The Association Of CFH Variant With The Risk Of Small Cell Lung Cancer

Worldwide, lung cancer has become the major cause of cancer death. The incidence of lung cancer is still on the rise. There are two types of Lung cancer, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). SCLC making up about25%of all lung cancer cases is a fast-growing type and has a poor prognosis. Evidences showed that the development of lung cancer was associated with individual genetic variants of cancer-related genes.The complement system played an important role in innate immunity and further contributed to the development of several cancers. The activation of complement provides effective ways for the destruction of invading microorganisms, clearance of immune complexes and elimination of dead and apoptotic cells. Complement cascade is activated via three distinct pathways: the classical, the alternative and the lectin pathway. The common step of three pathways are the cleavage and activation of C3, which results in the deposition of C3b on the surface of the malignant cells to form the membrane attack complex (MAC) and further disrupt the membrane’s integrity and facilitate cell lysis. Study showed that complement played an important role in controlling tumor growth. Studies have shown that non-small cell lung cancer cells constitutively expressed and secreted complement factor H and the expression of the complement inhibitor factor H could prevent complement activation and further improve tumor development.Objective:This study was aimed to explore the relationship between genetic variants in CFH and the susceptibility to small cell lung cancer (SCLC) in Chinese population. The study provided important stuff for early detection and early diagnosis of lung cancer. Methods:A case-control study was used on association between CFH and lung cancer susceptibility. We recruited145hospital based small cell lung cancer cases and435normal controls from Tangshan City. Statistical analyses were performed using the SPSS16.0statistical software package. The χ2test was used to examine differences in demographic variables and smoking status between patients and controls. We used Haploview4.2program to select17SNPs of CFH. All genotypes of CFH were determinded with iPlex Gold Genotyping Assay and Sequenom MassArray. Epidemiological data of each participant were collected by making medical records. The association of CFH genotypes with the risk of small cell lung cancer was estimated by odds ratios (ORs) and95%confidence interval (95%CI) using unconditional logistic regression models adjusting for sex, age, and smoking status.Results:The case-control study consisted of145patients with small cell lung cancer and435cancer-free controls. There were no statistically significant differences in the distributions of sex, age, and smoking status. Furthermore, for heavy smokers, the cases involved in34.5%smokers over25pack-years; however, controls just had18.2%,indicating that the difference between the cases and concrols were statistically significant(P<0.001). Based on the Chinese population data from HapMap database, candidate tag SNPs were selected. When selecting tag SNPs, we used Haploview4.2program. A total of17SNPs of CFH (rs1065489, rs12144939, rs1831281, rs4658046, rs6695321, rs7524776, rs1061170, rs10733086, rs1329428, rs3753394, rs3766404, rs800292, rs10922096, rsl1582939, rs2019727, rs505102, rs6680396) were selected for further genotyping.In present study, we investigated the association of17tag SNPs of CFH with the risk of small cell lung cancer. We found that CFH rs7524776polymorphism was related to the risk of small cell lung cancer. The results showed that the carriers with rs7524776CT genotype had an increased risk of small cell lung cancer (OR=2.21,95%CI=1.26-3.88; P=0.006) compared with the TT carriers. When combined CC with CT genotype, our data showed that the genotype with at least one C allele contributed to a significant increased risk of small cell lung cancer with OR (95%CI) of2.10(1.21-3.64).Conclusion:These findings indicated that CFH rs7524776played a substantial role in the development of small cell lung cancer.