Association between CYP2E1 genetic polymorphisms and lung cancer risk: A meta-analysis

Genetic variations in metabolic genes are thought to modify the metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we assessed reported studies of associations between polymorphisms of CYP2E1 RsaI/PstI and DraI, and the risk of lung cancer. We found decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2 + c2/c2 genotype [odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.72–0.89 and OR = 0.82, 95% CI: 0.72–0.93, respectively], using 4436 cases and 6385 controls from 26 studies. We also observed a decreased lung cancer risk among subjects carrying c1/c2 and c1/c2 + c2/c2 genotypes in the Asian population and on the basis of population control in stratified analysis. We found a protective effect of the CYP2E1 DraI CC and CD + CC polymorphisms for lung cancer (OR = 0.58, 95% CI: 0.41–0.81 and OR = 0.84, 95% CI: 0.73–0.96, respectively). The meta-analysis suggests that CYP2E1 RsaI/PstI and DraI polymorphisms may affect the susceptibility of lung cancer, and a study with a larger sample size is needed to further evaluate gene–environment interaction on CYP2E1 polymorphisms and lung cancer risk.     

Association between genetic polymorphisms of CYP1A2, arylamine N-acetyltransferase 1 and 2 and susceptibility to cholangiocarcinoma.

Human CYP1A2 and arylamine N-acetyltransferases, which are encoded by the polymorphic CYP1A2 and NAT genes respectively, have been shown to have wide interindividual variations in metabolic capacity and may be potential modifiers of an individual's susceptibility to certain types of cancers. The present study aimed to evaluate the relationship between CYP1A2, NAT1 and NAT2 polymorphisms and cholangiocarcinoma (CCA), the most prevalent cancer in the north-east of Thailand. A total of 216 CCA patients and 233 control subjects were genotyped by polymerase chain reaction with restriction fragment length polymorphism based assays. Two CYP1A2 alleles (CYP1A2*1A wild-type and *1F), six NAT1 alleles (NAT1*4 wild-type, *3, *10, *11, *14A and *14B) and seven NAT2 alleles (NAT2*4 wild-type, *5, *6A, *6B, *7A, *7B and *13), which are the major alleles found in most populations, were analysed. Although CYP1A2*1A allele, NAT1*10 allele, and the NAT2 slow acetylator alleles were not associated with CCA risk, among the male subjects, the genotype CYP1A2*1A/*1A conferred a decreased risk of the cancer (adjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.08-0.94) compared with CYP1A2*1F/1*F. Frequency distributions of rapid NAT2*13 and two slow alleles (*6B and *7A), but not the other major alleles, were associated with lower CCA risk. Adjusted OR of the genotypes consisting of at least one of these alleles significantly decreased the cancer risk compared with none of them (OR 0.26, 95% CI 0.15-0.44). This study suggests that the NAT2 polymorphism may be a modifier of individual risk to CCA.     

Ethnic susceptibility to lung cancer: differences in CYP2E1, CYP1A1 and GSTM1 genetic polymorphisms between French Caucasian and Chilean populations.

Many investigators have reported an association between genetic polymorphisms of cytochromes P-450 CYP2E1, CYP1A1 or glutathione S-transferase Mu (GSTM1) and susceptibility to lung cancer. However, pronounced interethnic variations have been described in the frequencies of these polymorphisms, especially between Asians and Caucasians. The present study was set up to establish CYP2E1 (c1, c2 and C, D), CYP1A1 (m1, m2 and Ile, Val) and GSTM1 (null) allelic frequencies in Chileans (n = 96) who are an admixture of Native Americans and Caucasians (Spaniards). The rare allele frequencies were found to be 0.15 (c2), 0.21 (C), 0.23 (m2), 0.32 (Val) and 0.21 ('null' genotype). These values are significantly higher than those of Caucasians except for the GSTM1 'null' genotype and suggest differences in susceptibility to lung cancer between both populations.     

MGMT基因多态性与前列腺癌易感性的Meta分析

目的:探讨6-甲基鸟嘌呤甲基转移酶(6O-methylguanine-DNA methyltransferase,MGMT)基因多态性与前列腺癌（prostate cancer,PCa）发病易感性的关联。方法:通过检索PubMed、CNKI和万方数据库从1970年1月1日至2016年12月31日国内外已经公开发表的中、英文献,筛选合格文献行Meta分析。结果:最终纳入关于MGMT基因多态性与PCa易感性关联的病例-对照研究11项,共计病例组5 143例,对照组8 118例。Meta分析结果显示,MGMT基因rs12917多态性位点与PCa显著相关(TT vs CC:P=0.047,TT vs CC+CT:P=0.038)。以种族进行亚组分析显示,MGMT基因rs12917多态性位点在亚洲人中与PCa显著相关（T vs C:P=0.008,TC vs CC:P=0.013,TC+TT vs CC:P=0.009,TC vs CC+TT:P=0.014）。然而MGMT基因的rs2308327和rs2308321多态性位点和PCa的易感性无关。结论:本Meta分析结果认为MGMT基因rs12917多态性位点与PCa的易感性相关,可作为PCa患者潜在的诊断、筛查分子标志物。     

Association of GSTM1, CYP1A1 and CYP2E1 genetic polymorphisms with susceptibility to lung adenocarcinoma: a case-control study in Chinese population

A case-control study of 164 lung adenocarcinoma (AC) patients with 181 age- and gender-matched healthy controls was conducted in order to assess any associations between glutathione- S -transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cyto-chrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp 1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340–0.837)]. Furthermore, 3.0-fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa 1 wild type versus those with combined GSTM1 non-null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa 1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC. (Cancer Sci 2003; 94: 448–452)     

Association of CYP1B1 polymorphisms and breast cancer risk.

Cytochrome P450 1B1 catalyzes the conversion of 17-beta-estradiol (E2) to thecatechol estrogen metabolites 2-OH-E2 and 4-OH-E2 that have been postulated to be involved in mammary carcinogenesis. We sought to determine whether two common functional polymorphisms in Cytochrome P450 1B1, V432L (m1), and A453S (m2) are related to breast cancer risk. Using a nested case control design within the Nurses' Health Study cohort, we genotyped 453 cases and 456 controls and found no significant association between m1[val/leu and leu/leu versus val/val, OR = 1 (CI, 0.72-1.45)] or m2 [asn/ser and ser/ser versus asn/asn, OR = 0.8 (CI, 0.62-1.15)] and breast cancer risk. However, we did observe women with the Val/Val (m1) genotype to have a higher percentage of estrogen receptor-positive tumors (P = 0.03). We did not observe any correlation with the m2 genotypes and estrogen receptor status. The association of the m1 and m2 genotypes on plasma hormone levels in postmenopausal control women not using hormone replacement therapy was also evaluated. Carriers of the m1 leu and m2 ser alleles had modestly higher estradiol levels but similar estrone and estrone sulfate levels. The results presented do not support a strong association between m1 and m2 and the risk of breast cancer.     

Genetic polymorphisms of the CYP2E1 gene do not contribute to oral cancer susceptibility in south Indians

Cytochrome P450 (CYP) is a super family of mixed-function oxidases that are responsible for the human metabolism of drugs and endogenous compounds, as well as environmental and dietary substances. Many CYP enzymes function in the liver, but presence of CYP2E1 in the brain is demonstrating its role in both nicotine and ethanol metabolism. To examine the association between CYP2E1 polymorphism and the risk of oral cancer, we performed a case-control study on a south Indian population. 157 patients with oral cancer and 132 age and sexmatched controls were recruited. Three SNPs of the CYP2E1 gene [4768G>A (p. V179I, dbSNP rs6413419), CYP2E1-1295G>C (dbSNP rs3813867) and CYP2E1_-1055C>T (dbSNP rs2031920)] were genotyped using TaqMan allelic discrimination. The V179I locus is monomorphic in the study subjects, whereas rs3813867 and rs2031920 are co-inherited with a minor allele frequency of 0.022. None of the polymorphic sites deviated from HWE in controls. A much lesser frequency of the uncommon c2 allele was seen in our control subjects than in Caucasians and East Asians. There were no significant differences between oral cancer and controls in the distribution of either allelic or genotype frequencies. None of the haplotypes showed a significant association with oral cancer. Our results suggest that CYP2E1 is not a major or independent determinant in the pathogenesis of oral cancer in south Indians.     

CYP2E1基因多态性与客家人群胃癌易感性的研究

目的：通过研究细胞色素P4502E1（CYP2E1）基因多态性位点rs2031920与客家人群胃癌遗传易感性的相关性,探讨遗传和环境因素在胃癌发病中的作用。方法采取病例-对照研究,选择经胃镜和病理检查确诊的梅州地区客家人群51例胃癌患者（胃癌组）和52例正常对照（对照组）,对CYP2E1 rs2031920（C-1053T）位点进行基因型及等位基因检测,分析其在两组间的分布特征。结果CYP2E1 rs2031920位点在梅州地区客家人群中存在 CC、CT、TT 多态性,各基因型在胃癌组的分布频率为62．75％（32／51）、33．33％（17／51）、3．92％（2／51）,在对照组的分布频率为59．62％（31／52）、34．61％（18／52）、5．77％（3／52）,两组之间的差异无统计学意义（χ2＝0．235,P ＝0．889）。CYP2E1基因rs2031920位点的等位基因 C、T 在胃癌组和对照组构成比分别为79．41％（81／102）、20．59％（21／102）和76．92％（80／104）、23．08％（24／104）,差异无统计学意义（χ2＝0．186,P ＝0．666）。经性别、年龄分层分析结果显示也无统计学意义（χ2＝4．412,P ＝0．129;χ2＝0．898,P ＝0．473）。结论 CYP2E1的基因多态性位点 rs2031920与客家人群胃癌的易感性不相关。     

DNA连接酶基因LIG1多态性与肺癌易感性研究

背景与目的: 肺癌是由环境和遗传两大类因素联合作用导致的复杂疾病,其中DNA损伤是肺癌遗传病因中的重要组分.作为参与多条DNA损伤修复通路的关键因子,DNA连接酶与肺癌发生可能存在联系.本文旨在研究DNA连接酶基因LIG1外显子6多态性与肺痛易感性的关系,并探索其与吸烟可能的交互作用.方法: 采用病例-对照研究,收集原发性肺癌患者396例为病例组,同时随机抽取465名当地健康居民作为对照组,进行流行病学调查.运用PCR-RFLP方法分析LIG1基因外显子6的多态性.应用Logistic回归模型分析该位点多态性与肺癌易感性的关系.结果: 突变等位基因C在病例组和对照组中的频率分别为28.41%和26.02%,两组间差异无显著性(P=0.2667).相对于野生型A/A,携带A/C基因型者患肺癌的危险度为1.20(95%CI:0.90～1.62);而患肺腺癌和肺鳞癌的危险度分别达到1.45(95%CI:0.93～2.26)和1.57(95%CI:0.93～2.65).在肺腺癌的发病中,LIGI多态的突变基因型与吸烟之间存在临界显著的负交互作用(OR=0.44,95%CI=0.18～1.06).结论: DNA连接酶基因LIG1外显子6多态性可能与肺腺癌和肺鳞癌的易感性有关.     

中国汉族人群DNA聚合酶ε基因POLE1单核苷酸多态性与肺癌易感性的关系

目的：探讨人类DNA聚合酶ε基因POLE1单核苷酸多态性（SNP）与肺癌易感性间的关系。方法：采用病例对照研究方法,选择经组织学确诊的肺癌患者462例,以及相同地区,性别年龄频数匹配的对照466例,针对经筛选的5个SNP进行基因型检测,通过统计分析研究基因频率与肺癌风险的关系,并探讨吸烟在其中的影响。结果：病例组rs5744738基因频率分布高于对照组（P〈0.05）。A/A纯合变异携带人群的患肺癌风险显著降低（校正OR=0.47,95%CI：0.25～0.91）。在分层分析中,60岁以上人群患肺癌的风险显著下降（校正OR=0.28,95%CI：0.09～0.91）,无患肿瘤家族史人群下降到0.42倍（校正OR=0.42,95%CI：0.19～0.90）。随着吸烟量的增加,G/G或G/A基因型人群肺癌风险显著升高。rs5744962变异位点（T→C）可提高非吸烟人群的患肺癌风险至1.75倍（95%CI：1.02～3.00）。结论：选取的5个人类POLE1基因SNP的多态性可能与中国汉族人群肺癌遗传易感性有关,在携带rs5744738及与之紧密连锁的rs4883545、rs5744873突变纯合基因的人群,患肺癌的风险显著降低,而携带rs5744962、rs5745047突变基因位点的非吸烟人群患肺癌的风险升高。     

CYP1A1 CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus

We investigated the genetic polymorphisms of CYPIAI, CYP2EI and GSTMI in Japanese esophageal cancer patients (n = 53) with a histological diagnosis of squamous-cell carcinoma, to determine whether susceptibility to esophageal cancer is associated with these polymorphisms. There were no significant differences in the frequency distribution of any one of the 3 polymorphisms between esophageal cancer patients and 132 healthy Japanese controls. The genotype distributions in tobacco smokers or alcohol drinkers were also quite similar for male patients and male controls. The age at onset of esophageal cancer was also similar for patients with any genotype of the 3 polymorphisms. We conclude that the 3 polymorphisms are unlikely to be associated with esophageal cancer susceptibility. Int. J. Cancer 71:192–195, 1997. © 1997 Wiley-Liss, Inc.     

Genetic polymorphisms in cytochrome P450 (CYP) 1A1, CYP1A2, CYP2E1, glutathione S-transferase (GST) M1 and GSTT1 and susceptibility to prostate cancer in the Japanese population

Associations between genetic polymorphisms of CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1 and prostate cancer (PCa) were analyzed in a case-control study of 315 individuals. The frequency of valine (Val)/valine (Val) genotypes for CYP1A1 was 11.3% in cases compared with 5.5% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (odds ratio=2.4, 95% confidence interval (CI)=1.01-5.57). No links were detected between PCa and polymorphisms in other enzymes. However, the combination of CYP1A1 (Ile/Val and/or Val/Val) polymorphisms with the GSTM1 null type resulted in an OR of 2.2 (CI=1.10-4.57, 1.12-4.20, respectively). This study suggests that the CYP1A1 polymorphism and its combination with GSTM1 may be associated with PCa susceptibility in the Japanese population.     

甘肃省人群CYP2E1基因多态性与急性白血病易感性的关系

目的 研究甘肃省人群CYP2E1基因多态性和急性白血病易感性的关系.方法 用1∶1配对病例-对照方法,LDR-PCR方法,对甘肃省人群中100例急性白血病患者和100例对照进行CYP2E1基因突变分析.结果 急性白血病组CYP2E1基因C2等位基因频率(13.5%)和CIC2+C2C2基因型频率(22%)均高于对照组(10.5%和19%),但其差异均无统计学意义.进一步分层分析,急性髓系白血病(AML)组C1C2/C2C2基因型频率(27%)高于对照组(19%),其差异无统计学意义.急性淋巴细胞白血病(ALL)组CYP2E1基因C2等位基因频率和C1C2/C2C2基因型频率均与对照组差异无统计学意义(x2=0.446,P=0.504>0.05).结论 甘肃省研究人群CYP2E1基因多态性与急性白血病(AML和ALL)遗传易感性无关.     

CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people.

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(-) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(-). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR=6.28; m2/GSTM1(-), OR=3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/C, OR=1.39; m2/c2, OR=2.00; val/C, OR=1.45; val/c2, OR=0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(-), 7.38 for m2/val and 3.68 for m2/GSTM1(-), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.     

CYP1A1和NQO1及EPHX1基因多态性与膀胱癌易感相关性分析

目的:探讨细胞色素P450 1A1(CYP1A1)、依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶1(NQO1)和环氧化物水解酶(EPHX1)基因多态性与浙江地区膀胱癌易感性的关系.方法:采用病例对照研究方法,应用相对的2对引物-聚合酶链反应技术(PCR-CTPP),对99例膀胱癌患者和100例非肿瘤患者的CYP1A1 A4889G、NQO1 C609T和EPHX1 A416G基因型进行检测,并分析其与膀胱癌易感性的关系.结果:NQO1 C609T基因型分布频率在膀胱癌组和对照组之间的差异有统计学意义,P＜0.05;携带609TT基因型的个体罹患膀胱癌的风险是携带609CC基因型个体的2.448倍(95％CI为1.125～5.326).CYP1A1 A4889G和EPHX1 A416G基因型分布频率在两组间的差异均无统计学意义,P＞0.05.携带NQO1 609TT与EPHX1 416AA两高危基因型的个体罹患膀胱癌的风险是同时携带两低危基因型个体的4.181倍(95％CI为1.465～11.934).相类似的,携带CYP1A1 4889AG/GG、NQO1 609TT与EPHX1 416AA三高危基因型的个体罹患膀胱癌的风险则为4.765倍(95％CI为0.895～25.364).结论:NQO1 C609T基因多态性可能与膀胱癌的易感性相关,携带NQO1 609TT基因型的人群易患膀胱癌.而且,基因与基因(NQO1 609TT与EPHX1 416AA,CYP1A1 4889AG/GG、NQO1 609TT与EPHX1 416AA)的交互作用增加了这种风险.     

Association of CYP2E1 gene polymorphism with predisposition to cancer development

We summarize research results on association of cytochrome P450 2E1 (CYP2E1) genetic polymorphisms with the development of ecologically determined cancers. Cytochrome P450 monooxygenase enzyme system is involved in metabolic activation of procarcinogens, which is an important stage during normal cell transformation into a malignant one. Studies of association between CYP2E1 gene polymorphisms and the risk of cancer development are of particular interest, since the enzyme participates in bio-transformation of numerous procarcinogens. We place special emphasis on characterization of known CYP2E1 polymorphisms and analysis of their role in pathogenesis of various cancer types. Results obtained provide evidence on association of CYP2E1 genetic polymorphisms both with increased and decreased risk of development of malignant tumors. Ethnic and geographic peculiarities were also identified for frequencies of CYP2E1 variants distribution.     

Association between microsomal epoxide hydrolase 1 polymorphisms and susceptibility to esophageal cancer: a meta-analysis

Microsomal epoxide hydrolase 1 (EPHX1) plays an important role in the detoxification of carcinogenic polycyclic aromatic hydrocarbons. EPHX1 Tyr113His and His139Arg polymorphisms have been reported to have some impacts on the EPHX1 activity. Previous case–control studies assessing the associations between EPHX1 polymorphisms and esophageal cancer risk reported conflicting results. To quantitatively summarize the associations of EPHX1 Tyr113His and His139Arg polymorphisms with esophageal cancer risk, a systemic review and meta-analysis of published studies were performed. Published literatures from PubMed, Embase, and China National Knowledge Infrastructure databases were searched. The strength of the associations between EPHX1 polymorphisms and esophageal cancer risk was estimated by the pooled odds ratios (ORs) with its 95 % confidence interval (95 %CI). This meta-analysis yielded nine case–control studies, which included nine studies for Tyr113His polymorphism (1,291 cases and 2,120 controls) and seven studies for His139Arg polymorphism (899 cases and 1,615 controls). Overall, meta-analysis showed that EPHX1 Tyr113His polymorphism was not associated with esophageal cancer risk under all genetic models. Meta-analysis of these seven studies for EPHX1 His139Arg polymorphism showed that EPHX1 His139Arg polymorphism was also not associated with esophageal cancer risk under all genetic models. However, subgroup analysis by ethnicity further showed that there was an obvious association between EPHX1 His139Arg polymorphism and decreased risk of esophageal cancer in Caucasians (ArgArg versus HisArg/HisHis: OR?=?0.52, 95 %CI 0.27–0.97, P?=?0.041). This meta-analysis suggests that EPHX1 His139Arg polymorphism is associated with decreased risk of esophageal cancer in Caucasians. In addition, more studies with large samples are needed to get a more precise estimation on the associations mentioned above.     

Association of CYP1A1, CYP1A2, GSTM1 and NAT2 gene polymorphisms with colorectal cancer and smoking.

We investigated CYP1A1*2A, CYP1A1*2C, CYP1A2*1C, CYP1A2*1F, GSTM1 and NAT2 gene polymorphisms, involving enzymes which metabolize many carcinogens, with reference to colorectal cancer risk. The distribution of these genotypes was not associated with risk overall. However, the CYP1A1*2A T/C genotype showed a significant association with colorectal cancer risk in never-smokers (odds ratio [OR], 3.06; 95% confidence interval [95% CI], 1.11-8.40; p = 0.030). The risk of the NAT2 rapid genotype in never-smokers was also statistically significantly increased (OR, 5.38; 95%CI, 1.80-16.1; p = 0.003). Furthermore, the joint effects of NAT2 rapid plus other genotypes were associated with colorectal cancer overall (OR, 3.12; 95%CI, 1.15-8.51; p = 0.026, for NAT2 rapid plus combined CYP1A1*2C Ile/Val and Val/Val, OR, 3.25; 95%CI, 1.09-9.74; p = 0.035, for NAT2 rapid plus CYP1A2*1C G/G, and OR, 4.20; 95%CI, 1.09-16.1; p = 0.037, for NAT2 rapid plus GSTM1 null, respectively). In never-smokers, the joint effects of NAT2 rapid plus other genotypes were remarkable (OR, 15.9; 95%CI, 1.87-135.8; p = 0.011, for NAT2 rapid plus combined CYP1A1*2A T/C and C/C, OR, 5.71; 95%CI, 1.49-21.9; p = 0.011, for NAT2 rapid plus combined CYP1A1*2C Ile/Val and Val/Val, and OR, 9.14; 95%CI, 2.05-40.7; p = 0.004, for NAT2 rapid plus CYP1A2*1F A/A, respectively). The joint effect of CYP1A2*1F A/A plus CYP1A2*1C G/G genotypes was also increased in never-smokers (OR, 6.16; 95%CI, 1.26-30.1; p = 0.025). Our findings suggest that the CYP1A1*2A T/C and NAT2 rapid genotypes is associated with colorectal cancer susceptibility without smoking exposure. These results also indicate that the NAT2 in combination with CYP1A1*2C, CYP1A2*1C, or GSTM1 genotypes may strongly confer susceptibility to colorectal cancer. In particular, the combination of NAT2 plus CYP1A1*2A, CYP1A1*2C, or CYP1A2*1F genotypes, and that of CYP1A2*1F plus CYP1A2*1C genotype may define a group of persons who are genetically susceptible to colorectal cancer in never smokers.