Sixty-eight damaging germline mutations were identified in 65 (22 %, 95 % CI 18-28 %) of the 289 subjects. Proportions of patients with unequivocally damaging mutations in a breast cancer gene were 26 % (47/180; 95 % confident interval [CI] 20-33 %) of those with breast cancer diagnosis before age 45; 25 % (26/103; 95 % CI 17-35 %) of those with triple-negative breast cancer (TNBC); 29 % (45/156; 95 % CI 22-37 %) of those with a first or second degree relative with breast cancer before age 60 or with ovarian cancer; and 57 % (4/7; 95 % CI 18-90 %) of those with both breast and ovarian cancer. Of patients with mutations, 80 % (52/65) carried mutations in BRCA1 and BRCA2 genes and 20 % (13/65) carried mutations in PALB2, CHEK2, BARD1, ATM, PTEN, or TP53. The mutational allelic spectrum was highly heterogeneous, with 57 different mutations in 65 patients. Of patients meeting selection criteria other than family history (i.e., with young age at diagnosis or TNBC), 48 % (64/133) had very limited information about the history of cancer in previous generations of their families. Mutations in BRCA1 and BRCA2 or another breast cancer gene occur in one in four African American breast cancer patients with early onset disease, family history of breast or ovarian cancer, or TNBC. Each of these criteria defines patients who would benefit from genomic testing and novel therapies targeting DNA repair pathways.

Dataset Information

A comprehensive examination of breast cancer risk loci in African American women.

Publications

A comprehensive examination of breast cancer risk loci in African American women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets