Abstract:Background: More than half of the families with breast and/or ovarian cancer (BC/OC) have no BRCA1 or BRCA2 mutation, moreover the broad lifetime risks reported within families with a BRCA1/2 mutation suggest other genes are also responsible.Objective: Assess the prevalence, gene-gene and phenotype-genotype associations of two functional progesterone receptor polymorphisms (PRP), PROGINS and +331G/A, in familial BC/OC.Methods: DNA samples from 318 randomly selected probands tested for BRCA1/2 mutations were genotyped for the PRP and CHEK2*1100delC variant.Results: BRCA1 was associated with BC at young age, p=0.002; +331A marginally with OC, p=0.07, and PROGINS with male BC, p=0.04. Homozygous +331A/A co-segregated with BRCA2 variants more frequently than expected by chance alone. Co-occurrence of +331A with a BRCA1BRCA2 mutation was associated with multiple BC events compared to +331A or BRCA1/BRCA2 alone, p=0.02.Conclusions: The PRP are risk factors for familial BC/OC, and +331A allele is a gene modifier of BRCA1 and BRCA2.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.