Abstract. The present study aimed to investigate the association of p73 G4C14-A4T14 polymorphism and murine double minute 2 (MDM2) 309 T/G single nucleotide polymorphisms (SNPs) with the risk of developing non-small cell lung cancer (NSCLC) in Sothern China. The p73 and MDM2 genotypes of peripheral blood DNA from 186 patients with NSCLC and 196 normal controls were detected by polymerase chain reaction (PCR) with confronting two-pair primers (CTPP) and high resolution melting (HRM), respectively. The results of genotyping were consistent with those of direct sequencing. The p73 AT/AT [odds ratio (OR)=0.46; 95% confidence interval (CI)=0.22-0.97] and MDM2 TT (OR=0.48; 95% CI=0.26-0.86) genotypes were associated with a decreased risk of developing NSCLC compared with that of the p73 GC/GC and MDM2 GG genotypes, respectively. In addition, the interaction between the p73 and MDM2 polymorphisms reduced the risk of developing NSCLC in multiple ways (OR=0.13; 95% CI=0.03-0.59) for subjects carrying both the p73 AT/AT and MDM2 TT genotypes. Therefore, the SNP in p73 G4C14-A4T14 and the MDM2 309 polymorphism may be markers of genetic susceptibility to NSCLC in a Chinese population, and there is a possible gene-gene interaction involved in the incidence of NSCLC. IntroductionNon-small cell lung cancer (NSCLC), the main type of lung cancer, is one of the most common malignant tumors in males worldwide (1). The incidence and mortality of lung cancer is currently increasing in China, and the most common risk factors are involved environmental, occupational and genetic (2-4). Environmental factors, including tobacco smoking, air pollution, contamination in drinking water and food, are passing through the natural barriers such as shin and metabolic elimination; the environmental carcinogens enter cells, damage DNA and destroy the balance among growth, differentiation and apoptosis of the cells, which cause carcinogenesis (3,4).It has been well established that lung cancer is a complex disease that is highly correlated with environmental pollutants in the general population; in addition, genetic factors are known to plays an important role in this disease (2-4). Studies on the association between gene variants and lung cancer will contribute to clarify the underlying mechanisms of lung cancer, including its development, and will potentially provide therapeutic targets that are important in the diagnosis and prognosis of lung cancer.p73, one of the p53 family members, is located at the human chromosome 1p36.33, and shares relatively high structural and functional homology with p53 (5,6). As a candidate tumor-suppressor gene, it encodes two different proteins, namely the transcriptionally active full-length TAp73 and the NH 2 terminally truncated dominant-negative ΔNp73 (6), which have remarkable similarity with p53 in their DNA-binding, transactivation and oligomerization domains (5). G4C14 and A4T14, the two single nucleotide polymorphisms (SNPs) of p73 at positions 4 (G>A) and 14 (C>T) (rs2273953 and rs1801173, respectively), ...

Abstract. The p73 gene is a structural and functional homolog of the p53 gene, which has a crucial role in mediating cell cycle arrest and apoptosis. Numerous previous studies have investigated the polymorphism of p73 G4C14-to-A4T14 at exon 2, as it was suggested to affect gene expression and result in functional significance. However, the correlation of this polymorphism with clinicopathological variables of patients with non-small cell lung cancer (NSCLC) remains to be elucidated. The aim of the present study was to examine the association between the gene polymorphism of p73 G4C14-to-A4T14 and the risk of developing NSCLC. The single-nucleotide polymorphisms of p73 G4C14-to-A4T14 were genotyped using polymerase chain reaction with confronting two-pair primers and direct DNA sequencing in 186 NSCLC patients and 196 cancer-free controls. χ 2 -tests and logistic regression analysis were used to analyze the experimental data, including the determination of odds ratio (OR), 95% confidence intervals (95% CIs) and P-values. The results demonstrated that the AT/AT genotype was associated with a significantly decreased risk of NSCLC (P= 0.010; OR= 0.370; 95% CI= 0.170-0.806) compared with the GC allele genotypes including GC/GC and GC/AT. In addition, carriers of the AT allele exhibited a significantly reduced risk of NSCLC (P= 0.038; OR= 0.713; 95% CI= 0.517-0.983) compared with non-carriers. In conclusion, these results indicated that the p73 G4C14-to-A4T14 polymorphism was a potential marker of NSCLC genetic susceptibility. However, further studies with a larger population are required in order to confirm these results.