MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer
A partir de données de 423 femmes présentant des antécédents personnels ou familiaux de cancer du sein et porteuses de variants constitutionnels des gènes MLH1, MSH2, MSH6 ou PMS2 identifiés grâce à un test multigénique, cette étude rétrospective met en évidence le rôle, dans l'étiologie du cancer du sein, des variants de deux gènes liés à un syndrome de Lynch (MSH6 et PMS2)
Purpose : An association of Lynch syndrome (LS) with breast cancer has been long suspected; however, there have been insufficient data to address this question for each of the LS genes individually. Methods : We conducted a retrospective review of personal and family history in 423 women with pathogenic or likely pathogenic germ-line variants in MLH1 (N = 65), MSH2 (N = 94), MSH6 (N = 140), or PMS2 (N = 124) identified via clinical multigene hereditary cancer testing. Standard incidence ratios (SIRs) of breast cancer were calculated by comparing breast cancer frequencies in our study population with those in the general population (Surveillance, Epidemiology, and End Results 18 data). Results : When evaluating by gene, the age-standardized breast cancer risks for MSH6 (SIR = 2.11; 95% confidence interval (CI), 1.56–2.86) and PMS2 (SIR = 2.92; 95% CI, 2.17–3.92) were associated with a statistically significant risk for breast cancer whereas no association was observed for MLH1 (SIR = 0.87; 95% CI, 0.42–1.83) or MSH2 (SIR = 1.22; 95% CI, 0.72–2.06). Conclusion : Our data demonstrate that two LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer and should be considered when ordering genetic testing for individuals who have a personal and/or family history of breast cancer.
Genetics in Medicine 2018