A meta-analysis of TP53 codon 72 polymorphism and lung cancer risk: Evidence from 15,857 subjects

The genetic polymorphism of TP53 codon 72 is thought to have significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 23 published studies involving 15,857 subjects of the association between TP53 codon 72 polymorphism and risk of lung cancer. For the homozygote Pro/Pro and Pro allele carriers (Pro/Pro + Pro/Arg), the ORs for all studies combined (7495 cases and 8362 controls) were 1.221 (95% CI = 1.046–1.425; P = 0.021 for heterogeneity) and 1.148 (95% CI = 1.040–1.266; P = 0.008 for heterogeneity). In the stratified analysis by ethnicity, significantly increased risks were found in Asians (3254 cases and 3350 controls) for both the homozygote Pro/Pro (OR = 1.395; 95% CI = 1.206–1.613; P = 0.806 for heterogeneity) and the Pro allele carriers (OR = 1.109; 95% CI = 1.000–1.228; P = 0.458 for heterogeneity). In Caucasians (3359 cases and 3953 controls), significantly elevated risk was associated with Pro allele carriers (OR = 1.180; 95% CI = 1.029–1.353; P = 0.073 for heterogeneity). In the subgroup analyses by pathological type, the ORs for the homozygote Pro/Pro and Pro allele carriers were 1.289 (95% CI = 1.027–1.618; P = 0.096 for heterogeneity) and 1.168 (95% CI = 1.062–1.284; P = 0.231 for heterogeneity) for lung adenocarcinoma (2724 cases and 6591 controls). When stratified by smoking status, the pooled OR was 1.440 (95% CI = 1.078–1.923; P = 0.042 for heterogeneity) for the Pro allele carriers among smokers (1480 cases and 1414 controls). Although some statistical bias could not be eliminated, this meta-analysis suggests that the Pro allele is a low-penetrant risk factor for developing lung cancer. Additionally, we found that this phenomenon was more prominent in subgroups such as in Asians and Caucasians, in lung adenocarcinoma, or in smokers.