Relationship Between and Mutations and MRNA Expression in Breast and Ovarian Cancer Predisposition

The aetiology of breast and ovarian cancer (BC/OC) is multi-factorial. At present, the involvement of base excision repair (BER) glycosylases (MUTYH and OGG1) in BC/OC predisposition is controversial. The present study investigated whether germline mutation status and mRNA expression of two BER genes, and , were correlated with in 59 patients with BC/OC and 50 matched population controls. In addition, to evaluate the relationship between , and , their possible mutual modulation and correlation among mutational spectrum, gene expression and demographic characteristics were evaluated. The results identified 18 and variants, of which 4 were novel (2 and 2 ) in 44 of the 59 patients. In addition, two pathogenic mutations were identified: p.Arg46Gln, detected in a patient with BC and a family history of cancer, and p.Val234Gly in a patient with OC, also with a family history of cancer. A significant reduced transcript expression in was observed P=0.033) in cases, and in association with the presence of rare variants in the same gene (P=0.030). A significant correlation in the expression of the two BER genes was observed in cases (P=0.004), whereas OGG1 and BRCA1 was significantly correlated in cases (P=0.001) compared with controls (P=0.010). The results of the present study indicated that the relationship among mutational spectrum, gene expression and demographic characteristics may improve the genetic diagnosis and primary prevention of at-risk individuals belonging to families with reduced mRNA expression, regardless of mutation presence.