The Association Between VDR and GC Polymorphisms and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Lung cancer is the leading cause of cancer-related deaths worldwide, imposing an enormous economic burden on society. Several studies have identified a link between the genetic polymorphisms in vitamin D pathways and lung cancer risk; however, the results remain inconclusive. The aim of this study was to estimate the effect of polymorphisms in the vitamin D receptor (VDR) and GC genes on lung cancer risk. Eligible case-control studies published between January 2000 and December 2018 were searched and studied. The pooled odds ratio and its 95% confidence interval were used to estimate the effect. Fifteen articles that included 4732 lung cancer patients and 4337 controls were identified for this study. Our results demonstrated that the VDR Bsm1 polymorphism (p < 0.05) and the TC and TT+TC genotypes of the Cdx2 polymorphism (p < 0.05) were protective factors for avoiding lung cancer incidence, while the T allele and the TT genotype of Taq1 polymorphism (p < 0.05) were risk factors for lung cancer. Ethnicity-based subgroup analyses indicated that the AA genotype of both the Apa1 and the Bsm1 polymorphisms decreased lung cancer risk in Asians, while Fok1 and Taq1 polymorphisms increased lung cancer risk in Asians. Subgroup analysis by cancer subtypes showed that certain alleles and genotypic structures of the Bsm1, Fok1, Taq1, and rs7041 were associated with nonsmall-cell lung cancer risk. Subgroup analysis by smoking status showed that the interaction between the TT genotype of Taq1 and smoking increased the risk of lung cancer. Subgroup analysis with regard to gender showed that the AA+Aa genotype of Apa1 decreased lung cancer risk in male patients. Our results suggest that the Bsm1 and Cdx2 polymorphisms decreased lung cancer risk, while the Taq1 polymorphism increased lung cancer risk. Moreover, the AA genotype of the Apa1 and Bsm1 variants were protective factors in Asian populations, whereas the Fok1 and Taq1 polymorphisms were risk factors for lung cancer in Asian populations. Future case-control studies with different ethnicities are still needed to generalize these associations.