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Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.

Published version
Peer-reviewed

Type

Article

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Authors

Escala-Garcia, Maria 
Canisius, Sander 
Keeman, Renske 
Beesley, Jonathan 
Anton-Culver, Hoda 

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10-8 and 4.42 × 10-8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Description

Keywords

Biomarkers, Tumor, Breast Neoplasms, Cancer Survivors, Female, Genetic Predisposition to Disease, Genetic Variation, Germ Cells, Germ-Line Mutation, Humans, Kaplan-Meier Estimate, Polymorphism, Single Nucleotide

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
National Cancer Institute (U19CA148537)
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
European Commission (16563)
European Commission (223175)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (10710)
Cancer Research UK (12014)
Cancer Research UK (10118)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)
Cancer Research UK (16563)
Cancer Research Uk (None)