Association between NQO1 C609T polymorphism and colorectal cancer risk

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme, and the NQO1 C609T polymorphism is associated with the enzymatic activity of NQO1. Many studies were performed to assess the association between NQO1 C609T polymorphism and colorectal cancer risk, but no consensus was available up to now. We conducted a meta-analysis to examine the association between NQO1 C609T polymorphism and colorectal cancer risk, and the pooled odds ratios (OR) with their 95 % confidence intervals (95 % CI) were used to assess the association. Finally, 12 studies involving 4,026 cases and 4,855 controls were included into the meta-analysis. Overall, there was an obvious association between NQO1 C609T polymorphism and colorectal cancer risk (T versus C: OR?=?1.28, 95 % CI 1.08–1.51, P?=?0.005; TT versus CC: OR?=?1.60, 95 % CI 1.10–2.33, P?=?0.015; TT/CT versus CC: OR?=?1.36, 95 % CI 1.09–1.69, P?=?0.006; TT versus CT/CC: OR?=?1.37, 95 % CI 1.05–1.80, P?=?0.022). Subgroup analysis by ethnicity showed that the association was obvious in both Caucasians and Asians. Therefore, the meta-analysis provides strong evidence for the association between NQO1 C609T polymorphism and colorectal cancer risk, and the T allele of NQO1 C609T polymorphism is an important risk factor of colorectal cancer.     

NQO1基因C6O9T多态性和环境因素与乳腺癌遗传易感性的关系

目的 探讨醌氧化还原酶1 (quinone oxido-reductase 1,NQO1)基因C609T多态性和环境因素与乳腺癌遗传易感性的关系.方法 采用以医院为基础的病例对照研究收集桂林医学院附属医院2012-10-15-2014-02-15共248例女性乳腺癌患者和该院2013-03-01-2013-12-30共284名女性健康体检者的人口学和环境暴露资料等,并采用TaqManMGB荧光定量聚合酶链反应技术和多因素非条件Logistic回归模型分析NQO1基因C609T在两组中分布频率的差异,以及与环境因素的交互作用.结果 病例组NQO1基因位点CC、CT和TT各基因型频率分别为27.42％、49.60％和22.98％,对照组中基因型频率分别为34.51％、50.35％和15.14％,差异有统计学意义,x2 =6.48,P=0.039.多因素Logistic回归分析表明,与CC基因型相比,CT或TT基因型的个体罹患乳腺癌的风险OR值分别为1.33和2.92.病例组等位基因T频率(47.78％)较对照组(40.32％)增高(x2=6.00,P=0.014),携带T等位基因者患乳腺癌的危险性是C等位基因携带者的1.36倍.交互作用分析表明,NQO1基因C609T多态性与经常熬夜、被动吸烟、精神创伤、睡觉佩戴胸罩、性格和体育锻炼等之间均存在交互作用(P＜0.05),其OR值分别为2.45、3.96、2.40、1.98、0.33和0.52.结论 NQO1基因C609T多态性可能为乳腺癌发病的遗传易感因素,且与环境因素具有协同致癌作用.     

DNA repair gene polymorphisms and tobacco smoking in the risk for colorectal adenomas

DNA damage is thought to play a critical role in the development of colorectal adenoma. Variation in DNA repair genes may alter their capacity to correct endogenous and exogenous DNA damage. We explored the association between common single-nucleotide polymorphisms (SNPs) in DNA repair genes and adenoma risk with a case-control study nested in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 1338 left sided, advanced colorectal adenoma cases and 1503 matched controls free of left-sided polyps were included in the study. Using DNA extracted from blood, 3144 tag SNPs in 149 DNA repair genes were successfully genotyped. Among Caucasians, 30 SNPs were associated with adenoma risk at P < 0.01, with four SNPs remaining significant after gene-based adjustment for multiple testing. The most significant finding was for a non-synonymous SNP (rs9350) in Exonuclease-1 (EXO1) [odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.11-1.51, P = 0.001)], which was predicted to be damaging using bioinformatics methods. However, the association was limited to smokers with a strong risk for current smokers (OR = 2.15, 95% CI = 1.27-3.65) and an intermediate risk for former smokers (OR = 1.45, 95% CI = 1.14-1.82) and no association for never smokers (OR = 0.98, 95% CI = 0.76-1.25) (P(interaction) = 0.002). Among the top findings, an SNP (rs17503908) in ataxia telangiectasia mutated (ATM) was inversely related to adenoma risk (OR = 0.75, 95% CI = 0.63-0.91). The association was restricted to never smokers (OR = 0.55, 95% CI = 0.40-0.76) with no increased risk observed among smokers (OR = 0.89, 95% CI = 0.70-1.13) (P(interaction) = 0.006). This large comprehensive study, which evaluated all presently known DNA repair genes, suggests that polymorphisms in EXO1 and ATM may be associated with risk for advanced colorectal adenoma with the associations modified by tobacco-smoking status.     

The NQO1 C609T polymorphism and risk of lung cancer: a meta-analysis

Objective: NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into hydroquinones. A single base substitution (CgT) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Published data on the association between NQO1 C609T polymorphism and lung cancer risk are conflicting. Methods: To derive a more precise estimation of the relationship, a meta-analysis was performed. Results: A total of 23 studies including 5,575 cases and 9,132 controls were assessed. The pooled result showed that the NQO1 polymorphism was not associated with a clear increased risk of lung cancer (OR = 1.009, 95% CI: 0.943-1.078; P heterogeneity=0.049). In the subgroup analysis by ethnicity, no clear increased risk was found among Asians for TT/CT versus CC (OR = 1.005; 95% CI = 0.890-1.135; Pheterogeneity=0.024). However, the TT and CT genotypes combined were associated with significantly increased risk of lung cancer in Chinese (OR = 1.237, 95% CI: 1.029-1.486; Pheterogeneity=0.061) among whom the variant allele is common. The variant genotype of NQO1 was also associated with modestly increased risk of lung cancer among white populations (OR = 1.017, 95% CI: 0.936-1.105; Pheterogeneity=0.101). However, no significant association was found in Africans with all genetic models. Conclusions: Our meta-analysis suggests that the variant NQO1 C609T genotype may affect individual susceptibility to lung cancer. This meta- analysis suggests that the NQO1 609T allele is a low penetrant risk factor for developing lung cancer in Chinese.     

NQO1 C609T polymorphism is associated with esophageal cancer risk among Chinese: a meta-analysis

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphism has been reported to influence the risk for esophageal cancer (EC) in many studies; however, the results remain controversial and ambiguous. We therefore carried out a meta-analysis of published case–control studies to investigate the association between NQO1 C609T polymorphism and EC susceptibility. Electronic searches were conducted on links between this variant and EC in several databases. Odds ratios (ORs) and 95 % confidence intervals (CIs) for homozygous, dominant model, recessive model and allele were calculated to estimate the strength of associations in fixed and random effect models. Heterogeneity and publication bias were also assessed. A total of 11 case–control studies were identified, including1,619 cases and 2,101 controls. C allele was associated with a decreased susceptibility risk of EC compared with the T allele among Chinese (OR?=?0.70; 95 % CI?=?0.59–0.84). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. Our pooled data suggest a significant association exists between NQO1 C609T polymorphism and EC among Chinese.     

Lack of association of EPHX1 gene polymorphisms with risk of hepatocellular carcinoma: a meta-analysis

Previous studies have focused on the association of a gene (EPHX1) encoding microsomal epoxide hydrolase with the carcinogenesis of hepatocellular carcinoma (HCC). In the present study, we performed a meta-analysis to systematically summarize the possible association between EPHX1 genetic polymorphisms and the risk for HCC. We conducted a search of case–control studies on the associations of EPHX1 genetic polymorphisms with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Wanfang database in China, and the Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with EPHX1 genetic polymorphism was estimated by pooled odds ratios and 95 % confidence intervals. Thirteen studies were included in the present meta-analysis. Our results showed that, for the two polymorphisms (337 T?>?C and 416A?>?G) of EPHX1 gene, neither allele frequency nor genotype distributions were associated with risk for HCC in all genetic models (all P?>?0.05). This meta-analysis suggests that EPHX1 genetic polymorphisms were not associated with the risk of HCC.     

Association between the NQO1 C609T Polymorphism with Hepatocellular Carcinoma Risk in the Chinese Population

Background: Associations between the NQO1 C609T polymorphism and hepatocellular carcinoma (HCC)risk are a subject of debate. We therefore performed the present meta-analysis to evaluate links with HCCsusceptibility. Materials and Methods: Several major databases (PubMed, EBSCO), the Chinese nationalknowledge infrastructure (CNKI) and the Wanfang database were searched for eligible studies. Crude odds ratios(ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. Results: A total of4 studies including 1,325 patients and 1,367 controls were identified. There was a significant association betweenNQO1 C609T polymorphism and HCC for all genetic models (allelic model: OR=1.45, 95%CI=1.23-1.72, p<0.01;additive model: OR=1.96, 95%CI=1.57-2.43, p<0.01; dominant model: OR=1.62, 95%CI=1.38-1.91, p<0.01; andrecessive model: OR=1.53, 95%CI=1.26-1.84, p<0.01). On subgroup analysis, similarly results were identified inAsians. For Asians, the combined ORs and 95% CIs were (allelic model: OR=1.50, 95%CI=1.24-1.82, p<0.01;additive model: OR=2.11, 95%CI=1.48-3.01, p<0.01; dominant model: OR=1.69, 95%CI=1.42-2.02, p<0.01;and recessive model: OR=1.59, 95%CI=1.16-2.19, p<0.01). Conclusions: The current meta-analysis suggestedthat the NQO1 C609T polymorphism could be a risk factor for developing HCC, particularly in the Chinesepopulation.     

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.     

Association between NQO1 C609T polymorphism and bladder cancer susceptibility: a systemic review and meta-analysis

There is growing evidence for the important roles of genetic factors in the host’s susceptibility to bladder cancer. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones. Since the NQO1 C609T polymorphism is linked to enzymatic activity of NQO1, it has also been hypothesized that NQO1 C609T polymorphism may affect the host’s susceptibility to bladder cancer by modifying the exposure to carcinogens. There were many studies carried out to assess the association between NQO1 C609T polymorphism and bladder cancer risk, but they reported contradictory results. We conducted a meta-analysis to examine the hypotheses that the NQO1 C609T polymorphism modifies the risk of bladder cancer. Eleven case–control studies with 2,937 bladder cancer cases and 3,008 controls were included in the meta-analysis. Overall, there was no obvious association between NQO1 C609T polymorphism and bladder cancer susceptibility (for T versus C: odds ratio (OR) = 1.12, 95 % confidence interval (95 %CI) 0.99–1.26, P _OR = 0.069; for TT versus CC: OR = 1.31, 95 %CI 0.95–1.81, P _OR = 0.100; for TT/CT versus CC: OR = 1.06, 95 %CI 0.95–1.18, P _OR = 0.304; for TT versus CT/CC: OR = 1.29, 95 %CI 0.94–1.77, P _OR = 0.112). After adjusting for heterogeneity, meta-analysis of those left 10 studies showed that there was an obvious association between NQO1 C609T polymorphism and bladder cancer susceptibility (for T versus C: OR = 1.18, 95 %CI 1.06–1.31, P _OR = 0.003; for TT versus CC: OR = 1.47, 95 %CI 1.14–1.90, P _OR = 0.003; for TT/CT versus CC: OR = 1.16, 95 %CI 1.01–1.34, P _OR = 0.036; for TT versus CT/CC: OR = 1.39, 95 %CI 1.10–1.75, P _OR = 0.006). There was low risk of publication bias. Therefore, our meta-analysis suggests that NQO1 C609T polymorphism is associated with bladder cancer susceptibility.     

NQO1 C609T polymorphism correlated to colon cancer risk in farmers from western region of Inner Mongolia

Objective:To investigate the relationship between NAD(P)H:quinone oxidoreductase 1(NQO1) C609T polymorphism and colon cancer risk in farmers from western region of Inner Mongolia.Methods:Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was performed to analyze NQO1 C609T polymorphism from 160 healthy controls and 76 colon cancer patients.Results:Among the colon cancer patients,the incidence of NQO1 T allele(53.29%) was significantly higher than it in control group(33.75%,P<0.001).The individuals with NQO1 T allele had higher risk [2.239(95% CI:1.510-3.321) times] to develop colon cancer than individuals with NQO1 C allele.The incidence of NQO1(T/T)(34.21%) in colon cancer patients was higher than that in control group(15.62%,P<0.001).Odds ratios(OR) analysis suggested that NQO1(T/T) and NQO1(T/C) genotype carriers had 3.813(95% CI:1.836-7.920) times and 2.080(1.026-4.219) times risk compared with wild-type NQO1(C/C) gene carriers in developing colon cancer.Individuals with NQO1(T/T) genotype had 2.541(95% CI:0.990-6.552) times,3.713(95% CI:1.542-8.935) times,and 3.471(95% CI:1.356-8.886) times risk than individuals with NQO1(T/C) or NQO1(C/C) genotype in welldifferentiated,moderately-differentiated,and poorly-differentiated colon cancer patients,respectively.Conclusions:NQO1 gene C609T could be one of risk factors of colon cancer in farmers from western region of Inner Mongolia.     

GSTT1 and GSTM1 Deletions,NQO1 C609T Polymorphism and Risk of Chronic Myelogenous Leukemia in Japanese

We conducted a prevalent case-control study with 51 chronic myelogenous leukemia (CML) cases and 476 controls ‍to investigate the associations between glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1 (GSTM1) ‍deletions, and the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism with risk of chronic myelocytic ‍leukemia in Japanese. For the GSTT1 deletion, when the GSTT1 positive genotype was defined as the reference, the ‍OR for the GSTT1 deletion genotype was 1.32 (95%CI; 0.74-2.36). For the GSTM1 deletion, when the GSTM1 ‍positive genotype was defined as the reference, the OR for the GSTM1 deletion genotype was 0.95 (95%CI; 0.53- ‍1.69). For NQO1 C609T polymorphism, when the NQO1 609CC genotype was defined as the reference, the ORs for ‍the CT genotype, TT genotype, and CT and TT genotypes combined together were 2.37 (95%CI, 1.21-4.67, P=0.012), ‍1.44 (0.55-3.74, P=0.012) and 2.12 (1.10-4.08, P=0.025), respectively. The present study revealed that the risk of CML ‍was modulated little by GSTT1 and GSTM1 deletions, but a statistically significant association between NQO1 C609T ‍polymorphism and CML was observed for Japanese. Incidence case-control studies with a larger statistical power ‍are now required to confirm our findings.     

The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis

Background:

Evidence is increasingly emerging about multiple roles for the NAD(P)H quinone oxidoreductase 1 enzyme in cancer. The C609T (rs1800566, Pro187Ser) null polymorphism of the NQO1 gene contributes significantly to the variation in enzymatic activity across different populations. NQO1 C609T polymorphism was thoroughly investigated with respect to cancer susceptibility. The results were inconsistent partly due to low sample sizes. The aim of the present work was to perform a meta-analysis to assess association for all common cancer sites separately and in combination.

Methods:

Our meta-analysis involved 92 studies including 21 178 cases and 25 157 controls. Statistical analysis involved individual cancer sites and the combined cancer risk. Association was tested under different genetic models.

Results:

We found a statistically significant association between the variant T allele and overall cancer risk in the worldwide population (for the TT vs CC model, OR=1.18 (1.07–1.31), P=0.002, I²=36%). Stratified analysis revealed that this association was largely attributed to the Caucasian ethnicity (for the TT vs CC model, OR=1.28 (1.12–1.46), P=0.0002, I²=1%). Stratification by tumour site showed significant association for bladder cancer in the worldwide population (for the TT vs CC model, OR=1.70 (1.17–2.46), P=0.005, I²=0%), and in the Asian population (for the TT vs CC model, 1.48 (1.14–1.93), P=0.003, I²=16%). Positive association was also found for gastric cancer in the worldwide population under the dominant model (OR=1.34 (1.09–1.65), P=0.006, I²=15%).

Conclusion:

Our results indicate that the C609T polymorphism of the NQO1 gene is an important genetic risk factor in cancer.     

Lack of association of NQO1 and GSTP1 polymorphisms with multiple myeloma risk

Individual differences in xenobiotica metabolising capacity can influence susceptibility to multiple myeloma. NQO1 and GSTT1 polymorphisms were recently reported as risk factors for multiple myeloma and GSTP1 genotype was found to be a prognostic marker for therapy outcome in multiple myeloma. The aim of this study was to determine whether specific defective alleles of NQO1 (P187S) and GSTP1 (I105V) genes are associated with increased risk of multiple myeloma. Individual genotypes of 128 patients affected by multiple myeloma and 245 healthy controls were determined and our results do not support any major role of NQO1 or GSTP1 polymorphisms in multiple myeloma pathogenesis.     

聚合酶链式反应-单链构象多态性分析法检测大肠腺瘤及大肠癌APC基因突变

目的对１５例散发性大肠腺瘤组织和４５例大肠癌组织及其各自的正常肠粘膜组织，进行家族性腺瘤息肉病基因（ａｄｅｎｏｍａｔｏｕｓｐｏｌｙｐｏｓｉｓｃｏｌｉ，ＡＰＣ）第１５外显子ＭＣＲ区域的基因突变检测。方法应用聚合酶链式反应单链构象多态性分析（ＰＣＲＳＳＣＰ）技术进行检测。结果在散发性大肠腺瘤组织中检出突变率为２０．０％（３／１５），在大肠癌组织中的突变率为２２．２％（１０／４５）。实验结果表明，ＡＰＣ基因在散发性大肠腺瘤与大肠癌中均有较高突变频率，两者差异无显著性；ＡＰＣ基因突变在大肠癌中与肿瘤的大小、位置、组织分化程度和有无淋巴结转移无关；ＡＰＣ基因第１５外显子的ＭＣＲ区域是该基因突变的集中区域，且以１３３９～１４３６密码子区域突变率最高，１２６０～１３５９密码子区域突变率最低。结论证实了ＡＰＣ基因突变发生于腺瘤形成阶段，属于大肠癌发生的早期事件。     

聚合酶链式反应—单链构象多态性分析法检测大肠腺瘤及大肠癌APC …

目的 对１５例散发性大肠腺瘤组织和４５例大肠癌组织及各自的正常肠粘膜组织,进行家族性腺瘤肉病基因（ａｄｅｎｏｍａｔｏｕｓｐｏｌｙｐｏｓｉｓ,ｃｏｌｉ,ＡＰＣ第１５外显子ＭＣＲ区域的基因突变检测。方法 应用聚合酶链反应－单链构象多态性分析（ＰＣＲ－ＳＳＣＰ）技术进行检测。结果 在散发性大肠腺瘤组织中检出突变率为２０．０％（３／１５）在大肠癌组织中的突变率为２２．２％（１０／４５）。实验结果表明,ＡＰ     

Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas

Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1) to S-phase cell cycle transition, promoting cell proliferation. A recently described codon 242, exon 4, G to A single nucleotide polymorphism (A870G) produces a longer half-life cyclin D1. To investigate whether CCND1 genotype influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161 incident sporadic adenoma cases and 213 controls ages 30-74 years in a North Carolina colonoscopy-based case-control study. At least one polymorphic A allele was found in 68% of cases and 60% of controls. Having an A allele was associated with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was 1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for those whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm; OR 2.4, 95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1-3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0). Joint risk factor multivariate analyses revealed stronger positive associations among those who were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8, 95% CI 1.3-5.7), currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank alcohol (OR 2.2, 95% CI 1.2-4.2) if they had an A allele and stronger inverse associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2-0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they had no A allele. These data support the hypothesis that the CCND1 A870G polymorphism may increase risk for colorectal neoplasms.     

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and lung cancer risk: a meta-analysis

No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis to summarize the possible association. We conducted a computer retrieval of PubMed and Embase databases prior to May 2013. References of retrieved articles were also screened. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. According to the inclusion criteria, 25 articles (32 studies) were finally included. There was no statistical association between C609T polymorphism and lung cancer risk in overall, East Asians, African Americans, or Hispanics. In Caucasians, a significant association was found in allele comparison model (T vs. C) (P?=?0.04, OR?=?1.09, 95% CI 1.00–1.19, P _{heterogeneity}?=?0.24, fixed-effects model). In the subgroup of squamous cell carcinoma, a borderline significance could be found in the dominant genetic model (TT?+?CT vs. CC) (P?=?0.05, OR?=?1.20, 95% CI 1.00–1.43, P _{heterogeneity}?=?0.65, fixed-effects model). Significant association could also be found in allele comparison (T vs. C) (P?=?0.03, OR?=?1.21, 95% CI 1.01–1.44, P _{heterogeneity}?=?0.68, fixed-effects model). In the subgroup of small cell lung cancer risk, significant association were found in allele comparison (T vs. C) (P?=?0.03, OR?=?1.68, 95%CI 1.05–2.68, P _{heterogeneity}?=?0.10, random-effects model) and in the homozygote comparison (TT vs. CC) (P?=?0.02, OR?=?2.79, 95% CI 1.14–6.85, P _{heterogeneity}?=?0.72, fixed-effects model). No association was observed in adenocarcinoma subgroup. Our study suggested that NQO1 C609T polymorphism might associate with lung cancer risk in Caucasians. This polymorphism might also associate with squamous cell carcinoma and small cell lung cancer risk.     

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of eight cancers for Japanese

Methods. The cases were 102 patients with esophageal cancer, 143 with stomach cancer, 74 with colon cancer, 72 with rectal cancer, 192 with lung cancer, 237 with breast cancer, 56 with prostate cancer, and 108 with malignant lymphoma. Controls consisted of outpatients from two sources: 241 noncancer outpatients who underwent gastroscopy and 399 first-visit outpatients, expected to include about 20% with cancer. Genotyping was conducted by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Results. The TT genotype with null enzyme activity was found in 19.9% of the 241 noncancer gastroscopy examinees, 16.5% of the 399 first-visit outpatients, 12.7% of the esophageal cancer patients, 16.8% of the stomach cancer patients, 13.5% of the colon cancer patients, 9.7% of the rectal cancer patients, 17.7% of the lung cancer patients, 14.3% of the breast cancer patients, 16.1% of the prostate cancer patients, and 15.7% of the malignant lymphoma patients. The odds ratios (ORs) of the genotypes were not significant for any cancers combined or for any site of cancer, except for lung cancer (OR, 0.66; 95% confidence interval [CI], 0.46–0.96 for CT relative to CC). The OR of current smoking for cancers of the esophagus and lung combined was different between the CC genotype (OR, 2.06; 95% CI, 1.06–3.98) and TT genotype (OR, 5.11; 95% CI, 1.37–19.05), although the difference was not significant. Conclusion. This study suggests that the CC genotype of the NQO1 C609T polymorphism is associated with the risk of lung cancer, and that the TT genotype increases the risk of smoking for cancers of the esophagus and lung. Received: October 15, 2001 / Accepted: January 30, 2002