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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/124208

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

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Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease(1). We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 x 10(-8) with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

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LÁZARO GARCÍA, Conxi, ProCURE and GENETIC COUNSELING UNIT, Hereditary Cancer Program. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics. 2017. Vol. 49, num. 12, pags. 1767-1778. [consulted: 10 of June of 2026]. Available at: https://hdl.handle.net/2445/124208

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