Impact on breast cancer susceptibility and clinicopathological traits of common genetic polymorphisms in TP53, MDM2 and ATM genes in Sardinian women

Common variants of genes involved in DNA damage correction [tumor protein p53 (TP53), murine double 2 homolog oncoprotein (MDM2) and ataxia‑telengiectasia mutated (ATM)] may serve a role in cancer predisposition. The purpose of the present study was to investigate the association of five variants in these genes with breast cancer risk and clinicopathological traits in a cohort of 261 women from northern Sardinia. Polymorphic variants in TP53 (rs17878362, rs1042522 and rs1625895), MDM2 (rs2279744) and ATM (rs1799757) were determined by PCR and TaqMan single nucleotide polymorphism assay in patients with breast cancer (n=136) and healthy controls (n=125). Association with clinicopathological (e.g., age at diagnosis, lymph node involvement, clinical stage) and lifestyle factors (e.g., smoking status, alcohol intake, contraceptive use) was also evaluated. TP53 rs17878362 and rs1625895 polymorphisms were associated with decreased risk of BC diagnosis in patients older than 50 years (codominant and recessive models) and post‑menopause (recessive model). Furthermore, there was a significant association between lymph node status (positive vs. negative) and ATM rs1799757‑delT in dominant and additive models and between MDM2 rs2279744‑allele and use of oral contraceptives. This analysis suggested that TP53 rs17878362 and rs1625895 may affect age of onset of breast cancer and ATM rs1799757 and MDM2 rs2279744 may be associated with lymph node status and prolonged use of oral contraceptives, respectively.