关键词: 非小细胞肺癌（NSCLC）, 瘦素（LEP）, 单核苷酸多态性（SNP）, 易感性

Abstract: ObjectiveTo investigate the leptin （LEP） level and the association of its single nucleotide polymorphisms （SNPs） with susceptibility to nonsmall cell lung cancer （NSCLC）. MethodsFrom January 2014 to December 2016， peripheral blood samples were collected from 142 cases of NSCLC patients following pathological diagnosis. Using the Sequenom MassARRAY system via matrix assisted laser desorption ionization timeofflight mass spectrometry （MALDITOFMS）， LEP polymorphism of rs4731423， rs10487506， rs2167270， rs17151919， rs1800564 and rs11761556 were genotyped. The peripheral blood samples of 176 healthy controls were selected for comparison. The distribution of SNPs genotypes and alleles in NSCLC patients and healthy controls were compared. The odds ratio （OR） and its 95％ confidence interval （95％CI） were calculated to evaluate the relationship between SNPs and NSCLC susceptibility. The serum LEP levels in patients with NSCLC were measured by radioimmunoassay. The relationship of serum LEP level with clinicopathological parameters， including gender， age， pathological type， tumor size， TNM stage and lymph node metastasis and LEP SNPs were analyzed. 
ResultsThe distribution of rs4731423， rs10487506， rs2167270 and rs11761556 genotypes in 142 NSCLC patients and 176 healthy controls was in accordance with HardyWeinberg balance. There was no significant difference in genotype and allele distribution of rs10487506 and rs11761556 between NSCLC group and control group （P＞0.05）. Regarding rs4731423 distribution， the frequency of GG genotype in NSCLC group was 317％ （45／142）， and the allele frequency of G was 514％ （146／284）， higher than 18.8％ （33／176） and 372％ （131／352） in control group （P＜0.05）. As for the rs2167270 distribution， the frequency of AA genotype in NSCLC group was 155％ （22／142）， higher than 74％ （13／176） of control group， and the difference was statistically significant （P＜0.05）. However， there was no significant difference in the frequency of allele distribution between both groups in term of rs2167270 （P＞0.05）. LEP rs10487506， rs2167270 and rs11761556 were not associated with the risk of NSCLC （P＞0.05）. For rs4731423， as compared to AA genotype， GG and AG+GG genotypes increased the risk of NSCLC to 2594 and 1961 folds （P＜0.05）， but AG did not change the risk of NSCLC （P＞0.05）. When taking A allele as the reference， risk of G allele for NSCLC increased to 1785 folds （P＜0.05）. The level of LEP was independent of gender， age， pathological type， lymph node metastasis， rs10487506， rs2167270 and rs11761556， but related with tumor size， TNM stage and rs4731423 （P＜0.05）. The serum LEP levels of AG， GG and AG+GG were higher than AA， and the difference was statistically significant （P＜0.05）. ConclusionLEP rs4731423 was related to NSCLC susceptibility and LEP level. The risk of NSCLC and LEP level increased for G allele carriers， presenting a certain value in the screening of NSCLC susceptible population.

Key words: Nonsmall cell lung cancer（NSCLC）, Leptin（LEP）, Single nucleotide polymorphism（SNP）, Susceptibility