Limited influence of germline genetic variation on all-cause mortality in women with early onset breast cancer
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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. / Scannell Bryan, Molly; Argos, Maria; Andrulis, Irene L; Hopper, John L; Chang-Claude, Jenny; Malone, Kathleen E; John, Esther M; Gammon, Marilie D; Daly, Mary B; Terry, Mary-Beth; Buys, Saundra; Huo, Dezheng; Olopade, Olofunmilayo; Genkinger, Jeanine M; Jasmine, Farzana; Kibriya, Muhammad G; Chen, Lin; Ahsan, Habibul.
in: BREAST CANCER RES TR, Jahrgang 164, Nr. 3, 08.2017, S. 707-717.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Limited influence of germline genetic variation on all-cause mortality in women with early onset breast cancer
T2 - evidence from gene-based tests, single-marker regression, and whole-genome prediction
AU - Scannell Bryan, Molly
AU - Argos, Maria
AU - Andrulis, Irene L
AU - Hopper, John L
AU - Chang-Claude, Jenny
AU - Malone, Kathleen E
AU - John, Esther M
AU - Gammon, Marilie D
AU - Daly, Mary B
AU - Terry, Mary-Beth
AU - Buys, Saundra
AU - Huo, Dezheng
AU - Olopade, Olofunmilayo
AU - Genkinger, Jeanine M
AU - Jasmine, Farzana
AU - Kibriya, Muhammad G
AU - Chen, Lin
AU - Ahsan, Habibul
PY - 2017/8
Y1 - 2017/8
N2 - PURPOSE: 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.
AB - PURPOSE: 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.
KW - Journal Article
U2 - 10.1007/s10549-017-4287-4
DO - 10.1007/s10549-017-4287-4
M3 - SCORING: Journal article
C2 - 28503721
VL - 164
SP - 707
EP - 717
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 3
ER -