Common Susceptibility Loci for Male Breast Cancer
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/b12f008c-de3f-429d-9086-44b1f0a3b880
- author
- Maguire, Sarah ; Olsson, Håkan LU ; Hedenfalk, Ingrid LU and Orr, Nick
- author collaboration
- organization
- publishing date
- 2021
- 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
- 2022-04-26 03:36:44
@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 < 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}}, }