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Scannell Bryan M , Argos M , Andrulis IL , Hopper JL , Chang-Claude J , Malone K , John EM , Gammon MD , Daly M , Terry MB , Buys SS , Huo D , 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
AbstractPURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Despite multiple complementary approaches, our study found no evidence that mortality in women with early onset breast cancer is influenced by germline variation.
NotesScannell Bryan, Molly 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 eng Netherlands 2017/05/16 06:00 Breast Cancer Res Treat. 2017 Aug;164(3):707-717. doi: 10.1007/s10549-017-4287-4. Epub 2017 May 13.