Association of p73 gene G4C14-A4T14 polymorphism and MDM2 gene SNP309 with non-small cell lung cancer risk in a Chinese population

Abstract

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), ...

Association between p73 G4C14‐to‐A4T14 polymorphism and lung cancer risk: A systematic review and meta‐analysis

“…The literature search resulted in the identification of 239 documents: 78 studies were excluded after duplicates were removed, and 112 papers were excluded after review of titles and abstracts. The full text of the 49 remaining publications was screened, and, finally, nine studies including 3543 cases and 4435 control individuals were included 18–22,35–38 . The flow chart of the meta‐analysis is shown in Figure 1.…”

The cell cycle regulatory gene polymorphisms TP53 (rs1042522) and MDM2 (rs2279744) in lung cancer: a meta-analysis

“…Data on the contribution of MDM2 SNP309 to the development of lung cancer are very contradictory. Most studies have shown an association of the MDM2 (rs2279744) mutant allele with a high risk of lung tissue carcinogenesis (Enokida et al, 2014;Wang X. et al, 2015;Li, 2017). However, Pine et al (2006) did not find that MDM2 SNP309 is associated with lung neoplasia in the European population.…”

Interaction between common variants of MDM2 and PPP1R13L and CD3EAP and TP53 SNPs in relation to lung cancer risk among Chinese

“…nih.gov/gene/4193) (3). The effects of single nucleotide polymorphisms (SNP) at MDM2 have been investigated in relation to lung cancer with inconsistent results (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…Previous epidemiology studies concerning MDM2 SNPs and lung cancer risk were mainly focused on single SNP and interactions (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). No systematical investigations have been reported on the associations between MDM2 htSNPs (Haplotype-tagging SNP) and lung cancer risk.…”