Genetic variations, reproductive aging, and breast cancer risk in African American and European American women: The Women's Circle of Health Study

• Published in: PloS one Vol. 12; no. 10; p. e0187205
• Main Authors: Coignet, Marie V, Zirpoli, Gary Robert, Roberts, Michelle R, Khoury, Thaer, Bandera, Elisa V, Zhu, Qianqian, Yao, Song
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26-10-2017; Public Library of Science (PLoS)
• Subjects: Adult; African Americans; African Americans - genetics; Aged; Aging; Aging (natural); Aging - genetics; Biology and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - physiopathology; Cancer; European Continental Ancestry Group - genetics; Female; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetic Variation; Genetics; Genome-wide association studies; Genomes; Health aspects; Health risk assessment; Health risks; Hormone replacement therapy; Humans; Life span; Medicine and Health Sciences; Menarche; Menopause; Middle Aged; Physiological aspects; Polymorphism, Single Nucleotide; Population studies; Populations; Reproduction - genetics; Risk analysis; Risk Factors; Single-nucleotide polymorphism; Studies; Womens health; Young Adult; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187205

Reproductive aging phenotypes, including age at menarche (AM) and age at natural menopause (ANM), are well-established risk factors for breast cancer. In recent years, many genetic variants have been identified in association with AM and ANM in genome-wide association studies among European populations. Using data from the Women's Circle of Health Study (WCHS) of 1,307 European-American (EA) and 1,365 African-American (AA) breast cancer cases and controls, we aimed to replicate 53 earlier GWAS variants for AM and ANM in AA and EA groups and to perform analyses on total and net reproductive lifespan (TRLS; NRLS). Breast cancer risk was also examined in relation to a polygenic risk score (PRS) for each of the reproductive aging phenotypes. We replicated a number of variants in EA women, including rs7759938 in LIN28B for AM and rs16991615 in MCM8 for ANM; whereas in the AA group, only one SNP (rs2947411 in TMEM18) for AM was directionally consistent and nominally significant. In analysis of TRLS and NRLS, several SNPs were significant, including rs466639 in RXRG that was associated with both phenotypes in both AA and EA groups. None of the PRS was associated with breast cancer risk. Given the paucity of data available among AA populations, our study contributes to the literature of genetics of reproductive aging in AA women and highlights the importance of cross population replication of GWAS variants.