The Ner Pathway Genes And Susceptibility To Lung Cancer Association Study

Lung cancer is one of the most serious types of malignant tumors. With a high incidence and mortality rates, lung cancer causes more than 1. 3 million deaths every year. In China, the incidence of lung cancer in male and female is 42. 4/100, 000 and 19. 0/100, 000 separately. And the mortality rate in China is 20/100, 000, higher than the mean in developed countries and developing countries. Although tobacco use is considered the leading cause of lung caner, the interactions between genes and environment are involved in the occurrence and developing of lung cancer. Metabolism genes and DNA repair genes are the 2 groups of genes involved in lung cancer genesis.We selected 40 SNPs on 8 genes in nucleotide excision repair pathway in a case-control study of 1010 incident lung cancer and 1011 cancer-free control in a Chinese Han population.5 loci were discovered statistically significant associated with the incidence of lung cancer, containing ERCCl-rs3212948, ERCC4-rs3136038, ERCC5-rs4150306, DDB2-rs830083 and XPC-rs3731055 (P (0.05). Adjusted with environment confusion factors including packyear, family history of cancer, age and gene with multivariant logistic regression, we found that rs3212948, rs830083 and rs3731055 fit for dominant model, while rs3136038 fit for additive model and rs4150306 fit for recessive model.The minor allele carriers on ERCCl-rs3212948 and the heterozygout of ERCC4-rs3136036 appears a significant resistance to lung cancer, (rs3212948 (GC+CC): adjusted OR (95% CI) = 0.76(0. 63-0. 91)) , P=0. 003) ; (rs3136038 (CT) : adjusted OR (95% CI) =0.74(0.61-0.90), P=0.002) . While the Odds Ratio significantly increased for the homozygote of ERCC5-rs4150306 and the minor allele carriers on DDB2-rs830083.In a stratification study, we found that the genetic factors had a statistically significant interaction with the environment exposure factors. Significant association between polymorphisms in NER pathway and primary lung cancer was observed in the individuals without family history of cancer. Furthermore, some genotypes in NER pathway would indicate an early-onset incidence of primary lung cancer.A pairwise analysis between genotypes of the polymorphism revealed a significant interaction among ERCC1, ERCC4 and the function-unclear DDB2 genes. The combination of the two major allele homozygotes on ERCCl-rs3212948 and ERCC4-rs3136038 indicated an increased risk of 50% to lung cancer, while the other two combination, heterozygote on ERCC1 or ERCC4 with the minor allele homozygotes, decreased risk of lung cancer.And genetic factors are associated with the early-onset of the lung cancer. Additionally, when environmental pressure decreased, the effects of genetic factors would be enhanced.Furthermore, based on the EGP database of resequencing dataset of 90 ethnic-mixed individuals, we explored the potential functional loci with high LD with our positive SNPs. Further studies on molecular functional exploration and on epidemiology in large diverse ethnic population were warranted.