Association of p73 G4C14-to-A4T14 polymorphism with non-small cell lung cancer risk

Abstract

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.

Association between TP73 G4C14-A4T14 polymorphism and different cancer types: an updated meta-analysis of 55 case–control studies

“…However, some studies found that this variant was associated with a reduced risk of NSCLC in AT/AT carriers compared with GC/GC carriers. 43,45,47,59,60,64,71 In contrast, other studies showed that this polymorphism could significantly increase the risk of NSCLC among the variant GC/AT and AT/AT genotype carriers, and a high GC content increased the risk. TP73 and MDM2 variants jointly increase the risk of lung cancer, depending on the number of variant alleles.…”

“…Fifty-five case–control studies 2 , 24 – 74 including 15,648 cancer cases and 19,159 controls met the eligibility criteria and were finally included in this meta-analysis ( Figure 1 ). A total of 194 studies were excluded after screening the title, abstract and full-text, because of irrelevant information, incomplete genetic data, or duplicate contents.…”

“…Given its ability to modify the tumor suppression activity of TP73 , the association between G4C14-A4T14 and carcinogenesis has recently been investigated in genome-wide association studies in multiple cancer types, including lung, colorectal, breast, cervical, gastric, esophageal, endometrial, oral, and ovarian cancer, in addition to head and neck squamous cell carcinoma, lymphoma, and cutaneous melanoma. 2 , 24 – 74 However, the findings of these studies were inconsistent. Although previous meta-analyses have summarized the evidence regarding the roles of the G4C14-A4T14 polymorphism in different cancers, the numbers of studies included in those meta-analyses were limited, 75 – 78 While a larger sample size provides firmer evidence in population-based genetic association studies.…”

Relationship of p73 gene polymorphism and additional gene-smoking and gene-obesity interaction with non-small cell lung cancer risk

“…Up to now, we found limited human population study investigating the relationship between G4C14-to-A4T14 polymorphism and NSCLC risk. Wang et al [ 13 ] indicated that the distribution for G4C14-to-A4T14 genotype was significantly different between NSCLC cases and controls. The sample in this study was relative small, so the results obtained from this study should be checked in other studies with larger sample.…”

“…Recently, a kind of polymorphism involves two single-nucleotide polymorphisms (SNPs) at positions 4 (G-A) and 14 (C-T) (G4C14-to-A4T14) were more reported [ 8 ]. Several previous studies have indicated the association between G4C14-to-A4T14 and NSCLC risk in different populations [ 13 – 15 ]; however, they concluded inconsistent results. In addition, more and more evidence suggested that lung cancer was significantly associated with both genetic factor and environmental factors in the general population.…”