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

Abstract

Common variants of genes involved in DNA damage correction [tumor protein p53 (<em>TP53</em>), murine double 2 homolog oncoprotein (<em>MDM2</em>) and ataxia‑telengiectasia mutated (<em>ATM</em>)] 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 <em>TP53</em> (rs17878362, rs1042522 and rs1625895), <em>MDM2</em> (rs2279744) and <em>ATM</em> (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. <em>TP53</em> 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 <em>ATM</em> rs1799757‑delT in dominant and additive models and between <em>MDM2</em> rs2279744‑allele and use of oral contraceptives. This analysis suggested that <em>TP53</em> rs17878362 and rs1625895 may affect age of onset of breast cancer and <em>ATM</em> rs1799757 and <em>MDM2</em> rs2279744 may be associated with lymph node status and prolonged use of oral contraceptives, respectively.