Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Coignet MV

PROVIDER: S-EPMC5658184 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Coignet Marie V MV Zirpoli Gary Robert GR Roberts Michelle R MR Khoury Thaer T Bandera Elisa V EV Zhu Qianqian Q Yao Song S

PloS one 20171026 10

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 v ...[more]

PMID: 29073238

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Project description:African American (AA) women are more likely than European American (EA) women to be diagnosed with early, aggressive breast cancer. Possible differences in innate immune pathways (e.g., inflammatory responses) have received little attention as potential mechanisms underlying this disparity. We evaluated distributions of selected genetic variants in innate immune pathways in AA and EA women, and examined their associations with breast cancer risk within the Women's Circle of Health Study (WCHS). In stage I of the study (864 AA and 650 EA women) we found that genotype frequencies for 35 of 42 tested SNPs (18 candidate genes) differed between AAs and EAs (corroborated by ancestry informative markers). Among premenopausal AA women, comparing variant allele carriers to non-carriers, reduced breast cancer risk was associated with CXCL5-rs425535 (OR=0.61, P=0.02), while among EA women, there were associations with TNFA-rs1799724 (OR =2.31, P =0.002) and CRP-rs1205 (OR=0.54, P=0.01). For postmenopausal women, IL1B-rs1143627 (OR=1.80, P=0.02) and IL1B-rs16944 (OR=1.85, P =0.02) were associated with risk among EA women, with significant associations for TNFA-rs1799724 limited to estrogen receptor (ER) positive cancers (OR=2.0, P =0.001). However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P0.0012 (0.05/42) except for TNFA-rs1799724 in ER positive cancers. In a stage II validation (1,365 AA and 1,307 EA women), we extended evaluations for four SNPs (CCL2-rs4586, CRP-rs1205, CXCL5-rs425535, and IL1RN-rs4251961), which yielded similar results. In summary, distributions of variants in genes involved in innate immune pathways were found to differ between AA and EA populations, and showed differential associations with breast cancer according to menopausal or ER status. These results suggest that immune adaptations suited to ancestral environments may differentially influence breast cancer risk among EA and AA women.

Project description:BackgroundPrior research shows between-race differences in women's knowledge and emotions related to having dense breasts, thus suggesting that between-race differences in behavioral decision-making following receipt of breast density (BD) notifications are likely. Guided by the theory of planned behavior, this study examined differences in emotion-related responses (i.e., anxiety, worry, confusion) and behavioral cognition (e.g., intentions, behavioral attitudes) following receipt of BD notifications among African American (AA) and European American (EA) women. This study also examined whether race-related perceptions (i.e., discrimination, group-based medical mistrust), relevant knowledge and socioeconomic status (SES) explained the between race differences.MethodMichigan women (N = 457) who presented for routine screening mammogram and had dense breasts, no prior breast cancer diagnoses, and had screen-negative mammograms were recruited from July, 2015 to March 2016. MANOVA was used to examine between race differences in psychological responses (i.e., emotional responses and behavioral cognition), and a multi-group structural regression model was used to examine whether race-related constructs, knowledge and SES mediated the effect of race on emotional responses and behavioral cognition. Prior awareness of BD was accounted for in all analyses.ResultsAA women generally reported more negative psychological responses to receiving BD notifications regardless of prior BD awareness. AA women had more favorable perceptions related to talking to their physicians about the BD notifications. Generally, race-related perceptions, SES, and related knowledge partially accounted for the effect of race on psychological response. Race-related perceptions and SES partially accounted for the differences in behavioral intentions. Between-race differences in emotional responses to BD notifications did not explain differences in women's intentions to discuss BD notifications with their physicians.ConclusionsFuture examinations are warranted to examine whether there are between-race differences in actual post-BD notification behaviors and whether similar race-related variables account for differences.

Dataset Information

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

Publications

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

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