Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.As an important tumor suppressor, TP53 protein level is low or undetectable in normal cells, but diverse forms of stress may trigger its production, resulting in either cell cycle arrest or apoptotic cell death [1,2]. High frequencies of TP53 mutation and/or deletion are found in a wide variety of human malignancies, including nasopharyngeal carcinoma (NPC), which is believed to be contributed to tumorigenesis and progression [3-5].Recently, Bond et al. reported that a T>G polymorphism at position 309 downstream from MDM2 intron 1 disrupts an Sp1 regulatory element and the T allele thus has a strikingly lower promoter activity compared with the G allele [6]. Moreover, a single nucleotide polymorphism has been identified in the coding region of TP53, which causes an Arg72>Pro amino acid substitution [7]. It has been shown that, compared with Pro allele, the Arg allele is faster to induce apoptosis and more efficient in suppressing transformation. Many molecular epidemiologic data found that these two polymorphisms are likely candidate genetic markers of certain cancers [8-10]. However, the gene-gene interaction of these two polymorphisms in MDM2 and TP53 has not been examined in NPC studies to date. Because of t