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Common Susceptibility Loci for Male Breast Cancer

Maguire, Sarah ; Olsson, Håkan LU orcid ; Hedenfalk, Ingrid LU orcid and Orr, Nick (2021) In Journal of the National Cancer Institute 113(4). p.453-461
Abstract
Background
The etiology 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 of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC.

Methods
We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate... (More)
Background
The etiology 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 of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC.

Methods
We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10–06. Genetic correlation with FBC was evaluated using linkage disequilibrium 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 and MBC. All statistical tests were 2-sided.

Results
The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10–08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor–positive FBC. Men in the top quintile of genetic risk had a fourfold 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 × 10–30).

Conclusions
These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men. (Less)
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author
; ; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the National Cancer Institute
volume
113
issue
4
pages
9 pages
publisher
Oxford University Press
external identifiers
  • scopus:85102459182
  • pmid:32785646
ISSN
1460-2105
DOI
10.1093/jnci/djaa101
language
English
LU publication?
yes
id
b12f008c-de3f-429d-9086-44b1f0a3b880
date added to LUP
2022-02-08 12:44:01
date last changed
2025-10-14 10:09:33
@article{b12f008c-de3f-429d-9086-44b1f0a3b880,
  abstract     = {{Background<br/>The etiology 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 of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC.<br/><br/>Methods<br/>We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10–06. Genetic correlation with FBC was evaluated using linkage disequilibrium 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 and MBC. All statistical tests were 2-sided.<br/><br/>Results<br/>The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P &lt; 5 × 10–08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor–positive FBC. Men in the top quintile of genetic risk had a fourfold 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 × 10–30).<br/><br/>Conclusions<br/>These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.}},
  author       = {{Maguire, Sarah and Olsson, Håkan and Hedenfalk, Ingrid and Orr, Nick}},
  issn         = {{1460-2105}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{453--461}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of the National Cancer Institute}},
  title        = {{Common Susceptibility Loci for Male Breast Cancer}},
  url          = {{http://dx.doi.org/10.1093/jnci/djaa101}},
  doi          = {{10.1093/jnci/djaa101}},
  volume       = {{113}},
  year         = {{2021}},
}