Common susceptibility loci for male breast cancer

Sarah Maguire, Eleni Perrakis, Katarzyna Tomczyk, Michael Jones, Olivia Fletcher, Matthew Pugh, Timothy Winter, Kyle Thompson, Rosie Cooke, Alison H Trainer, James Paul, Stig E Bojesen, Henrik Flyger, Heli Nevanlinna, Johanna Mattson, Eitan Friedman, Yael Laitman, Domenico Palli, Giovanna Masala, Ines ZannaLaura Ottini, Valentina Silvestri, Antoinette Hollestelle, Maartje J Hooning, Srdjan Novaković, Mateja Krajc, Manuela Gago-Dominguez, Jose Esteban Castelao, Håkan Olsson, Ingrid Hedenfalk, Emmanouil Saloustros, Vasilios Georgoulias, Douglas F Easton, Paul Pharoah, Alison M Dunning, D Timothy Bishop, Susan L Neuhausen, Linda Steele, Alan Ashworth, Montserrat García-Closas, Richard Houlston, Anthony J Swerdlow, Nick Orr*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
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The aetiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study (GWAS) of MBC identified two predisposition loci for the disease, both of which were also associated with risk of FBC.


We performed genome-wide single nucleotide polymorphism (SNP) genotyping of European ancestry MBC case subjects and controls, in three stages. Associations between directly genotyped and imputed SNPs with MBC were assessed using fixed-effects meta-analysis of 1,380 cases and 3,620 controls. Replication genotyping of 810 cases and 1,026 controls was used to validate variants with P-values < 1 x 10-06. Genetic correlation with FBC was evaluated using LD score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score (PRS) and MBC. All statistical tests were two-sided.


The GWAS identified three novel MBC susceptibility loci that attained genome-wide significance (P < 5 x 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen-receptor (ER) positive FBC. Males in the top quintile of genetic risk had a four-fold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 x 10-30).


These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic aetiology with FBC and identifying a four-fold high risk group of susceptible men.

Original languageEnglish
Article numberdja101
JournalJournal of the National Cancer Institute
Early online date12 Aug 2020
Publication statusEarly online date - 12 Aug 2020


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