基质金属蛋白酶-2单核苷酸多态性与非小细胞肺癌的关系

目的:研究基质金属蛋白酶-2(MMP-2)单核苷酸多态性与非小细胞肺癌(NSCLC)的关系.方法:以聚合酶链反应和DNA测序等基因多态性分析方法,分别检测非小细胞肺癌患者和正常对照MMP-2-1306T/C基因型,比较不同基因型与肺癌的关系.结果:与MMP-2-1306TT或MMP-2-1306CT基因型携带者比较,MMP-2-1306CC基因型携带者的非小细胞肺癌易感性较高.结论:MMP-2基因的多态性可能与非小细胞肺癌的遗传易感性有关.     

基质金属蛋白酶-2单核苷酸多态性与非小细胞肺癌的关系

目的:研究基质金属蛋白酶-2(MMP-2)单核苷酸多态性与非小细胞肺癌(NSCLC)的关系。方法:以聚合酶链反应和DNA测序等基因多态性分析方法,分别检测非小细胞肺癌患者和正常对照MMP-2-1306T/C基因型,比较不同基因型与肺癌的关系。结果:与MMP-2-1306TT或MMP-2-1306CT基因型携带者比较,MMP-2-1306CC基因型携带者的非小细胞肺癌易感性较高。结论:MMP-2基因的多态性可能与非小细胞肺癌的遗传易感性有关。     

VEGF基因-460T/C单核苷酸多态性与河北地区汉族人群肺癌发病风险相关性分析

目的:研究血管内皮生长因子(VEGF)基因启动子区-460T/C单核苷酸多态性(SNP)与河北地区汉族人群肺癌发病风险的关系。方法:采用基于医院的病例-对照研究方法,采集200例肺癌患者和204名健康对照的静脉血,同时记录其病史和个人相关资料。以蛋白酶K消化-饱和氯化钠盐析法提取外周血白细胞DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和引物介导的限制性聚合酶链反应(PIRA-PCR)方法检测VEGF-460T/C多态性位点的基因型。结果:肺癌组VEGF-460C/T SNP C等位基因频率(27.5%)明显高于对照组(20.1%),两组比较差异有统计学意义,χ2=6.109,P=0.013。肺癌组与对照组的T/T、T/C+C/C基因型频率分别为52.2%、47.5%和63.2%、36.7%,差异有统计学意义,χ2=4.445,P=0.029。与T/T基因型相比,携带C等位基因(T/C+C/C)的基因型可显著增加肺癌的发病风险;与T/T基因型相比,携带C等位基因(T/C+C/C)的基因型可显著增加不吸烟人群的发病风险。与T/T基因型相比,携带C等位基因的基因型(T/C+C/C),明显增加肺鳞状细胞癌及小细胞癌发病风险。结论:VEGF-460T/C SNP可能与肺癌发病风险相关。     

DNA修复基因XPD 312 Asn和751Lys多态性与非吸烟女性肺癌的关系

目的 着色性干皮病互补基因D(xeroderma pigmentosum group D,XPD)是一种重要的DNA损伤修复基因,其常见的多态是位于751密码子的A→C颠换和312密码子G→A转换。本研究旨在探讨XPD基因751位点和312位点单核苷酸多态性与非吸烟女性肺癌易感性的关系。方法 采用病例-对照研究方法,纳入非吸烟女性肺癌患者222人和对照222人。以聚合酶链反应-限制性片段长度多态性方法分析XPD基因Lys751Gln和Asp312Asn多态基因型。结果 携带至少1个751Gln等位基因者和携带至少1个312Asn等位基因者患肺癌的风险均显著增高,调整OR分别为3.36(95%CI为2.29-4.90)和1.83(95%CI为1.16-2.91)。结论 XPD基因Lys751Gln和Asp312Asn多态是非吸烟女性肺癌的遗传易感因素。     

XPD基因多态性与非吸烟女性肺癌易感性的关系

背景与目的 着色性干皮病互补基因D（xeroderma pigmentosum group D，XPD）是一种重要的DNA损伤修复基因，其常见的多态是位于751密码子的A→C多态。本研究旨在探讨XPD基因751位点单核苷酸多态性与非吸烟女性肺癌易感性的关系，并探讨油烟暴露与基因多态性交互作用对肺癌风险的影响。方法 采用病例-对照研究方法，纳入非吸烟女性肺癌患者105人和对照105人。以聚合酶链反应-限制性片段长度多态性方法分析XPD基因Lys751Gln多态基因型。结果 携带至少1个751Gln等位基因者患肺癌的风险显著增高，调整OR为2．80（95％CI为1．21～6．48）。携带等位基因751Gln又有油烟暴露的个体患肺癌的风险较两个危险因素单独作用时更高，校正OR为6．85（95％CI为1．69～27．67，P=0．007）。结论 XPD基因Lys751Gln多态是非吸烟女性肺癌的遗传易感因素。携带XPD751Gln等位基因又有油烟暴露的非吸烟女性患肺癌的风险明显增高。     

β1-509C/T基因多态性与中国人群NSCLC遗传易感相关性的研究

目的:探讨转化生长因子β1基因(TGF-β1)-509C/T位点多态性与中国人群非小细胞肺癌(non-small cell lungcancer,NSCLC)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性PCR-RFLP方法检测210例NSCLC患者和208例健康对照者的TGF-β1-509C/T基因型分布,并分析两组之间的差异。结果:TGF-β1-509CT+TT基因型相对于CC基因型是NSCLC发生的独立危险因素(P=0.007,OR=2.297,95%CI:1.250～4.219);携带T等位基因者患NSCLC的风险是携带C等位基因者的1.617倍(P=0.001,95%CI:1.210～2.161);重度吸烟者相对于不吸烟和轻度吸烟者是NSCLC发生的独立危险因素(P=0.021,OR=1.783,95%CI:1.089～2.918)。结论:TGF-β1-509C/T位点多态性在中国人群中与NSCLC遗传易感性相关,可作为NSCLC发病风险评估的筛选指标。     

ATM基因单核苷酸多态性与非小细胞肺癌易感性的研究

背景与目的：毛细血管扩张性共济失调症突变基因（ataxia-telangiectasia mutated,ATM）是导致毛细血管扩张性共济失调症发生的致病基因,与肿瘤的发生密切相关。ATM基因是一个重要的信号传感器,可以通过将目标蛋白磷酸化从而修复DNA双链的断裂。本研究旨在探讨ATM基因（IVS62＋60G〉A）单核苷酸多态性与非小细胞肺癌（non-small cell lung cancer,NSCLC）发生的相关性。方法：收集2004年6月-2005年12月期间浙江省肿瘤医院就诊的264例NSCLC患者标本以及264例健康体检者作为正常对照组,分离外周血白细胞DNA。ATM基因单核苷酸多态性分型检测采用Taqman探针基因分型技术,应用Logistic回归统计分析ATM单核苷酸多态性与NSCLC发生相关性。结果：在NSCLC病例组中,A/A基因型占32.6%,A/G基因型占52.6%,G/G基因型占14.8%。而正常对照组中相应的数值分别为26.0%、53.0%和21.0%。在NSCLC病例组中,携带基因型G/G的比率明显低于正常对照组（14.8%vs21.0%,P〈0.08）。携带有G/G基因型者肺癌发生的风险明显低于携带有A/A基因型者（OR=0.561,95%CI为0.334～0.942,P=0.029）。结论：ATM单核苷酸多态性（IVS62＋60G〉A）与NSCLC发生密切相关,G等位基因的纯合状态可能是发生NSCLC的保护性因素。     

XRCC1多态性与非吸烟女性肺腺癌易感性的关系

背景与目的XRCC1是一种DNA损伤修复基因，其单核苷酸多态性异常是导致DNA修复能力个体差异的重要原因，可能导致个体患肺癌的危险升高。本研究的目的是探讨XRCC1单核苷酸多态性与非吸烟女性肺腺癌易感性的关系。方法采用以医院患者为基础的病例对照研究方法，研究对象包括非吸烟女性肺腺癌患者126例和同期其它肺部疾病对照126例。以聚合酶链反应一限制性片段长度多态性方法分析XRCC1基因Arg399Gln多态性，比较不同基因型与非吸烟女性肺腺癌的关系，并探讨油烟暴露与基因多态交互作用对患癌风险的影响。结果与携带399Arg／Arg基因型者比较，携带399Gln／Gln基因型者患肺腺癌的风险是其8．695倍（95％CI为3．343～22．614）。携带等位基因399Gln又有油烟暴露的个体患肺腺癌的风险明显增高，校正的比值比为5．21（95％CI为1．85～14．70，P〈0．001）。结论XRCC1基因Arg399 Gln多态性可能是非吸烟女性肺腺癌的遗传易感因素。     

β1-5090／T基因多态性与中国人群NSOLC遗传易感相关性的研究

目的：探讨转化生长因子β1基因（TGF-β1）-509C／T位点多态性与中国人群非小细胞肺癌（non-small cell lung cancer,NSCLC）遗传易感性的关系。方法：采用聚合酶链反应-限制性片段长度多态性PCR—RFLP方法检测210例NSCLC患者和208例健康对照者的TGF-β1—509C／T基因型分布,并分析两组之间的差异。结果：TGF—β1—509CT＋TT基因型相对于CC基N型是NSCLC发生的独立危险因素（P=0．007,OR=2．297,95％CI：1．250-4．219）;携带T等位基因者患NSCLC的风险是携带C等位基因者的1．617倍（P=0．001,95％CI：1．210～2．161）;重度吸烟者相对于不吸烟和轻度吸烟者是NSCLC发生的独立危险因素（P=0．021,OR=1．783,95％CI：1．089～2．918）。结论：TGF-β1—509C／T位点多态性在中国人群中与NSCLC遗传易感性相关,可作为NSCLC发病风险评估的筛选指标。     

基质金属蛋白酶1基因多态性与非小细胞肺癌的关系

目的研究基质金属蛋白酶1(metal matrix proteinase-1,MMP-1)启动子区-1607bp处1G或2G单核苷酸多态性(single nucleotide polymorphism,SNP)与中国北方人非小细胞肺癌(non-small cell lung carcinoma,NSCLC)遗传易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)方法分析159名NSCLC患者和350名健康对照的MMP-1启动子区SNP的基因型。结果NSCLC患者组和健康对照组的2G/2G、1G/2G、1G/1G基因型频率分别为54.1%、33.9%、12.0%和55.4%、30.0%、14.6%,两组间分布无显著性差异(χ2=1.13,P=0.57);病例组和对照组的2G和1G等位基因频率分别为71.1%、28.9%和70.4%、29.6%,两组间亦无显著性差异(χ2=0.04,P=0.84);根据吸烟状况及病理类型进行分层分析,未发现该基因多态性对NSCLC易感性的影响;在有或无淋巴转移患者组中MMP-1等位基因及基因型频率相似。结论MMP-1启动子区SNP与中国北方人的NSCLC发病易感性及淋巴转移无明显关系。     

云南省汉族人群TNF-α基因多态性与非小细胞肺癌发生、发展的相关性

背景与目的：肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）不仅是一种重要的炎症因子,还与肿瘤的发生、发展密切相关。探讨TNF-α基因多态性与云南省汉族人群非小细胞肺癌（non-small cell lung cancer,NSCLC）发生、发展的相关性。方法：选取云南省425例汉族人群NSCLC病例和438名健康体检者,采用TaqMan探针基因分型法对TNF-α基因启动子区域5个单核苷酸多态性（single nucleotide polymorphism,SNP）位点rs1799964（-1031T>C）、rs1800630（-863C>A）、rs1799724（-857C>T）、rs1800629（-308G>A）和rs361525（-238G>A）进行基因分型并分析其等位基因、基因型及所构建的单倍型在NSCLC病例及健康对照者中的频率差异。结果：TNF-α基因启动子5个SNP位点的等位基因和基因型频率在NSCLC病例组和对照组间差异无统计学意义（P＞0.05）。病例分层分析发现,rs1799724（C>T）的T等位基因在腺癌组中的频率显著高于对照组（P=0.010,OR=1.56,95% CI：1.11~2.19）,在显性模式下携带T等位基因的个体（TT+CT）患肺腺癌的风险显著升高（P=0.007,OR=1.66,95% CI：1.15~2.42）。rs1800630（C>A）的A等位基因在腺鳞癌及其他类型肺癌组中的频率显著高于对照组,差异有统计学意义（P=0.013,OR=2.15,95% CI：1.16~3.96）。单倍型分析结果显示,单倍型rs1799724T-rs1800629G在腺癌组中的频率显著高于对照组（P=0.048,OR=1.42,95% CI：1.00~2.01）。结论：位于TNF-α基因启动子区域的SNP位点rs1799724（C>T）等位基因T和基因型TT可能是云南省汉族人群NSCLC中腺癌发生的风险性因素。SNP位点rs1800630（C>A）等位基因A可能是云南省汉族人群NSCLC中腺鳞癌及其他类型肺癌发生的风险性因素。     

Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population

Myeloperoxidase (MPO), an enzyme derived from neutrophils, metabolically activates a wide range of carcinogens, whereas glutathione S-transferase M1 (GSTM1) detoxifies various electrophilic metabolites. A -463G-->A polymorphism in the promoter region of the MPO gene diminishes the expression of MPO and has been consistently shown to be associated with reduced risk of lung cancer in different ethnic populations. In our study, we have assessed the role of this polymorphism in lung cancer risk in a Chinese population. Genotypes of MPO and GSTM1 were determined by PCR-SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency-matched controls. The allele frequency for MPO -463A was found to be 0.155 in controls and 0.114 in cases. Subjects with the MPO -463GG genotype were at an increased risk of squamous cell carcinoma (SCC) of the lung compared to those having at least one -463A variant allele (adjusted odds ratio [OR] 2.35; 95% confidence interval [CI] 1.40-3.94). Stratified analysis suggested an interaction between heavy smoking (> or =26 pack-years) and the MPO-463GG genotype. The adjusted OR of lung SCC for those having MPO-463GG genotype and smoked > or =26 pack-years was 20.50 (95% CI 5.58-75.33) compared to 6.22 (95% CI 1.72-22.47) for those smoked > or =26 pack-years but having at least one variant A allele (p = 0.023, test for homogeneity). This effect of the MPO polymorphism was not observed in lung adenocarcinoma. GSTM1 deletion was quite common in both controls (49.4%) and cases (50.3%) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism. Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer.     

Clinical Significance of the NQO1 C609T Polymorphism in Non Small Cell Lung Adenocarcinoma Patients

Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is part of the antioxidant defence system involved in detoxification. This study aimed to analyze the influence of NQO1 (C609T) genetic polymorphism in non small cell lung cancer (NSCLC)as a putative risk factor. Materials and Methods: Present study included 100 cases of NSCLC (adenocarcinoma) patients and 100 age and sex matched healthy controls. NQO1 (C609T) genotyping was performed by allele specific PCR for assessment of putative associations with clinical outcome and genotypes of. The association of the polymorphism with the survival of NSCLC patients’ was analyzed by Kaplan–Meier method. Results: In Indian NSCLC (adenocarcinoma) patients increased risk of developing NSCLC was found to be associated with NQO1 609TT genotype [OR 3.68(0.90-14.98), RR 2.04(0.78-5.31)] for CT [OR 2.91(1.58- 5.34), RR 1.74(1.23-2.44) p= 0.0005 for CT], for CT+TT [ OR 3.26(1.82-5.82), RR 1.87(1.34-2.61) p<0.0001 for CT+TT]. A significant difference (p=0.0009) was observed in genotype distribution among cases and healthy controls. Patients with CT+TT genotype exhibited a significant poor overall survival compared with patients displaying homozygous CC genotype (p=0.03) and when survival independently compared with CC, TT and CT genotype was also found to be significantly associated (p=0.02). Overall median survival times were CT 6.0 months, TT 8.2 months, and CT + TT (6.4 months)]. Conclusions: The present study revealed that NQO1 CT, TT and CT+TT genotypes may be associated with clinical outcome and risk of developing NSCLC in the Indian population.     

The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer

STUDY OBJECTIVES: Interleukin-10 (IL-10) is mainly an anti-inflammatory cytokine produced by a number of cells including normal and neoplastic cells and has been implicated in autoimmunity, transplantation tolerance and tumorigenesis. Inter-individual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether polymorphisms in the IL-10 gene promoter were involved in predisposing an individual to non-small cell lung cancer (NSCLC). PATIENTS: A total of 154 patients with non-small cell lung cancer were recruited into this study, together with 205 age- and gender-matched healthy smokers acting as control subjects. MEASUREMENTS: Polymorphisms of sites within the promoter region of IL-10 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism technique on genomic DNA isolated from peripheral lymphocytes. The validity of this technique was proven by direct sequencing of polymerase chain reaction products. Statistical analyses were conducted to explore the contribution of polymorphism of IL-10 promoter to the susceptibility to NSCLC. RESULTS: The distribution frequencies of genotypes of IL-10-1082, -819 and -592 were significantly different between NSCLC patients and controls. Pearson chi2 analysis showed that the frequency for IL-10-1082 G allele, IL-10-819C allele and IL-10-592C allele was independently higher in NSCLC patient group than that in the control group. Higher odds ratios (ORs) for NSCLC were seen for individuals with G allele of IL-10-1082 [OR=5.26, 95% CI 2.65-10.4, p<0.0001], C allele of IL-10-819 [OR=1.57, 95% CI 1.15-2.16, p=0.005], C allele of IL-10-592 [OR=1.59, 95% CI 1.15-2.19, p=0.005]. CONCLUSION: The polymorphisms of IL-10 genes were significantly associated with the occurrence of NSCLC.