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Bryan MS , Argos M , Andrulis IL , Hopper JL , Chang-Claude J , Malone K , John EM , Gammon MD , Daly M , Terry MB , Buys SS , Huo DZ , Olopade O , Genkinger JM , Jasmine F , Kibriya MG , Chen L , Ahsan H
Limited influence of germline genetic variation on all-cause mortality in women with early onset breast cancer: evidence from gene-based tests, single-marker regression, and whole-genome prediction
Breast Cancer Res Treat. 2017 Aug;164(3) :707-717
PMID: 28503721    PMCID: PMC5510603    URL: https://www.ncbi.nlm.nih.gov/pubmed/28503721
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Women diagnosed with breast cancer have heterogeneous survival outcomes that cannot be fully explained by known prognostic factors, and germline variation is a plausible but unconfirmed risk factor. We used three approaches to test the hypothesis that germline variation drives some differences in survival: mortality loci identification, tumor aggressiveness loci identification, and whole-genome prediction. The 2954 study participants were women diagnosed with breast cancer before age 50, with a median follow-up of 15 years who were genotyped on an exome array. We first searched for loci in gene regions that were associated with all-cause mortality. We next searched for loci in gene regions associated with five histopathological characteristics related to tumor aggressiveness. Last, we also predicted 10-year all-cause mortality on a subset of 1903 participants (3,245,343 variants after imputation) using whole-genome prediction methods. No risk loci for mortality or tumor aggressiveness were identified. This null result persisted when restricting to women with estrogen receptor-positive tumors, when examining suggestive loci in an independent study, and when restricting to previously published risk loci. Additionally, the whole-genome prediction model also found no evidence to support an association. Despite multiple complementary approaches, our study found no evidence that mortality in women with early onset breast cancer is influenced by germline variation. R25 CA057699/CA/NCI NIH HHS/ UM1 CA164920/CA/NCI NIH HHS/ U01 CA066572/CA/NCI NIH HHS/ U01 CA122171/CA/NCI NIH HHS/ RC1 CA145506/CA/NCI NIH HHS/ U19 CA148065/CA/NCI NIH HHS/ R01 CA094069/CA/NCI NIH HHS/ Netherlands Breast Cancer Res Treat. 2017 Aug;164(3):707-717. doi: 10.1007/s10549-017-4287-4. Epub 2017 May 13.
Bryan, Molly Scannell Argos, Maria Andrulis, Irene L. Hopper, John L. Chang-Claude, Jenny Malone, Kathleen John, Esther M. Gammon, Marilie D. Daly, Mary Terry, Mary Beth Buys, Saundra S. Huo, Dezheng Olopade, Olofunmilayo Genkinger, Jeanine M. Jasmine, Farzana Kibriya, Muhammad G. Chen, Lin Ahsan, Habibul 1573-7217