江苏淮安人群食管癌发病危险与易感基因多态性

目的探讨江苏淮安食管癌高发地区人群食管癌相关代谢酶基因与DNA修复酶基因的分布特征,为食管癌的病因学研究及该地区人群食管癌一级预防提供依据.方法通过1:1配对病例-对照研究,应用PCR-RFLP技术分析106对原发性食管癌患者及其对照样本代谢酶基因CYP1A1、CPY2E1、GSTM1、GSTT1和DNA修复酶基因XPD、XRCC1的多态性.结果CYP1A1、CYP2E1、GSTM1、GSTT1基因多态性与淮安人群食管癌易感性升高之间没有明显相关性.XPD基因多态性和XRCC1基因194位点多态性未见与食管癌易感性相关;XRCC1基因399位点的多态性与食管癌易感性相关,携带突变纯合子Gln/Gln的个体患食管癌的易感性显著高于对照人群(OR=3.447,95%CI=1.078～11.026,P=0.029).代谢酶基因与DNA修复酶基因在食管癌发生中交互作用的分析发现,CYP2E1基因突变基因型与GSTT1基因缺失型同时存在的个体,其患食管癌的危险性下降(OR=0.305,95%CI=0.116～0.802);同时,XRCC1基因194位点与399位点的突变基因型也可使食管癌发生的危险性有所降低(OR=0.329,95%CI=0.121～0.897).结论XRCC1基因399位点多态性与淮安人群食管癌易感性有关;相关基因之间存在一定的交互作用,这种交互作用对基因功能的影响及其在食管癌发生中的意义值得深入探讨.     

CYP1A1 GSTM1基因多态性和吸烟与肺癌易感性关系的病例对照研究

目的:探讨天津市居民致癌物代谢酶CYP1A1和GSTM1基因多态性对肺癌易感性的影响。方法:利用限制性片断长度多态性-聚合酶链反应(RFLP-PCR)方法检测原发性肺癌患者和健康对照者细胞色素P450酶基因CYP1A1Msp位点和谷胱甘肽硫转移酶基因GSTM1的多态性情况。结果:肺癌组与对照组之间CYP1A1和GSTM1基因型分布差异均存在统计学显著意义(P<0.05)。携带CYP1A1变异基因型或GSTM1阴性基因型的个体患肺癌的危险性增高,比值比(OR)分别达到2.44(1.04～5.81)和1.84(1.03～3.29)。多因素分析结果显示具有CYP1A1变异基因型、GSTM1阴性基因型的吸烟个体患肺癌的风险较大。结论:CYP1A1Msp位点变异基因型和GSTM1阴性基因型可能是肺癌的易感因素,吸烟与肺癌易感基因之间具有协同作用。     

CYP1A1和GSTM1基因多态性与内蒙古人群肺癌易感性的关系

背景与目的 肺癌是严重危害人类健康的恶性肿瘤之一，其发病与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4501A1（CYP1A1）基因多态性和谷胱甘肽硫转移酶M1（GSTM1）基因多态性与内蒙古人群肺癌易感性的关系。方法 用PCR-RFLP技术分析了原发性肺癌组和住院对照组（各163例）的CYP1A1、GSTM1基因的多态性、基因型分布频率和交互作用。结果 CYP1A1突变型和GSTM1基因缺陷型EGSTM1（-）]频率分布分别为36．8％、65．0％（病例组）和19．0％、48．9％（对照组），二者经χ^2检验差异有显著性（χ^2=12．82，P=0．000；χ^2=9．78，P=0．002）。CYP1A1突变型患肺癌的风险显著增加（OR=2．48，95％CI为1．51～4．08）。GSTM1（-）者患肺癌的风险也显著增加（OR=2．03，95％CI为1．30～3．17）。基因突变的协同分析发现CYP1A1突变型／GSTM1（-）在肺癌组和对照组中的分布频率分别为28．8％和8．0％，二者经χ^2检验有显著性差异（χ^2=23．883，P=0．000）。CYP1A1突变型／GSTM1（-）患肺癌的风险显著增加（OR=4．90，95％CI为2．50～9．83）。无论是在肺癌组还是在对照组，CYP1A1突变型／GSTM1（-）和CYP1A1非突变型／GSTM1（-）在性别间分布频率的差异均无显著性（肺癌组χ^2=0．797，P=0．372；对照组χ^2=0．670，P=0．761）。吸烟与肺癌易感性的统计学分析，结果显示吸烟与肺癌易感性有关（χ^2=14．197，P=0．000），吸烟者患肺癌的风险显著增加（OR=2．33，95％CI为1.50～3．62）。CYP1A1突变型与吸烟关系的协同分析发现，携带CYP1A1突变型基因的吸烟者较携带CYP1A1突变型基因不吸烟者易患肺癌（OR=4．44，95％CI为2．40～8．32，χ^2=23．843，P=0．000）。GSTM1（-）与吸烟关系的协同分析中也发现，携带GSTM1（-）的吸烟者患肺癌的风险显著增加（OR=7．32，95％CI为3．39～15．50，χ^2=36．708，P=0．000）。结论 CYP1A1突变型和GSTM1（-）是内蒙古地区肺癌的易患因素，二者对肺癌的发生有协同作用，吸烟与肺癌的易感性也有关，CYP1A1突变型、GSTM1（-）与吸烟在肺癌的发生上也有相互促进作用。     

EGFR基因rs763317多态性与胃癌遗传易感的相关性研究

目的:探讨EGFR基因第一内舍子区rs763317位点单核苷酸多态性(SNP)与江西地区汉族人群胃癌遗传易感性的相关性.方法:应用MassARRAY(R)SNP分型技术检测138例胃癌患者和170名正常对照EGFR基因多态位点rs763317的基因型.用χ2检验统计分析病例组和对照组基因型和等位基因的频率;采用非条件Logistic回归分析,计算比数比(OR)和95%CI,评价多态性位点与胃癌遗传易感性的相关性.结果:EGFRrs763317多态位点AA、AG和GG基因型在胃癌人群中的分布频率为5.8%、52.2%和42.0%,与对照组(2.4%,31.8%和65.9%)相比差异有统计学意义,P≤0.001.与rs763317 GG基因型相比,携带AA或AG基因型的个体能显著增加患胃癌的发病危险(OR=3.909,95%CI:1.108～13.786;OR=2.540,95%CI:1.565～4.123).等位基因A在胃癌患者的分布频率显著高于正常对照组(OR=3.277,95%CI:1.103～9.738).结论:首次发现EGFR基因第一内含子区rs763317位点多态性与江西地区汉族人群胃癌的遗传易感性相关.     

CYP1A1和GSTMI基因多态性及其对个体肺癌易感性的联合效应:meta分析

背景与目的 谷胱甘肽转移酶M1(glutathione S-transferase MI,GSTM1)和细胞色素P4501A1(cytochrome P450A1,CYP1A1)均存在基因多态性,并且对肺癌发病风险有一定的影响,两者联合作用对肺癌发病风险的影响尚无确切定论.本研究旨在探讨CYPIAI和GSTMI基因多态性及其联合效应与肺癌危险性的关系.方法 在PubMed数据库、EMBASE数据库、中国生物医学文献数据库(china biology medicine,CBM)和中国知识基础设施工程数据库(china national knowledge infrastructure,CNKI)中查询文献,时间范围从各数据库建库至2011年3月.使用STATA 10软件进行meta分析统计,对于每篇入选的文献均计算肺癌发生危险性调整混杂因素后优势比(odd ratio,OR)及其95%置信区间(confidence interval,CI).结果 15篇文献最终被纳入本次研究.Meta分析显示GSTMI基因缺失时CYPIA1基因Ile/Val位点为纯合突变型时肺癌发病风险明显高于杂合型与纯合突变型联合,总体OR分别为3.18(95%CI:1.27-7.98)和1.45(95%CI:1.08-1.94).GSTMl基因缺失时CYPIA1基因MsPI位点为纯合突变型时肺癌发病风险也高于杂合型与纯合突变型联合,总体OR分别为1.90(95%CI:1.00-3.58)和1.57(95%CI:1.23-2.00).结论 CYPIA1和GSTM1基因多态性联合作用增加了单个基因多态性发生肺癌的危险性.CYPIA1纯合突变型基因对人群肺癌易感性的影响明显大于野生型和杂合突变型.     

CAV-1基因多态性与散发乳腺癌易感性的相关性分析

[目的]探讨CAV-1基因多态性与散发乳腺癌的相关性。[方法]采用病例对照研究,纳入经病理确诊的135例女性乳腺癌患者作为实验组,166例女性健康体检者为对照组。通过竞争性等位基因特异性PCR法对研究对象基因位点进行分型;采用χ2检验比较CAV-1各SNP基因型及等位基因频率在两组中的分布差异;非条件Logistic回归分析CAV-1基因多态性与乳腺癌易感性的关联。[结果]在共显性模型、显性模型及等位基因模型下rs3807987及rs7804372位点多态性与乳腺癌易感性密切相关。rs3807987:相对于GG基因型,AG、AA基因携带者(AG/AA基因型)均增加乳腺癌的发病风险(P<0.05),OR值分别为2.110(95%CI:1.270~3.505)、1.968(95%CI:1.205~3.216)。rs7804372位点:相对于TT基因型,AT、AA基因携带者(AT/AA基因型)均增加乳腺癌的发病风险(P<0.05),OR值分别为2.088(95%CI:1.285~3.392)、2.059(95%CI:1.293~3.280)。rs12672038位点:在共显性模型、显性模型、等位基因模型均未见rs12672038位点多态性分布与乳腺癌发病风险之间存在相关性。[结论]CAV-1基因rs3807987与rs7804372多态性与乳腺癌易感性相关。     

CYP1A1、GSTM1基因多态性与肺癌易感性的研究

目的:探讨CYP1A1、GSTM1基因多态性与肺癌易感性之间的相关性。方法:利用RFLP-PCR(限制性片段长度多态性-聚合酶链反应)方法检测65例原发性肺癌和60例非肿瘤患者CYP1A1、GSTM1基因,再用NcoI及HinfI两种内切酶识别CYP1A1等位基因亚型。结果:1)肺癌组与对照组CYP1A1等位基因型Ile/Ile、Ile/Val、Val/Val的频率总体分布无显著性差异;但肺癌组CYP1A1(Val/Val)基因型频率(18.5%)明显高于对照组(8.3%),两组差异有显著性(P<0.05)。2)肺癌组GSTM1(-)基因型的频率(63.1%)明显高于对照组(45.0%),P<0.05。3)两种等位基因联合分析发现,与携带CYP1A1(Ile/Ile)/GSTM1(+)基因型的个体相比:CYP1A1(Ile/Ile)/GSTM1(-)以及CYP1A1(Ile/Val+Val/Val)/GSTM1(+)基因型个体患肺癌的风险度较高,OR分别为3.82(95.0%CI,1.27～11.45)和3.5(95.0%CI,1.18～10.41);而CYP1A1(Val/Val)/GSTM1(-)基因型个体患肺癌的风险度最高,OR为10.5(95.0%CI,1.70～64.73)。4)进一步分层分析发现,CYP1A1(Ile/Val+Val/Val)等位基因型主要增加鳞癌的危险性;而GSTM1基因型组织类型无明显的相关性。5)在分析吸烟对肺癌易感性的影响时发现,CYP1A1(Ile/Val+Val/Val)及GSTM1(-)等位基因型与吸烟有协同作用,并与至发病时的累积吸烟量有关。结论:CYP1A1(Val/Val     

ERα PvuⅡ 、XbaⅠ及CYP1A1 MspⅠ基因多态性联合作用与新疆维吾尔族女性乳腺癌发病相关性研究

摘 要：［目的］ 探讨ERα PvuⅡ 、XbaⅠ位点及CYP1A1 MspⅠ位点基因多态性与新疆维吾尔族女性乳腺癌易感性之间的相关性。［方法］ 应用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)检测190例维吾尔族女性乳腺癌患者及194例维吾尔族健康女性的ERα PvuⅡ 、XbaⅠ位点及CYP1A1 MspⅠ位点多态性,应用非条件Logistic回归分析其多态性及联合作用与新疆维吾尔族女性乳腺癌易感性的相关性。［结果］ 在共显性模型、显性模型、等位基因模型均未见ERα PvuⅡ位点多态性分布与乳腺癌发病风险之间的相关性;ERα XbaⅠ位点：相对xx基因型,Xx、XX、X基因携带者（Xx/ XX基因型）均显著增加乳腺癌发生风险（P<0.05）,OR值分别为5.029(95%CI：3.21～7.899)、16.500(95%CI：4.634～58.755)、5.500(95%CI：3.525～8.582)。CYP1A1 MspⅠ位点：相对于TT基因型,TC、CC、C基因携带者（TC/CC）均显著降低乳腺癌发病风险（P<0.05）,OR值分别为0.441(95%CI：0.284～0.683)、0.462(95%CI：0.238～0.898)、0.445(95%CI：0.293～0.676)。乳腺癌患者中,ERα PvuⅡ和XbaⅠ位点及CYP1A1 MspⅠ位点多态性与ER、PR、Her-2、淋巴结转移等乳腺癌临床病理特征之间存在相关关系（P<0.05）。ERα XbaⅠ及CYP1A1 MspⅠ两位点存在联合效应。［结论］ ERα XbaⅠ位点及CYP1A1 MspⅠ位点多态性与新疆维吾尔族女性乳腺癌患者易感性相关。     

CYP1A1多态性与肺癌遗传易感性的关系

目的探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon7多态性分布频率,并分析了Exon7多态性与中国四川汉族人群肺癌遗传易感性之间的相关性。结果CYP1A1Exon73种多态基因型分布频率在两组间比较差异无统计学意义,χ2=0.634,P=0.728。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺癌的危险性增加,OR=1.139,95%CI为0.635~2.042,P=0.662。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺鳞癌的风险显著增加,OR=3.510,95%CI=1.326~9.293,P=0.011。结论Val突变等位基因可能是中国四川汉族人群的肺癌易感基因。CYP1A1基因Exon7多态性在肺鳞癌发生中起重要作用。     

XRCC1基因单核苷酸多态性与食管癌易感性的关系

目的探讨X线修复交叉互补基因(X-ray cross complementing group1,XRCC1)单核苷酸多态性(single nucleotide polymorphism,SNPs)与食管癌易感性及临床病理的关系。方法应用Sequenom MassARRAY时间飞行质谱系统对200例食管癌及200例对照者XRCC1基因10个多态位点进行基因型分型。统计分析基因型频率和食管癌易感性的关系,统计基因多态与食管癌临床病理之间的关系。结果 XRCC1基因10个多态位点,rs25491位点、rs3213242位点没有多态性。条件Logistic回归分析显示,rs25487位点在显性模型中等位基因频率在病例组和对照组间差异有统计学意义(OR=1.558,95%CI=1.020-2.381,P=0.040);rs1799778位点在显性模型中等位基因频率在病例组和对照组间差异有统计学意义(OR=1.558,95%CI=1.019-2.381,P=0.041);rs2682585位点基因频率在病例组和对照组间差异有统计学意义(OR=14.313,95%CI=5.188-39.489,P=0.000);其余位点两组间差异无统计学意义。没有发现有意义的单体型。未发现基因多态与食管癌临床病理特征之间的关系。结论 XRCC1基因SNP位点rs2682585、rs25487和rs1799778与食管癌发病风险有显著相关性,很可能是决定食管癌个体遗传易感性的重要因素,以上3个SNP位点与食管癌临床病理特征之间无相关性。     

Association of CYP1A1 rs1048943 Polymorphism with Prostate Cancer in Iraqi Men Patients

Objective: The purpose of this study was to evaluate the relationship between CYP1A1 gene rs1048943 polymorphism and the risk of Iraqi men with prostate cancer. Methods: In this research, we conducted a population-based approach that intersects high-throughput genotype information from  different population of Iraq to estimate the frequency of genotypes associated with prostate cancer responsivenessOur study included a total of 100 patients and 150 healthy controls. rs1048943 genotyping has been investigated in Iraqi men in connection with prostate cancer. Results: We observed that individuals with the rs1048943 GA genotype had an increased risk of prostate cancer relative to those with the AA genotype  ( OR 95% CI of 0.449 :95%CI 0.23-0.90; P = 0.002). We found in the dominant model that the rs1048943 GA and GG genotype displayed an increased risk of prostate cancer relative to the AA genotype   ( OR 95% CI of 0.680 :95%CI 0.4-1.17; P = 0.018). Conclusion: Polymorphism RS 1048943 in the CYP1A1 gene is associated with the risk of developing prostate cancer and is possibly one of the most significant factors in its development.     

CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.     

谷胱甘肽转硫酶T1、M1基因型和烟酒茶嗜好与食管癌、胃癌

目的 :研究谷胱甘肽转硫酶T1、M1(GSTT1、GSTM 1)基因多态性和烟酒茶嗜好及其相互作用与食管癌、胃癌易感性的关系。方法 :在上消化道癌高发区淮安市进行了病例 -对照研究 (食管癌 141例 ,胃癌 15 3例 ;人群对照 2 2 3例 ) ,调查研究对象的烟酒茶嗜好习惯 ,以多重PCR方法分析GSTT1、GSTM1基因型。结果 :食管癌组GSTM1-基因型频度 (75 .18% )显著高于对照组 (5 9.6 4 % ,P =0 .0 0 2 4 ;多因素调整OR =2 .33,95 %CI =1.39～ 3.92 )。吸烟或不饮茶与GSTM 1 基因型在增加食管癌发生的风险中有明显的协同作用。在GSTT1 基因型者中 ,吸烟习惯显著增加食管癌、胃癌的危险性 ;在GSTM1 基因型者中 ,经常饮酒显著增加食管癌、胃癌的危险性。结论 :食管癌、胃癌的发生与生活习惯、GSTM1和GSTT1基因型以及它们的相互作用有关。     

CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case–control study within a large‐scale population‐based prospective study

Cytochrome P450 (CYP) 1A1 and glutathione S‐transferases (GST) M1 and T1 are major enzymes in the carcinogen metabolizing pathway. We examined the association between single nucleotide polymorphisms (SNPs) of CYP1A1 (rs4646421, rs4646422 and rs1048943), GSTM1 and GSTT1 and gastric cancer risk in Japan. This is a nested case–control study (457 cases and 457 matched controls) of our population‐based cohort involving 36,745 subjects who answered a baseline questionnaire and supplied blood samples. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression models. We found that CYP1A1 (rs4646422) variant allele was associated with a statistically significant increased risk of gastric cancer compared with the homozygous wild‐type genotype (OR = 1.65; 95% CI = 1.17–2.32). GSTM1 null, GSTT1 null and GSTM1/T1 both or either null genotypes were associated with increased risk, but not statistically significantly. Combination of the CYP1A1 (rs4646422) variant allele and GSTM1/T1 both or either null genotypes was associated with a statistically significant increased risk compared with the combination of the CYP1A1 homozygous wild‐type genotype and the GSTM1/T1 both active genotypes. In addition, compared with CYP1A1 (rs4646422) homozygous wild‐type genotypes in those who were never‐smokers, CYP1A1 variant alleles in those who smoked ≥30 pack‐years were associated with an increased risk; neither gene–gene nor gene–environment interactions were significant. The CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population.     

hCHK2基因tagSNPs位点及单体型与新疆哈、汉族食管癌关系的研究

目的：探讨新疆哈萨克族、汉族食管癌患者hCHK2基因rs2278022、rs2602431和rs29700773个tagSNPs位点及其单体型与食管癌易感性的关系。方法：以聚合酶链式反应-连接酶检测反应（PCR-LDR）技术,分析239例食管癌患者（其中哈族132例,汉族107例）和作为对照的513例非食管癌患者（其中哈族309例,汉族204例）hCHK2基因rs2278022、rs2602431和rs29700773个tagSNPs位点基因型的分布;利用SHEsis软件分析其构成的单体型在病例组和对照组中的分布频率,比较基因型和单体型在病例组和对照组间的分布差异。结果：在哈族和汉族人群中,hCHK2基因rs2278022、rs2602431和rs2970077位点基因型和等位基因的频率分布在病例组和对照组间的差异无统计学意义（P均〉0.05）,其3个tagSNPs位点及其单体型,在哈族和汉族的病例组与对照组中的频率分布的差异均无统计学意义（P均〉0.05）。结论：hCHK2基因rs2278022、rs2602431和rs2970077等3个tagSNPs位点及其单体型与哈萨克族和汉族食管癌易感性无关。     

Meta-Analysis of Polymorphic Variants Conferring Genetic Risk to Cervical Cancer in Indian Women Supports CYP1A1 as an Important Associated Locus

Objective: Association of multiple polymorphic variants with cervical cancer has been elucidated by severalcandidate gene based as well as genome-wide association studies. However, contradictory outcomes of those studieshave failed to estimate the true effect of the polymorphic variants on cervical cancer. Methods: Literature mining ofthe PubMed database was done to gather all the publications related to genetic association with cervical cancer in India.Out of 98 PubMed hits only 29 genetic association studies were selected for meta-analysis based on specific inclusioncriteria. A fixed-effect meta-analysis was performed to evaluate the overall association of the genetic polymorphismswith cervical cancer. Cochran’s Q test was performed to assess between study heterogeneity. Publication bias wasalso estimated by funnel plots and Egger’s regression test. Further, sub-group analysis was conducted by fixed-effectmeta-regression to assess the impact of polymorphisms on cervical cancer in the presence of Human Papilloma Virus(HPV). Result: Following a fixed-effect model, meta-analysis was conducted that revealed 2 polymorphic variantsviz. ‘deletion polymorphism (Del2) (OR=1.79, 95% CI= 1.08-2.95, P=0.023) in GSTM1’ and ‘rs1048943 (OR = 2.34,95% CI=1.37-3.99, P=0.0018) in CYP1A1’ to be associated with cervical cancer. However, multiple testing correctionshowed only rs1048943 of CYP1A1 to be significantly associated (P-value=0.029) with cervical cancer with significantpublication bias (P-value=0.0113) as estimated by Egger’s regression test. The polymorphic variants ‘rs1801131’,‘rs1801133’, ‘rs2430561’, ‘rs1799782’, ‘rs25486’ and ‘rs25487’ showed significant (p<0.05) evidence of heterogeneitybetween studies by Cochran’s Q test and also by heterogeneity index (I2) calculation. Conclusion: Therefore, our studyrevealed significant association of rs1048943 in CYP1A1, but a nominal association of deletion polymorphism (Del2)in GSTM1 with cervical cancer, which provides a comprehensive insight on the true effect of the polymorphisms,reported in various case-control studies, on the risk of the development of cervical cancer in Indian women.     

Sequence Polymorphism in Xenobiotic Metabolising Genes in Iraqi Colorectal Cancer Patients

Objectives: Colorectal cancer (CRC) is the third most prevalent malignant neoplasm. Genetic variations in the xenobiotic metabolising cytochrome enzymes. Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in cancer pathogenesis and prognosis. The aim of this work is to determine the frequency of Single Nucleotide Polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI and rs4646903/MSP1) and CYP1B1 (rs1056836, Leu432Val) genes in patients with CRC cancer. It was also an attempt to identify the association between SNPs and CRC and its stage and grade at diagnosis. Methods: This case-control study was conducted in Kirkuk/Iraq, 200 patients with CRC and 200 cancer free control subjects were enrolled. Genomic DNA was extracted from venous blood samples and screened for SNPs using Restriction Fragment Length  Polymorphism (RFLP) and confirmed by the direct DNA sequencing. Results: The reference genotype of CYP1A1 gene rs1048943 is AA. Both the AG and GG variants were  significantly more frequent in the cancer group and associated with increased risks of CRC and its later stages (stages III and IV)  and poor  differentiation (p <0.01). The reference genotype of CYP1A1 rs4646903 is TT. The variant genotypes, TC and CC, had no significant association with increased odds of cancer (P>0.05) or with tumour stage or its grade (p>0.05). The GG genotype of CYP1B1 rs1056836 was the reference genotype. The CG and CC variants were not associated with increased risks of CRC (P>0.05) or its stage or grade except the CG genotype which was associated with poor differentiation (OR= 3.4, 95 % CI= 1.8 -6.5, p <0.001). Conclusion: CYP1A1 gene rs1048943 SNPs can represent a potential future marker for   CRC risk prediction and prognosis. Further evaluation in large scale studies will provide greater understanding of the effects of other genes SNPs on CRC  risk and prognosis.     

Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in Chilean individuals

Polycyclic aromatic hydrocarbons (PAHs) contained in tobacco smoke acquire carcinogenicity following their activation by xenobiotic-metabolizing enzymes to highly reactive metabolites. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these PAHs, and GSTM1 is the main enzyme responsible for its detoxification. CYP1A1 and GSTM1 polymorphisms were evaluated in 124 Chilean healthy controls and 48 oral cancer patients through PCR-based restriction fragment length polymorphism. In the healthy controls, frequencies of the CYP1A1 variant alleles for m1 (CYP1A1(*)2A) and the GSTM1null genotype were found to be 0.25 and 0.19, respectively. In the oral cancer patients, these frequencies were 0.33 and 0.50, respectively. Thus, the GSTM1 and m1 rare alleles were significantly more frequent in the oral cancer patients compared to the controls. The estimated relative risk for oral cancer associated with the single genotype CYP1A1 or GSTM1 was 2.08 for wt/m1, 1.04 for m1/m1 and 4.16 for the GSTM1null genotype. For smokers, the estimated relative risk (adjusted by age and gender) was higher in the individuals carrying the m1 allele of CYP1A1 [wt/m1: odds ratio (OR)=5.68, P=0.0080; m1/m1: OR=7.77, P=0.0420] or GSTM1null genotype (OR=20.81, P<0.0001). Combined genotypes CYP1A1 and GSTM1 increased the risk significantly (wt/m1/GSTM1null: OR=19.14, P=0.0030; m1/m1/GSTM1null: OR=21.39, P=0.0130). Taken together, these findings suggest that Chilean individuals carrying single or combined GSTM1 and CYP1A1 polymorphisms may be more susceptible to oral cancer induced by environmental tobacco smoking.     

Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan

BACKGROUND: The p53 mutation spectrum of prostate cancers developing in Japan indicates a role for environmental factors. This suggests there might be differences in susceptibility due to genetic polymorphisms in metabolic activation enzyme genes. We analyzed genetic polymorphisms of the xenobiotic-metabolizing enzymes, CYP1A1 and GSTM1. METHOD: Genotyping of CYP1A1 and GSTM1 was investigated by using allele-specific PCR in 115 prostate cancer (PCa) patients and 204 control patients. RESULTS: The CYP1A1 Val/Val genotype significantly increased the risk for PCa (OR = 2.6; 95% CI = 1.11-6.25) and the Ile/Val genotype showed a similar tendency (OR = 1.4; CI = 0.86-2.29). Individuals with the GSTM1 (0/0) genotype demonstrated a slightly increased risk (OR = 1.3; CI = 0.82-2.04). The combination of the CYP1A1 Val allele and GSTM1 (0/0) genotype was associated with a higher risk (OR = 2.3; CI = 1.18-4.48) than the CYP1A1 Val allele alone. When cases were analyzed by age at initial diagnosis, the relative risks with both the CYP1A1 Val allele and the GSTM1 (0/0) genotype were higher in the young group than in the old group (CYP1A1; OR = 1.7, CI = 0.89-3.17: GSTM1; OR = 1.6, CI = 0.84-2.99). The frequency of the GSTM1 (0/0) genotype was also higher in patients with advanced stage disease. In stage D, the OR was 1.7 with a CI of 0.93-3.17 and in stages A and B, the OR was 0.8 with a CI of 0.40-1.62. CONCLUSIONS: These results suggest that CYP1A1 and GSTM1 polymorphisms are linked to a propensity for PCa development.      

Interaction of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferase M1 to breast cancer in Taiwanese woman without smoking and drinking habits

P450 (CYP) and glutathione S-transferase (GST) are involved in the activation and detoxification of many potential carcinogens. Although, the interaction between environmental exposure and genetic polymorphisms of cytochrome P450 2E1 (CYP2E1) and glutathione S-transferase M1 (GSTM1) in breast cancer has been assessed, the gene–gene interactions between CYP2E1 and GSTM1 related to breast cancer have not been focused on and reported. We conducted a hospital-based case-control study to investigate whether the genetic interaction effects of CYP2E1 and GSTM1 modify the risk of developing breast cancer independent of the effect of cigarette smoking and alcohol consumption. Individuals with the C2/C2 genotype of CYP2E1 had a lower risk (OR = 0.24, 95% CI = 0.08–0.74) when compared with those with the C1/C1 genotype. However, there was no significant difference (OR = 1.05, 95% CI = 0.73–1.50) in the GSTM1 genotype frequency between the cases with breast cancer and that of the controls. When individuals with the genotype of C1/C1 or C1/C2 of CYP2E1 and the wild-type of GSTM1 were compared with those of C2/C2 of CYP2E1 and the null-type of GSTM1 however, we found a significantly increased risk (OR = 3.50, 95% CI = 1.01–16.55) in the breast cancer patients. Our findings indicated a gene–gene interaction between CYP2E1 and GSTM1 was accessible to developing breast cancer in Taiwanese women without the habits of cigarette smoking and alcohol consumption even though independent effects of CYP2E1 and GSTM1 were weak or non-significant and suggest that environmental carcinogen besides cigarette and alcohol consumption could induce breast cancer.Szu-Hsien Wu and Shih-Meng Tsai contributed equally to this work.