Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.
Escala-Garcia M., Canisius S., Keeman R., Beesley J., Anton-Culver H., Arndt V., Augustinsson A., Becher H., Beckmann MW., Behrens S., Bermisheva M., Bojesen SE., Bolla MK., Brenner H., Canzian F., Castelao JE., Chang-Claude J., Chanock SJ., Couch FJ., Czene K., Daly MB., Dennis J., Devilee P., Dörk T., Dunning AM., Easton DF., Ekici AB., Eliassen AH., Fasching PA., Flyger H., Gago-Dominguez M., García-Closas M., García-Sáenz JA., Geisler J., Giles GG., Grip M., Gündert M., Hahnen E., Haiman CA., Håkansson N., Hall P., Hamann U., Hartikainen JM., Heemskerk-Gerritsen BAM., Hollestelle A., Hoppe R., Hopper JL., Hunter DJ., Jacot W., Jakubowska A., John EM., Jung AY., Kaaks R., Khusnutdinova E., Koppert LB., Kraft P., Kristensen VN., Kurian AW., Lambrechts D., Le Marchand L., Lindblom A., Luben RN., Lubiński J., Mannermaa A., Manoochehri M., Margolin S., Mavroudis D., Muranen TA., Nevanlinna H., Olshan AF., Olsson H., Park-Simon T-W., Patel AV., Peterlongo P., Pharoah PDP., Punie K., Radice P., Rennert G., Rennert HS., Romero A., Roylance R., Rüdiger T., Ruebner M., Saloustros E., Sawyer EJ., Schmutzler RK., Schoemaker MJ., Scott C., Southey MC., Surowy H., Swerdlow AJ., Tamimi RM., Teras LR., Thomas E., Tomlinson I., Troester MA., Vachon CM., Wang Q., Winqvist R., Wolk A., Ziogas A., kConFab/AOCS Investigators None., Michailidou K., Chenevix-Trench G., Bachelot T., Schmidt MK.
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.