瘦素水平及其基因多态性与非小细胞肺癌易感性的关系分析

The association of leptin level and gene polymorphism with susceptibility to non-small cell lung cancers

目的探讨瘦素(LEP)水平及其单核苷酸多态性(SNPs)与非小细胞肺癌(NSCLC)易感性的关系。方法收集2014年1月至2016年12月经病理确诊的142例NSCLC患者的外周血,在Sequenom Mass ARRAY系统上利用基质辅助激光解吸电离飞行时间质谱法(MALDI-TOFMS)进行LEP多态性位点rs4731423、rs10487506、rs2167270、rs17151919、rs1800564和rs11761556的基因分型,同时收集176例健康体检者的外周血进行对比。采用Hardy-Weinberg平衡分析以上6个SNPs位点的遗传平衡情况,比较两组以上SNPs基因型和等位基因的分布差异并计算比值比(OR)及其95%置信区间(95%CI)来评价NSCLC易感性;采用放射免疫分析法检测142例NSCLC患者的血清LEP水平,并分析与NSCLC临床病理学特征(性别、年龄、病理类型、肿瘤大小、TNM分期及淋巴结转移)和LEP SNPs的关系。结果 142例NSCLC患者及176例健康体检者rs4731423、rs10487506、rs2167270和rs11761556基因型的分布符合Hardy-Weinberg平衡。NSCLC组与对照组rs10487506、rs11761556基因型及等位基因分布的差异无统计学意义(P>0.05);rs4731423分布上,NSCLC组GG基因型频率为31.7%(45/142),G等位基因频率为51.4%(146/284),均高于对照组的18.8%(33/176)和37.2%(131/352),差异有统计学意义(P<0.05);rs2167270分布上,NSCLC组AA基因型频率为15.5%(22/142),高于对照组的7.4%(13/176),差异有统计学意义(P<0.05),但两组等位基因分布频率的差异无统计学意义(P>0.05)。LEP rs10487506、rs2167270和rs11761556与NSCLC的发病风险均无关(P>0.05);rs4731423分布上,以AA基因型为参照,GG基因型发生NSCLC的风险升高至2.594倍,AG+GG基因型则升高至1.961倍(P<0.05),而AG基因型发生NSCLC的风险未改变(P>0.05);以A等位基因为参照,G等位基因发生NSCLC的风险升高至1.785倍(P<0.05)。血清LEP水平与性别、年龄、病理类型、淋巴结转移、rs10487506、rs2167270及rs11761556均无关,但与肿瘤大小、TNM分期有关(P<0.05);血清LEP水平与rs4731423有关,其中AG、GG和AG+GG基因型的血清LEP水平均高于AA型,差异有统计学意义(P<0.05)。结论 LEP rs4731423与NSCLC易感性及LEP水平有关,其中携带G等位基因的NSCLC发生风险升高且LEP水平升高,在NSCLC易感人群筛查中有一定价值。

Objective To investigate the leptin（LEP） level and the association of its single nucleotide polymorphisms（SNPs） with susceptibility to non-small cell lung cancer（NSCLC）.Methods From January 2014 to December 2016,peripheral blood samples were collected from 142 cases of NSCLC patients following pathological diagnosis.Using the Sequenom Mass ARRAY 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.Results The 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 was51.4%（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）.Conclusion LEP 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.