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

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, M. W., Behrens, S., Bermisheva, M., Bojesen, S. E., Bolla, M. K., Brenner, H., Canzian, F., Castelao, J. E., Chang-Claude, J., Chanock, S. J., Couch, F. J., Czene, K., Daly, M. B., Dennis, J., Devilee, P., Dörk, T., Dunning, A. M., Easton, D. F., Ekici, A. B., Eliassen, A. H., Fasching, P. A., Flyger, H., Gago-Dominguez, M., García-Closas, M., García-Sáenz, J. A., Geisler, J., Giles, G. G., Grip, M., Gündert, M., Hahnen, E., Haiman, C. A., Håkansson, N., Hall, P., Hamann, U., Hartikainen, J. M., Heemskerk-Gerritsen, B. A. M., Hollestelle, A., Hoppe, R., Hopper, J. L., Hunter, D. J., Jacot, W., Jakubowska, A., John, E. M., Jung, A. Y., Kaaks, R., Khusnutdinova, E., Koppert, L. B., Kraft, P., Kristensen, V. N., Kurian, A. W., Lambrechts, D., Le Marchand, L., Lindblom, A., Luben, R. N., Lubiński, J., Mannermaa, A., Manoochehri, M., Margolin, S., Mavroudis, D., Muranen, T. A., Nevanlinna, H., Olshan, A. F., Olsson, H., Park-Simon, T., Patel, A. V., Peterlongo, P., Pharoah, P. D. P., Punie, K., Radice, P., Rennert, G., Rennert, H. S., Romero, A., Roylance, R., Rüdiger, T., Ruebner, M., Saloustros, E., Sawyer, E. J., Schmutzler, R. K., Schoemaker, M. J., Scott, C., Southey, M. C., Surowy, H., Swerdlow, A. J., Tamimi, R. M., Teras, L. R., Thomas, E., Tomlinson, I., Troester, M. A., Vachon, C. M., Wang, Q., Winqvist, R., Wolk, A., Ziogas, A., kConFab/AOCS Investigators, Michailidou, K., Chenevix-Trench, G., Bachelot, T., & Schmidt, M. K. Scientific Reports, 11(1):19787, October, 2021.
doi abstract bibtex

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.

@article{escala-garcia_germline_2021,
title = {Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis},
volume = {11},
issn = {2045-2322},
doi = {10.1038/s41598-021-99409-3},
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.},
language = {eng},
number = {1},
journal = {Scientific Reports},
author = {Escala-Garcia, Maria and Canisius, Sander and Keeman, Renske and Beesley, Jonathan and Anton-Culver, Hoda and Arndt, Volker and Augustinsson, Annelie and Becher, Heiko and Beckmann, Matthias W. and Behrens, Sabine and Bermisheva, Marina and Bojesen, Stig E. and Bolla, Manjeet K. and Brenner, Hermann and Canzian, Federico and Castelao, Jose E. and Chang-Claude, Jenny and Chanock, Stephen J. and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and Dennis, Joe and Devilee, Peter and Dörk, Thilo and Dunning, Alison M. and Easton, Douglas F. and Ekici, Arif B. and Eliassen, A. Heather and Fasching, Peter A. and Flyger, Henrik and Gago-Dominguez, Manuela and García-Closas, Montserrat and García-Sáenz, José A. and Geisler, Jürgen and Giles, Graham G. and Grip, Mervi and Gündert, Melanie and Hahnen, Eric and Haiman, Christopher A. and Håkansson, Niclas and Hall, Per and Hamann, Ute and Hartikainen, Jaana M. and Heemskerk-Gerritsen, Bernadette A. M. and Hollestelle, Antoinette and Hoppe, Reiner and Hopper, John L. and Hunter, David J. and Jacot, William and Jakubowska, Anna and John, Esther M. and Jung, Audrey Y. and Kaaks, Rudolf and Khusnutdinova, Elza and Koppert, Linetta B. and Kraft, Peter and Kristensen, Vessela N. and Kurian, Allison W. and Lambrechts, Diether and Le Marchand, Loic and Lindblom, Annika and Luben, Robert N. and Lubiński, Jan and Mannermaa, Arto and Manoochehri, Mehdi and Margolin, Sara and Mavroudis, Dimitrios and Muranen, Taru A. and Nevanlinna, Heli and Olshan, Andrew F. and Olsson, Håkan and Park-Simon, Tjoung-Won and Patel, Alpa V. and Peterlongo, Paolo and Pharoah, Paul D. P. and Punie, Kevin and Radice, Paolo and Rennert, Gad and Rennert, Hedy S. and Romero, Atocha and Roylance, Rebecca and Rüdiger, Thomas and Ruebner, Matthias and Saloustros, Emmanouil and Sawyer, Elinor J. and Schmutzler, Rita K. and Schoemaker, Minouk J. and Scott, Christopher and Southey, Melissa C. and Surowy, Harald and Swerdlow, Anthony J. and Tamimi, Rulla M. and Teras, Lauren R. and Thomas, Emilie and Tomlinson, Ian and Troester, Melissa A. and Vachon, Celine M. and Wang, Qin and Winqvist, Robert and Wolk, Alicja and Ziogas, Argyrios and {kConFab/AOCS Investigators} and Michailidou, Kyriaki and Chenevix-Trench, Georgia and Bachelot, Thomas and Schmidt, Marjanka K.},
month = oct,
year = {2021},
pmid = {34611289},
pmcid = {PMC8492709},
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},
pages = {19787},
}

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