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

TY - JOUR

T1 - Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

AU - Escala-Garcia, Maria

AU - Canisius, Sander

AU - Keeman, Renske

AU - Beesley, Jonathan

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Augustinsson, Annelie

AU - Becher, Heiko

AU - Beckmann, Matthias W

AU - Behrens, Sabine

AU - Bermisheva, Marina

AU - Bojesen, Stig E

AU - Bolla, Manjeet K

AU - Brenner, Hermann

AU - Canzian, Federico

AU - Castelao, Jose E

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J

AU - Couch, Fergus J

AU - Czene, Kamila

AU - Daly, Mary B

AU - Dennis, Joe

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Dunning, Alison M

AU - Easton, Douglas F

AU - Ekici, Arif B

AU - Eliassen, A Heather

AU - Fasching, Peter A

AU - Flyger, Henrik

AU - Gago-Dominguez, Manuela

AU - García-Closas, Montserrat

AU - García-Sáenz, José A

AU - Geisler, Jürgen

AU - Giles, Graham G

AU - Grip, Mervi

AU - Gündert, Melanie

AU - Hahnen, Eric

AU - Haiman, Christopher A

AU - Håkansson, Niclas

AU - Hall, Per

AU - Hamann, Ute

AU - Hartikainen, Jaana M

AU - Heemskerk-Gerritsen, Bernadette A M

AU - Hollestelle, Antoinette

AU - Hoppe, Reiner

AU - Hopper, John L

AU - Hunter, David J

AU - Jacot, William

AU - Jakubowska, Anna

AU - John, Esther M

AU - Jung, Audrey Y

AU - Kaaks, Rudolf

AU - Khusnutdinova, Elza

AU - Koppert, Linetta B

AU - Kraft, Peter

AU - Kristensen, Vessela N

AU - Kurian, Allison W

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Lindblom, Annika

AU - Luben, Robert N

AU - Lubiński, Jan

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Mavroudis, Dimitrios

AU - Muranen, Taru A

AU - Nevanlinna, Heli

AU - Olshan, Andrew F

AU - Olsson, Håkan

AU - Park-Simon, Tjoung-Won

AU - Patel, Alpa V

AU - Peterlongo, Paolo

AU - Pharoah, Paul D P

AU - Punie, Kevin

AU - Radice, Paolo

AU - Rennert, Gad

AU - Rennert, Hedy S

AU - Romero, Atocha

AU - Roylance, Rebecca

AU - Rüdiger, Thomas

AU - Ruebner, Matthias

AU - Saloustros, Emmanouil

AU - Sawyer, Elinor J

AU - Schmutzler, Rita K

AU - Schoemaker, Minouk J

AU - Scott, Christopher

AU - Southey, Melissa C

AU - Surowy, Harald

AU - Swerdlow, Anthony J

AU - Tamimi, Rulla M

AU - Teras, Lauren R

AU - Thomas, Emilie

AU - Tomlinson, Ian

AU - Troester, Melissa A

AU - Vachon, Celine M

AU - Wang, Qin

AU - Winqvist, Robert

AU - Wolk, Alicja

AU - Ziogas, Argyrios

AU - Michailidou, Kyriaki

AU - Chenevix-Trench, Georgia

AU - Bachelot, Thomas

AU - Schmidt, Marjanka K

AU - kConFab/AOCS Investigators

N1 - © 2021. The Author(s).

PY - 2021/10/5

Y1 - 2021/10/5

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-021-99409-3

DO - 10.1038/s41598-021-99409-3

M3 - SCORING: Journal article

C2 - 34611289

VL - 11

SP - 19787

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -