Male breast cancer risk associated with pathogenic variants in genes other than BRCA1/2: an Italian case-control study.

Humans Female Male Breast Neoplasms, Male / genetics Genetic Predisposition to Disease Case-Control Studies Breast Neoplasms / genetics Genes, BRCA1 Risk Assessment

ATM BRCA1/2 Breast cancer risk CHEK2 Case-control study Male breast cancer Multigene panel testing PALB2 Pathogenic variants

Journal

European journal of cancer (Oxford, England : 1990)

ISSN: 1879-0852

Titre abrégé: Eur J Cancer

Pays: England

ID NLM: 9005373

Informations de publication

Date de publication:
07 2023

Historique:

received: 06 02 2023

revised: 24 04 2023

accepted: 26 04 2023

medline: 19 6 2023

pubmed: 2 6 2023

entrez: 1 6 2023

Statut: ppublish

Résumé

Germline pathogenic variants (PVs) in BRCA1/2 genes are associated with breast cancer (BC) risk in both women and men. Multigene panel testing is being increasingly used for BC risk assessment, allowing the identification of PVs in genes other than BRCA1/2. While data on actionable PVs in other cancer susceptibility genes are now available in female BC, reliable data are still lacking in male BC (MBC). This study aimed to provide the patterns, prevalence and risk estimates associated with PVs in non-BRCA1/2 genes for MBC in order to improve BC prevention for male patients. We performed a large case-control study in the Italian population, including 767 BRCA1/2-negative MBCs and 1349 male controls, all screened using a custom 50 cancer gene panel. PVs in genes other than BRCA1/2 were significantly more frequent in MBCs compared with controls (4.8% vs 1.8%, respectively) and associated with a threefold increased MBC risk (OR: 3.48, 95% CI: 1.88-6.44; p < 0.0001). PV carriers were more likely to have personal (p = 0.03) and family (p = 0.02) history of cancers, not limited to BC. PALB2 PVs were associated with a sevenfold increased MBC risk (OR: 7.28, 95% CI: 1.17-45.52; p = 0.034), and ATM PVs with a fivefold increased MBC risk (OR: 4.79, 95% CI: 1.12-20.56; p = 0.035). This study highlights the role of PALB2 and ATM PVs in MBC susceptibility and provides risk estimates at population level. These data may help in the implementation of multigene panel testing in MBC patients and inform gender-specific BC risk management and decision making for patients and their families.

Sections du résumé

BACKGROUND

METHODS

We performed a large case-control study in the Italian population, including 767 BRCA1/2-negative MBCs and 1349 male controls, all screened using a custom 50 cancer gene panel.

RESULTS

PVs in genes other than BRCA1/2 were significantly more frequent in MBCs compared with controls (4.8% vs 1.8%, respectively) and associated with a threefold increased MBC risk (OR: 3.48, 95% CI: 1.88-6.44; p < 0.0001). PV carriers were more likely to have personal (p = 0.03) and family (p = 0.02) history of cancers, not limited to BC. PALB2 PVs were associated with a sevenfold increased MBC risk (OR: 7.28, 95% CI: 1.17-45.52; p = 0.034), and ATM PVs with a fivefold increased MBC risk (OR: 4.79, 95% CI: 1.12-20.56; p = 0.035).

CONCLUSIONS

This study highlights the role of PALB2 and ATM PVs in MBC susceptibility and provides risk estimates at population level. These data may help in the implementation of multigene panel testing in MBC patients and inform gender-specific BC risk management and decision making for patients and their families.

Identifiants

DOI: 10.1016/j.ejca.2023.04.022 PMID: 37262986

pubmed: 37262986

pii: S0959-8049(23)00222-8

doi: 10.1016/j.ejca.2023.04.022

pii:

doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

183-191

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.