The Association between RASSF1 Gene Polymorphisms and Lung Cancer Susceptibility among People in Hubei Province of China

The relationship between Ala/Ser polymorphism in 133 codon of exon 3 region of the RASSF1 gene and genetic susceptibility of lung cancer in Hubei province Han population was investigated by a case-control study. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique was adopted to analyze the polymorphism of codon 133 of exon 3 in the RASSF1 gene of 100 pathologically diagnosed lung cancer patients, and 100 healthy controls. The relationship between different genotypes and the susceptibility of lung cancer was analyzed. Among 200 blood samples from Han people in Hubei Province, including 100 from lung cancer patients and 100 from healthy controls, the frequencies of Ala/Ala, Ala/Ser, Ser/Ser genotype of the RASSF1 in lung cancer patients were 83%, 16%, 1%, and those in healthy controls was 93%, 7%, 0% respectively, with the difference being statistically significant between two groups （P〈0.05）. The individuals with Ala/Ser genotype had higher risk of suffering from lung cancer, with an OR of 2.341, and 95% CI of 1.009-6.393 respectively. It was concluded that RASSF1Ala133Ser was a susceptible genetic factor of lung cancer. Ala/Ser genotype increased the risk of lung cancer.

Polymorphism of the DNA repair gene XPA and susceptibility to lung cancer

Objective： To study the relationship between one polymorphism in the promoter of the DNA repair gene XPA and the susceptibility to lung cancer. Methods： Genotypes were determined by the PCR-restriction fragment length polymorphism （PCR-RFLP） method in 310 histologically-confirmed lung cancer cases and 341 age and sex frequency-matched cancer-free controls. Results： The XPA A23G genotype frequencies were 27.1% （AA）, 42.9% （AG）, and 30.0% （GG） in case patients and21.1% （AA）, 5218% （AG）, and 26.1% （C-G） in control subjects. Multivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele （AG ＋ GG genotypes） had a significantly decreased risk for lung cancer （adjusted OR = 0.66; 95 % CI = 0.44- 0.98） compared with the wild-type genotype （23AA）. Stratified analysis showed that the protective effect was more evident in subjects with a family history of cancer. Conclusion： These results suggest that the XPA A23G polymorphism may have a role in lung cancer susceptibility in this study population.

Association between the DNA Repair Gene Polymorphisms and Lung Cancer in Turkish Population

Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigate the association among XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD-ERCC2 (Lys751Gln), APE1 (Asp241Glu), PARP-ADPRT (Val762Ala) DNA repair gene polymorphisms and lung cancer in Turkish population. Materials and Methods: Our patient group consists of 90 patients with lung cancer and the control group had 100 healthy individuals all of those smoking. DNA was extracted using the whole blood samples. PCR- RFLP technique was used to investigate the polymorphisms on target genes. Results: There was no significant difference in the genotype distributions of XPD Lys751Gln, XRCC1 Arg194Trp, XRCC3 Thr241Met, APE1 Asp241Glu between lung cancer patients and controls for each polymorphism (p > 0.05). However, there was a significant difference between the genotype distributions of XRCC1 Arg399Gln, and PARP Val762Ala in patients and the control group (p > 0.05). Discussion: Only the polymorphisms of XRCC1 codon 399 and PARP Val762Ala alleles are associated with the risk of lung cancer. Other genotypes were not related to lung cancer.

Cytochrome P450 2E1 RsaI/PstI and DraI Polymorphisms Are Risk Factors for Lung Cancer in Mongolian and Han Population in Inner Mongolia

Objective： To explore the relationship between cytochrome P450 2E1 （CYP2E1） RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods： CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results： The risk of lung cancer was increased in individuals with CYP2E1 （cl/cl） and CYP2E1 （DD） with OR values of 2.431 （95%CI=1.082-5.460） and 2.778 （95%CI=1.358-5.683） respectively （P0.05）. When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 （cl/c2＋c2/c2 and DD＋CC） with OR values of 0.233 （95%CI=0.088-0.615, P0.05）. In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 （c1/c1） and CYP2E1 （DD） than in the individuals with c2 and C allele （P0.05, OR=2.643 and 4.308 respectively）. There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion： CYP2E1 （c1/c1） and CYP2E1 （DD） are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 （c2﹢C） co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 （c1/c1） and CYP2E1 （DD） on the occurrence of lung cancer.

Association of Polymorphic Variants of <i>VEGF</i>and <i>KDR</i>Genes with Development and Metastasing of Non-Small Cell Lung Cancer

Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.

Relationship between ERCC1 (C8092A) single nucleotide polymorphism and efficacy/toxicity of platinum based chemotherapy in advanced non-small cell lung cancer patients

To assses the effect of single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A on the clinical outcome and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.MethodsThis article is a review of the current research on single nucleotide polymorphism and its effect on treatment outcome and toxicity of advanced stage lung cancer.Conclusion The observations indicate that more advanced studies and trials on C8092A SNPs are needed so as to assess if it could be used as a potential biomarker in the future.

Association between CHRNA3 rs1051730 Genotype and Lung Cancer Risk in Chinese Han Population:A Case-Control Study

Recent population-based genome wide association studies have revealed potential suscepti- bility loci of lung cancer at the region of chromosome 15q25.1 containing nicotinic acetylcholine re- ceptor genes. The loci increasing lung cancer risk has been widely identified in Caucasians, but whether this association also exists in Asians and whether this association is a direct role or mediated via tobacco smoking indirectly has not been fully established. We conducted a case-control study comprising of 210 histologically confirmed lung cancer cases and 200 healthy controls to examine rsl051730 genotyping, a single nucleotide polymorphism receiving much attention recently, and its influence on lung cancer risk as well as nicotine dependence in a Chinese Han population. Our results showed that the heterozy- gous C/T genotype and minor allele T conferred a significant higher risk of lung cancer than the CC homozygotes and allele C （adjusted OR=2.25, 95% CI=1.0~4.89, P=-0.040 and OR=2.18, 95% CI=1.02~4.67, P=0.045 respectively）. However, no association between the smoking habit and the CHRNA3 rs1051730 polymorphism was observed in this study. The results suggested that the rs1051730 polymorphism may modify susceptibility to lung cancer via a smoking-independent manner among Chinese Han population. Additional studies in vitro and in vivo are warranted to further elucidate the impact ofrsl051730 on lung cancer susceptibility.

The Difference of the Copy Number Variation and Loss of Heterozygosity of Human Lung Large Cell Cancer Cell Line with Different Metastatic Potential

Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by

白介素1β及白介素6基因单核苷酸多态性与食管癌放疗后肺部感染的关联

目的分析人白介素1β(interleukin 1β,IL-1β)、白介素6(interleukin 6,IL-6)基因单核苷酸多态性与食管癌放疗后肺部感染的关联,并探讨其生理病理的调控作用。方法选取新乡医学院第三附属医院2019年1月~2022年7月收治的115例食管癌患者为研究对象,根据放疗后是否出现感染分为感染组(n=28)和非感染组(n=87),检测IL-1β基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点-511C/T(rs16944)、-31C/T(rs1143627)和IL-6基因单核苷酸多态性位点IL-6-572C/G(rs1800796)、IL-6-174G/C(rs1800795)的多态性,采用Spearman相关检验分析IL-1β、IL-6基因单核苷酸多态性与食管癌放疗后肺部感染的关系,多因素Logistic回归分析影响食管癌放疗后肺部感染的相关因素。结果两组患者性别、年龄、BMI、临床分期等基线资料比较,差异无统计学意义(P>0.05);放疗时间、肿瘤长度、肿瘤位置比较差异有统计学意义(P<0.05);IL-1β基因的rs16944、rs1143627位点,IL-6基因的rs1800796、rs1800795位点的基因型分布均符合Hardy-Weinberg遗传平衡定律(P>0.05);两组IL-1β基因rs16944位点基因型频率,CC、CT、TT基因型频率,C、T等位基因频率,差异均无统计学意义(P>0.05);rs1143627位点CC、CT、TT基因型频率,C、T等位基因频率差异均有统计学意义(P<0.05);IL-6基因rs1800796位点CC、CG、GG基因型频率,C、G等位基因频率差异均有统计学意义(P<0.05),rs1800795位点CC、CG、GG基因型频率,C、G等位基因频率差异均无统计学意义(P>0.05);Spearman相关检验分析显示,IL-1βrs1143627(C/T)位点、IL-6 rs1800796(C/T)位点基因多态性与食管癌放疗后肺部感染具有显著相关性(P<0.05);多因素Logistic回归分析显示,放疗时间、肿瘤长度、肿瘤位置、IL-1βrs1143627位点、IL-6 rs1800796位点单核苷酸多态性是影响食管癌患者放疗后肺部感染的多因素(P<0.05)。结论IL-1β基因rs1143627(C/T)位点多态性及IL-6基因rs1800796(C/G)位点多态性与食管癌放疗后肺部感染有关,其中rs1143627位点T等位基因、rs1800796位点G等位基因可能是易感基因。

XPC Lys939Gln polymorphism is associated with the decreased response to platinum based chemotherapy in advanced non-small-cell lung cancer

Background Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer （NSCLC） patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939GIn gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.Methods The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C （XPC） gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.Results The distributions of XPC Lys939GIn genotypes differed significantly between the response group （complete ＋partial responses） and the non-response group （stable ＋ progressive disease; P=0.022）. The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage Ⅲ （OR, 0.074; 95% CI,0.008-0.704; P=0.023）. The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.Conclusion Polymorphisms of the XPC gene, Lys939GIn, may be a predictive marker of treatment response for advanced NSCLC patients in stage Ⅲ.

维生素D代谢途径中基因多态性与肺癌的研究进展

肺癌是当今全球恶性肿瘤中发病率和死亡率较高的一种,尽管已经研究了各种各样的方法干预肺癌的进展,但医治效果仍欠佳,加上多数患者确诊时已失去最佳手术时机,或因预防策略不足,肺癌患者收效是微弱的。维生素D(VitD)作为一种脂溶性维生素,其熟为人知的作用是调节钙磷代谢,用来治疗骨质疏松等代谢性骨病。近年来,随着医疗发展和研究的深入,发现VitD参与多种生物途径,并与癌症的发病机制息息相关。体内和体外实验已经公开了VitD发挥免疫调节和抗肿瘤的功能。本文从VitD参与肺癌的作用机制、VitD系统中基因的多态性与肺癌的关系及未来靶向治疗等方面展开综述。

ADRB1基因多态性与肺癌根治术后舒芬太尼镇痛效果的相关性研究

目的研究beta肾上腺素受体1(ADRB1)基因多态性与肺癌根治术后舒芬太尼镇痛效果的相关性。方法以2021年6月-2022年12月邯郸市中心医院胸外科收治的210例接受肺癌根治术的患者为研究对象,采用直接测序法检测患者ADRB1 rs1801252和rs1801253的基因多态性。患者入组后抽取2 mL静脉血用于基因多态性分析,记录术中麻醉药物用量及手术时间,术后收集48 h内舒芬太尼的追加镇痛药次数及使用量,采用视觉模拟评分法(VAS)评估患者疼痛感;采用医生整体评估量表(PGA)评价整体情况,记录患者恶心和呕吐情况。结果ADRB1 rs1801252 AA、AG、GG携带者人数分别为108例(51.4%),82例(39.1%)及20例(9.5%);ADRB1 rs1801253 CC、CG、GG携带者人数分别为158例(75.2%),38例(18.1%)及14例(6.7%)。ADRB1 rs1801252术后舒芬太尼镇痛效果GG携带者最好,AG携带者次之,AA携带者最差。ADRB1 rs1801253基因多态性与术后舒芬太尼镇痛效果无明显关联。结论ADRB1 rs1801252基因多态性与肺癌根治术后舒芬太尼镇痛效果相关,遗传因素是导致镇痛效果个体差异的原因之一。

两湖地区肺癌人群MICA基因分布比较分析

目的研究两湖地区中荆州和衡阳肺癌人群MICA等位基因分布差异。方法采用PCR-SSP和PCR-SBT方法对样本MICA等位基因的多态性进行检测。结果衡阳组和荆州组各检出8种MICA等位基因,其中衡阳组中未检出MICA*027,荆州组中未检出MICA*009N;荆州患者组中分布频率最高的3种等位基因是MICA*00201、MICA*019和MICA*010;衡阳患者组中分布频率最高的3种等位基因是MICA*010、MICA*00201和MICA*01201;两组之间MICA等位基因分布间存在统计学差异。衡阳组和荆州组检出的MICA等位基因型、MICA-STR等位基因分布频率和MICA-STR等位基因型均不相同,但分布总体比较无统计学差异(P>0.05)。结论两湖地区肺癌人群MICA等位基因频率分布之间存在差异。

XRCC1单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性

背景与目的DNA修复能力与肿瘤细胞对铂类药物的敏感性密切相关。本研究探讨DNA修复基因XRCC1单核苷酸多态性与非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者对顺铂(cisplatin,DDP)或卡铂(carboplatin,CBP)为主的化疗方案敏感性的关系。方法经病理学确诊的晚期NSCLC患者105例,采用DDP或CBP为主的方案化疗,2～3个周期后进行临床疗效评价。以PCR-RFLP进行XRCC1Arg194Trp和Arg399Gln多态的基因分型,比较不同基因型对化疗敏感性的影响。比值比(OR)及其95%可信区间(CI)由logistic回归模型计算。结果携带至少一个Trp等位基因者化疗有效率为43.1%,显著高于携带Arg/Arg基因型的20.3%(OR=2.97,95%CI=1.15～7.72;P<0.05)。携带XRCC1399Arg/Arg基因型者化疗有效率为41.5%,显著高于携带至少一个Gln等位基因者的21.2%(OR=2.65,95%CI=1.03～6.87;P<0.05)。这两个多态之间存在联合作用,同时携带194Arg/Trp和399Arg/Arg基因型的患者,治疗有效率为66.7%,明显高于携带其它基因型的患者(有效率20.0%～23.1%)。结论XRCC1基因多态与NSCLC患者对铂类药物化疗的敏感性相关。

肺癌易感性与NQO1、CYP1A1、mEH基因多态性的关系

[目的 ]对南京市正常人群和原发性肺癌病例进行NQO1、CYP1A1、mEH基因遗传多态性与肺癌易感性关系研究 ,探讨南京地区人群肺癌易感基因。 [方法 ]收集正常人群样本 88例 ;同时 ,应用病例 对照研究方法 ,收集南京市区原发性肺癌患者 84例 ,同时按 1∶1配对选择正常对照 84例 ,进行流行病学调查。采用PCR技术 ,对样本DNA进行NQO1、CYP1A1、mEH exon3、mEH exon4基因型的检测 ,并分析各基因型与肺癌易感性的关系。 [结果 ]南京市正常人群中 ,相关基因野生型 (wt/wt)、杂合型 (wt/vt)、突变型 (vt/vt)三种基因型的频率分布情况分别是 :NQO12 9 5 %、5 1 1%、19 3 % ;CYP1A13 5 2 %、44 3 %、2 0 5 % ;mEH exon3 2 6 1%、5 6 8%、17 0 % ;mEH exon483 0 %、15 9%、1 1%。南京市区人群NQO1、CYP1A1和mEH exon4基因多态性与肺癌易感性没有明显关系。mEH exon3基因型与肺鳞癌发生有关 ,野生型个体可降低肺鳞癌发病的风险 (OR =0 3 2 ,95 %CI :0 0 0 78～ 0 63 ) ,杂合型和突变型个体患肺鳞癌的危险性明显高于野生型个体 (OR =3 1,95 %CI :0 0 8～ 6 12 ) ;考虑吸烟因素后 ,mEH exon3基因型与吸烟者肺癌发生有关 ,野生型个体可使肺癌发病风险性降低 (OR =0 18,95 %CI :0 0 6～ 0 2 9) ,杂合型和突?

中国湖南人群GSTM1和GSTT1基因多态性与肺癌易感性关系的研究

应用病例-对照分析研究(对照组205例,肺癌病例组104例),抽提静脉血基因组DNA,采用PCR及多重PCR方法,检测谷胱甘肽转移酶GSTM1和GSTT1单独及联合缺失基因型的遗传多态性在中国湖南人群中肺癌患者和正常人群体中的分布,探讨这些多态性基因型与肺癌易感性的关系.结果显示GSTM1-/-基因型在湖南地区居民肺癌群体和正常对照人群中的频率分别为62.5%和46.3%(P<0.05);肺癌患者组GSTT1-/-基因型的频率(66.3%)显著高于正常对照组(42.4%)(P<0.05).GSTM1-/-和GSTT1-/-联合基因型在肺癌组和正常对照组中的频率分别为41.3%和22.4%(P<0.05).SPSS11.5软件统计学分析表明,这些基因型在肺癌患者组和正常对照组人群中的发生频率具有显著性差异.由此可知GSTM1基因缺失和GSTT1基因缺失分别与肺癌的易感性相关;GSTM1和GSTT1基因联合缺失与肺癌的发生和发展呈现显著正相关.

南京市人群DNA修复基因XRCC1多态性与肺癌易感性的关系

[目的]研究碱基切除修复基因XRCC1多态性与南京市人群肺癌易感性的关系。[方法]采用配对病例_对照研究 ,收集南京籍原发性肺癌患者104例为病例组 ,同时按1:1配对选择非肿瘤、非呼吸道疾病患者104例为对照组 ,并进行流行病学调查。应用PCR_RFLP方法分析了病例组和对照组的XRCC1基因Arg194Trp和Arg399Gln两个位点的多态性 ,比较不同基因型与肺癌易感性的关系 ,以及基因多态性与吸烟之间对肺癌易感性的交互作用。[结果]携带399Gln等位基因的个体其肺癌危险性增高 (OR=1.790 ,95 %CI=1.033～3.103 ,P=0.038) ,且主要增加患鳞癌的危险 (OR=2.426 ,95 %CI=1.123～5.237,P=0.023);并与吸烟指数≥20的有一定的协同作用 (OR=2.536 ,95 %CI=1.043～6.165)。Arg194Trp与肺癌危险性之间未见显著性相关 (OR=1.040 ,95%CI=0.600～1.805)。[结论]碱基切除修复基因XRCC1的多态性可能会对肺癌易感性产生影响 。

髓过氧化物酶基因多态性与肺癌遗传易感性的研究

背景与目的:髓过氧化物酶(myeloperoxidase,MPO)基因启动子区域-463bp处存在G/A多态位点,国外研究表明此位点与肺癌遗传易感性有关,但中国人MPO基因型与肺癌易感性关系尚未见报道,本研究拟对此问题作一探讨。方法:采用病例-对照分子流行病学方法,以PCR-RFLP技术检测98例原发性肺癌和112名健康对照MPO基因型,通过比较不同基因型者的比值比(oddsratio,OR)及其95%可信区间(confidenceinterval,CI)分析基因多态性与中国人肺癌易感性的关系。结果:正常人群G/G、G/A、A/A基因型频率分别为47.3%、42.9%和9.8%,肺癌病例组分别为63.3%、33.7%和3.0%,杂合子G/A在两组人群中分布无显著性差异(P>0.05),但病例组A/A基因型频率显著低于对照组(P<0.025)。携带至少一个等位基因A者患肺癌的风险是基因型为G/G者的52.0%(95%CI0.29～0.93)。在吸烟人群中,等位基因A对肺癌易感性的保护作用有显著性意义(OR=0.41,P<0.025),而在非吸烟人群,这种保护作用无显著性意义(P>0.25)。结论:本研究人群MPO基因多态与肺癌遗传易感性相关,等位基因A对吸烟人群的肺癌易感性有保护作用。