Gene Variations In Cell Cycle Regulatory Genes And Risk And Prognosis Of Laryngeal Carcinoma

Background & Aims:Cell cycle regulatory genes play important roles in cancer development. Tumor suppressor gene TP53 is the key one, Which can activate and regularize other cell cycle regulatory genes to take effect. MDM2 is the main negative regulator of TP53, and the MDM2 variation may lead to increased risk to develop malignant tumors. This study was to explore the association between MDM2 SNPs. alone and in combination with TP53 and risk of the occurrence and prognosis of laryngeal cancer in Han Chinese population.Methods:we conducted a case-control study to examine the hypothesis that MDM2 and TP53 gene SNPs might be associated with risk of the occurrence and prognosis of laryngeal cancer. MALDI-TOF MS was performed to determine the genotypes of 251 patients with laryngeal cancer, and 365 controls. Comparing the gender, age, smoking situation and distribution of different genetypes by x2 test. odds ratios and 95% confidence intervals were estimated by logistic regression. Analyzing follow-up materials by Kaplan-Meier curve and cox regression.Results:On the basis of analysis of 251 laryngeal cancer cases,365 controls, the distribution of genotypes of 2 genetic variants in cases and controls was consistent with Hardy-Weinberg equilibrium. Smokers rates in cases and controls were 85.1% and 43.8%, respectively (p<0.001). We observed smoking can significantly increase risk of developing laryngeal cancer(OR=9.75,95% CI 6.36-14.95), and heavy smoking may cause higher increased risk(OR=13.12,95% CI 8.16-23.10). No significant association was detected between MDM2 309G>T and TP53 Arg72pro SNPs and the risk of laryngeal cancer (p>0.05). But in non-smoking subjects, GT or GG genotypes had an overall 4-fold(95% CI 1.07-14.87) and 4.8-fold (95% CI 1.37-16.92) increased risk for developing laryngeal cancer, compared with the TT genotype, respectively. Subjects with the Arg72Pro genotype had an decreased risk for lymphnodes metastasis(OR=0.48,95% CI 0.25-0.92, P=0.027)compared with those with the Arg72Arg genotype. Survival analyses showed that a significant association existed between the two variants and prognosis of laryngeal cancer. The 5-year-survival of the GG or Pro/Pro gene type were significantly lower than other genotypes of respective gene(5-year-survival of G/G,G/T and T/T was 45.8%,64.3%,67.1%, respectively, p=0.024; 5-year-survival of pro/pro, Arg/pro and Arg/Arg was 47.1% 65.3% 57.2%, respectively, p=0.049). The interaction of MDM2 and TP53 polymorphisms increased the risk of poor prognosis in a super-multiplicative manner (OR for the presence of both MDM2 GG and P53 Pro/Pro genotypes was 3.35,95% CI 1.49-7.54).Conclusion:MDM2 309G>T and TP53 Arg72pro SNPs play an important role in laryngeal cancer development.