A single-nucleotide polymorphism in the TP53 and MDM-2 gene modifies breast cancer risk in an ethnic Arab population

Abstract

Breast cancer is the most common oncological disease in women worldwide. Genetic predisposition to breast cancer can be associated with single-nucleotide polymorphisms (SNPs), which are observed in many women. Such gene polymorphisms, in combination with nutritional and environmental factors, can affect breast cancer development. The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies have revealed that TP53 72Arg > Pro and MDM2 309T > G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and breast cancer susceptibility in the Saudi population has not been explored. In this study, we performed a case-control study of patients with breast cancer and healthy controls in a Saudi population using TaqMan-based real-time PCR. We found an increased breast cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 2.04-3.92] and TG [OR = 1.43, 95% CI = 1.12-2.02] genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.19, 95% CI = 1.54-3.06) compared with the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased breast cancer risk in a multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.71, 95% CI = 3.49-17.54). These findings suggest that polymorphisms of MDM2 and TP53 genes may be a genetic modifier for developing breast cancer in this ethnic population in the Arab world.