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

Abstract

Background: The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.

Methods: 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.

Results: 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).

Conclusion: The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.

Figure 1

Representative PCR-RFLP for different genotypes containing the TP53 Arg72Pro polymorphism site and DNA sequencing analysis. (A) M: DNA size markers; lane 1, 2, 4 and 5: TP53 72Pro/Pro; lane 6, 7 and 8: TP53 72Arg/Pro; lane 3: TP53 72Arg/Arg. (B) The PCR products with different PCR-RFLP profiles were sequenced to confirm the genotypes.

Figure 2

Representative tetraprime ARMS-PCR for different genotypes containing the MDM2 SNP309 T>G polymorphism site and DNA sequencing analysis. (A) M: DNA size markers; lane 1, and 9: MDM2 309TT; lane 2, 3, 4, 6 and 8: MDM2 309TG; lane 5 and 7: MDM2 309TT. (B) The PCR products with different tetraprime ARMS-PCR profiles were sequenced to confirm the genotypes.

Figure 3

MDM2 mRNA expression level in NPC tissue as function of MDM2 genotype. Columns, mean; bars, ± SD normalized to β-actin. Expression level among the GG genotype was significantly different from that among the GT or TT genotype (P < 0.05).