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Phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog 1 (AKT1), mouse double minute 2 (MDM2) and p53 play important roles in the development of cancer. We examined whether the single nucleotide polymorphisms (SNPs) in the  PTEN ,  AKT1 ,  MDM2  and  p53  genes were related to the risk and severity of nasopharyngeal carcinoma (NPC) in the Chinese population. Seven SNPs [ p53  rs1042522,  PTEN  rs11202592,  AKT1  SNP1-5 (rs3803300, rs1130214, rs3730358, rs1130233 and rs2494732)] were genotyped in 593 NPC cases and 480 controls by PCR direct sequencing or PCR-RFLP analysis. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). None of the polymorphisms alone was associated with the risk or severity of NPC. However, haplotype analyses indicated that a two-SNP core haplotype (SNP4-5, AA) in  AKT1  was associated with a significantly increased susceptibility to NPC risk (adjusted OR  =  3.87, 95% CI  =  1.96–7.65;  P <0.001). Furthermore, there was a significantly increased risk of NPC associated with the combined risk genotypes (i.e.,  p53  rs1042522 Arg/Pro + Pro/Pro,  MDM2  rs2279244 G/T + G/G,  PTEN  rs11202592 C/C,  AKT1  rs1130233 A/A). Compared with the low-risk group (0–2 combined risk genotypes), the high-risk group (3-4 combined risk genotypes) was associated with a significantly increased susceptibility to NPC risk (adjusted OR  =  1.67, 95% CI  =  1.12–2.50;  P  = 0.012). Our results suggest that genetic variants in the PTEN, AKT1, MDM2 and p53 tumor suppressor-oncoprotein network may play roles in mediating the susceptibility to NPC in Chinese populations.

Combined Effects of Genetic Variants of the PTEN, AKT1, MDM2 and p53 Genes on the Risk of Nasopharyngeal Carcinoma