Impact of germline variants on breast and ovarian cancer risk in Japanese women: an original cohort study and meta-analysis
Menée à l'aide de données d'un registre hospitalier japonais portant sur 4 032 témoins, 7 220 patientes atteintes d’un cancer du sein et 2 464 patientes atteintes d’un cancer de l’ovaire, et menée à partir d'une revue systématique de la littérature portant sur 31 190 témoins et 23 193 patientes atteintes d'un cancer du sein et/ou de l'ovaire, cette méta-analyse évalue l'association entre 37 gènes de susceptibilité au cancer et le risque de développer ces 2 maladies
Background: Pathogenic variants (PVs) of BRCA1 and BRCA2 predispose individuals to a higher risk of breast and ovarian cancer; however, the precise risks posed by other cancer susceptibility genes remain unclear, particularly in Asian populations.
Methods: We executed a case–control study of 11 and 26 genes associated with breast and ovarian cancer susceptibility, respectively, in 7220 women with breast cancer, 2464 women with ovarian cancer, and 4032 controls from a multicentre, hospital-based registry in Japan. Furthermore, we conducted a meta-analysis of 23,193 patients with breast and/or ovarian cancer and 31,190 controls from six other hospital-based studies.
Findings: Overall, 395 (5.5%) patients with breast cancer and 331 (13.4%) patients with ovarian cancer harboured PVs. Meta-analyses revealed that PVs of BRCA1, BRCA2, CHEK2, PALB2, and TP53 were associated significantly with breast cancer risk (P < 0.001), while PVs of ATM, BRCA1, BRCA2, MSH6, and RAD51D were associated significantly with ovarian cancer risk (P < 0.001). PVs in the BRCA1 DNA-binding domain were associated with a younger age at diagnosis after adjusting for cancer type and family history (
β =
−3.79, 95% CI = −7.16 to −0.41; P = 0.028).
Interpretation: These results provide information about genes associated with breast and ovarian cancer risk in Asian women, as well as guidance for management of PV carriers.
eBioMedicine , article en libre accès, 2025