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

Background: Lung cancer is the leading cause of cancer-related death 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. Methods: 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. Results: 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 T allele and TT genotype of Taq1 polymorphism ( p  < 0.05) were risk factors for lung cancer. Ethnicity-based subgroup analysis indicated that the AA genotype of the Apa1 , alleles, and genotypes of Bsm1 polymorphism decreased lung cancer risk in Asians, while Fok1 and Taq1 polymorphisms increased lung cancer risk in Asians. Subgroup analysis by the cancer subtypes showed that allele and/or genotype of Bsm1 , Fok1 , Taq1 , and rs7041 were associated with nonsmall-cell lung cancer risk. Subgroup analysis by smoking status showed that the interaction between TT genotype of Taq1 and smoking increased the risk of lung cancer. Subgroup analysis with regard to gender showed that AA+Aa genotype of Apa1 decreased lung cancer risk in male patients. Conclusions: Our results suggested that the Bsm1 and Cdx2 polymorphisms decreased lung cancer risk, while 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.