The Association Between and 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 () and 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 polymorphism ( < 0.05) and the TC and TT+TC genotypes of the polymorphism ( < 0.05) were protective factors for avoiding lung cancer incidence, while the T allele and the TT genotype of polymorphism ( < 0.05) were risk factors for lung cancer. Ethnicity-based subgroup analyses indicated that the AA genotype of both the and the polymorphisms decreased lung cancer risk in Asians, while and polymorphisms increased lung cancer risk in Asians. Subgroup analysis by cancer subtypes showed that certain alleles and genotypic structures of the , , , and rs7041 were associated with nonsmall-cell lung cancer risk. Subgroup analysis by smoking status showed that the interaction between the TT genotype of and smoking increased the risk of lung cancer. Subgroup analysis with regard to gender showed that the AA+Aa genotype of decreased lung cancer risk in male patients. Our results suggest that the and polymorphisms decreased lung cancer risk, while the polymorphism increased lung cancer risk. Moreover, the AA genotype of the and variants were protective factors in Asian populations, whereas the and polymorphisms were risk factors for lung cancer in Asian populations. Future case-control studies with different ethnicities are still needed to generalize these associations.