| Objectives This study aims to examine the association of CFI genetic variants with the risk of developing non small cell lung cancer(NSCLC) in Chinese population.Methods This study consisted of 470 patients with NSCLC and 470 cancer-free controls who were genetically unrelated Chinese populations. The patients were consecutively recruited between March 2008 and December 2012 at the Tangshan Gongren Hospital. NSCLC cases were included only if they had been originally diagnosed as adenocarcinoma, squamous cell carcinoma, or large cell carcinoma based on the description of the World Health Organization(WHO). All histological and cytological slides were determined by two experienced pathologists. All patients were previously untreated by radiotherapy and chemotherapy. There were no age, gender, stage, or histology restrictions. Patients with a previous malignancy or metastasized cancer from other organs were excluded. The controls were randomly selected from a cancer-free population from a community conducted in the same region during the same period when patients were recruited. The selection criteria for the controls included no prior history of malignancy, and control subjects were frequency matched to the patients by age(±5 years) and gender. Statistical analyses were performed using the SPSS 16.0 statistical software package. The χ2 test was used to compare the distributions of genotypes between cases and controls. Odds ratios(OR) and 95% confidence intervals(CI) were used to evaluate the association of CFI genetic variants with the risk of NSCLC using unconditional logistic regression adjusted by age, sex, and smoking status. We used Haploview 4.2 program with an r2 threshold of 0.80 and minor allele frequency(MAF) greater than1%. Totally, 13 tag single nucleotide polymorphisms(tag SNPs) of CFI were selected by Haploview software using the Hap Map database. Genotyping was performed using i PLEX Gold Genotyping Assay and Sequenom Mass ARRAY.Results Totally, 13 tag SNPs of CFI(rs11726949, rs13104777, rs6822976, rs74817407, rs4698784, rs4541508, rs7356506, rs12512308, rs4626205, rs4288008, rs10029485, rs4698788, rs7671905) were selected by Haploview software using the Hap Map database. We found that CFI rs6822976 and rs7671905 polymorphism were related to the risk of non small cell lung cancer. Our results showed that individuals with rs6822976 GG genotype had a significant decreased risk of NSCLC(OR=0.64; 95 % CI=0.42~0.98) when compared with rs6822976 AA genotype carriers. We also found that rs7671905 TT genotype exhibited a significant decreased risk of NSCLC compared with CC genotype with OR(95 % CI) of 0.55(0.33~0.91). There was no significant association between other selected SNPs and the risk of NSCLC. When stratified by smoking status, the decreased risk of NSCLC was observed to be associated with the genotype with at least one rs6822976 G allele among nonsmokers(OR=0.66; 95 % CI=0.47~0.93), but not among smokers(OR=1.01; 95 % CI=0.67~1.53). For CFI rs7671905 polymorphism, the individuals with at least one T allele have a decreased risk of NSCLC with OR(95 % CI) of 0.71(0.51~0.99), but not among smokers(OR=0.93; 95%CI=0.61~1.41). When stratified by age, we found that rs7671905 TT genotype has contributed to the decreased risk of NSCLC among older subjects with OR(95 % CI) of 0.46(0.23~0.95), but not among younger subjects with OR(95 % CI) of 0.64(0.31~1.34)(Pinteraction=0.03). After stratifying by sex, our study showed that rs7671905 TT genotype was related to the risk of NSCLC among males(OR=0.53; 95 % CI=0.29~0.98), but not among females(OR=0.62; 95 % CI=0.25~1.57)(Pinteraction=0.03). CFI genetic variants played an important role in the development of NSCLC in Chinese population.Conclusions These findings indicated that CFI rs6822976 and rs7671905 played a substantial role in the development of non small cell lung cancer. |
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