The NAD(P)H: Quinine Oxidoreductase 1 (NQO1) Gene 609 C>T Polymorphism is Associated with Gastric Cancer Risk: Evidence from a Case-control Study and a Meta-analysis

The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism(rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We firstconducted a case-control study to assess this association in a large Han Chinese population, and then performeda meta-analysis to further address this issue. Although our case-control association study indicated no significantdifference in the genotype and allele distributions of C609T polymorphism between gastric cancer patientsand controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated asignificantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84),dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratifiedanalysis by study design demonstrated stronger associations in population-based than in hospital-based studies.And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 geneC609T polymorphism increases the risk for gastric cancer, especially in Asian populations.     

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.     

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     

Targeting NAD(P)H:Quinone Oxidoreductase (NQO1) in Pancreatic Cancer

NAD(P)H:Quinone oxidoreductase (NQO1) functions as an important part of cellular antioxidant defense by detoxifying quinones, thus preventing the formation of reactive oxygen species. The aims of our study were to determine if NQO1 is elevated in pancreatic cancer specimens and pancreatic cancer cell lines and if so, would compounds previously demonstrated to redox cycle with NQO1 be effective in killing pancreatic cancer cells. Immunohistochemistry of resected pancreatic specimens demonstrated an increased immunoreactivity for NQO1 in pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) specimens versus normal human pancreas. Immunocytochemistry and Western immunoblots demonstrated inceased immunoreactivity in pancreatic cancer cells when compared to a near normal immortalized human pancreatic ductal epithelial cell line and a colonic epithelial cell line. Streptonigrin, a compound known to cause redox cycling in the presence of NQO1, decreased clonogenic survival and decreased anchorage‐independent growth in soft agar. Streptonigrin had little effect on cell lines with absent or reduced levels of NQO1. The effects of streptonigrin were reversed in pancreatic cancer cells pretreated with dicumarol, a known inhibitor of NQO1. NQO1 may be a therapeutic target in pancreatic cancer where survival is measured in months. © 2006 Wiley‐Liss, Inc.     

No Association of NAD(P)H: quinone oxidoreductase 1 (NQO1)C609T Polymorphism and Risk of Hepatocellular CarcinomaDevelopment in Turkish Subjects

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reductionof numerous quinoid compounds into their less toxic form, thus NQO1 protecting cells against oxidative stress.The gene coding for NQO1 has a single nucleotide polymorphism (C→T) at nucleotide position 609 (prolineto serine substitution at position 187 in amino acid sequence (P187S)) (rs1800566) of the NQO1 cDNA whichresults in very low enzimatic activity, so it would be expected that individuals with the homologous NQO1C609T polymorphism would have a susceptibility developing cancer. Previous studies of the association betweenfunctional NQO1 C609T polymorphism and several human cancers have had mixed findings but associationof NQO1 C609T polymorphism with hepatocellular carcinoma (HCC) development has yet to be investigated.In this study, we aim to evaluate the the association of NQO1 C609T with the risk of hepatocellular carcinoma(HCC) development among Turkish population. NQO1 C609T polymorphism was investigated in 167 confirmedsubjects with HCC and 167 cancer-free control subjects matched on age, gender, smoking and alcohol consumptionby using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. Thereis no association between the allel or genotype of NQO1 C609T polymorphism and HCC development riskin the Turkish subjects examined (p>0.05). Our result demonstrate for the first time that the NQO1 C609Tpolymorphism is not a genetic susceptibility factor for HCC in the Turkish population. Independent studies areneed to validate our findings in a larger series, as well as in patients of different ethnic origins.     

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.     

Cyclooxygenase-2 Promoter 765C Increase of Digestive Tract Cancer Risk in the Chinese Population: a Meta-analysis

Background: To evaluate relationship between the cyclooxygenase-2 promoter 765G/C polymorphism anddigestive cancer risk in China. Materials and Methods: A literature search through February 2014 was performedusing PubMed, Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure(CNKI) databases, and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs.Results: In total, 9 articles with 3,263 cases and 4,858 controls were included in this meta-analysis.The pooled OR(95%CIs) in the co-dominant model (GC vs GG) was 1.56 [1.19, 2.06], and in the dominant model ((CC+GC) vsGG), the pooled OR was 1.59 [1.21, 2.09] in overall cancers. In the subgroup analysis, stratified by cancer type,significant associations were found that the-765C allele had increased pancreatic cancer and gastric risk. Nosignificant liver cancer and colorectal cancer risk of COX-2 -765G/C polymorphism was found. Conclusions: Thesefindings suggest that COX-2-765*C is related to cancer susceptibility and may increase gastric and pancreaticcancer risk.     

NQO1基因多态性与大肠癌遗传易感性

目的:探讨依赖还原型辅酶Ⅰ/Ⅱ:醌氧化还原酶(NQO1)基因多态性与大肠癌遗传易感性之间的相关性.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)基因型分析技术对101例大肠癌患者及103例对照者NQO1 cDNA 609位点多态性进行测定.结果:基因型频率分布在大肠癌组与对照组差异显著(X2=9.52,P＜0.01),T/T基因型携带者大肠癌患病危险性是野生纯合型(C/C)的3.56倍(OR=3.56,95%CI为1.58～7.96).NQO1 T等位基因及C等位基因频率在大肠癌组与对照组分别为42.1%、57.3%,57.9%、42.7%,T等位基因频率两组有显著差异(X2=9.43,P＜0.01),T等位基因携带者患大肠癌的危险性是C等位基因携带者的1.85倍,(OR=1.85,95%CI为1.25～2.73).结论:NQO1在大肠癌的形成过程中起一定的保护作用,而NQO1 cDNA 609位点T等位基因可能是大肠癌发生的危险因素,NQO1基因的多态性与生活特征共同决定个体大肠癌的患病风险.     

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

Objective: The NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 polymorphism, leading to prolinetoserineamino-acid and enzyme activity changes, has been implicated in bladder cancer risk, but individuallypublished studies showed inconsistent results. We therefore here conducted a meta-analysis to summarize thepossible association. Methods: A systematic literature search up to August 27, 2012 was carried out in PubMed,EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios (ORs)with 95% confidence intervals (CIs) were analyzed for homozygote contrast (TT vs. CC), additive model (T vs.C), dominant model (TT+CT vs. CC), and recessive model (TT vs. CC+CT) to assess the association using fixedorrandom-effect models. Results: We identified 12 case-control studies including 3,041 cases and 3,128 controlsfor the present meta-analysis. Significant association between NQO1 rs1800566 genetic polymorphism and riskof bladder cancer was observed in the additive model (OR = 1.15, 95% CI = 1.01-1.30, p = 0.030). Moreover, inthe subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 1.26, 95%CI = 1.08–1.47, p = 0.003 for T vs. C; OR = 1.68, 95% CI = 1.21-2.32, p = 0.002 for TT vs. CC; OR = 1.50, 95%CI = 1.13-1.98, p = 0.005 for TT vs. CT+CC) but not in Caucasians. Conclusions: The results suggest that NQO1rs1800566 genetic polymorphism may contribute to bladder cancer development, especially in Asians.     

Effects of the NQO1 609C>T Polymorphism on Leukemia Susceptibility: Evidence from a Meta-analysis

A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serineamino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually publishedinvestigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a metaanalysisof 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized thedata on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroupanalyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associatedwith a modestly increased risk of leukemia (TT versus CT/CC: OR = 1.23, 95%CI = 1.00 - 1.51, heterogeneity= 0.76; I2 = 0%). Following further stratified analyses, increased risk was only observed in subgroups ofCaucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemiain Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small samplesizes of the subgroup analyses suggest that further larger studies are needed.     

Association between Helicobacter pylori seropositivity and NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism observed in outpatients and health checkup examinees

Background Significant associations of Helicobacter pylori (H. pylori) seropositivity have been found with several host polymorphisms. This study investigated the associations of functional polymorphisms of the NQO1, GSTM1, and GSTT1 genes of detoxification enzymes, with the seropositivity, as well as with pepsinogen levels, as markers of gastric atrophy.Methods The subjects were 241 noncancer outpatients who had participated in an H. pylori eradication program (HPE) at Aichi Cancer Center Hospital, and 465 health checkup examinees in Nagoya (HCE). The NQO1 C609T, GSTM1, and GSTT1 polymorphisms were determined by triplex polymerase chain reaction with confronting two-pair primers (PCR-CTPP).Results The sex- and age-group-adjusted odds ratio (OR) of NQO1 C/C for H. pylori seropositivity relative to T/T was highly significant; OR, 1.92; 95% confidence interval (95% CI), 1.22–3.03. The ORs of the GSTM1 present type and GSTT1 present type for H. pylori seropositivity were not significant; OR, 0.87; 95% CI, 0.64–1.20 and OR, 1.14; 95% CI, 0.83–1.57, respectively. The association of the NQO1 C/C genotype with H. pylori seropositivity was observed only for never-smokers; OR, 2.25; 95% CI, 1.33–3.79. The genotypes of the NQO1, GSTM1, and GSTT1 genes were not associated with the development of atrophic gastritis among the H. pylori-seropositive subjects.Conclusion This is the first study to report a significant association of the NQO1 C609T polymorphism with H. pylori seropositivity. The biological mechanism explaining the significant association with the seropositivity remains to be elucidated.     

Association Between the (GT)n Polymorphism of the HO-1 Gene Promoter Region and Cancer Risk: a Meta-analysis

Background: Several studies have previously focused on associations between the (GT)n repeat polymorphismof the heme oxygenase-1 (HO-1) gene promoter region and risk of cancers, but results are complex. We conductedthe present meta-analysis to integrate relevant findings and evaluate the association between HO-1 (GT)nrepeat polymorphism and cancer susceptibility. Materials and Methods: Published literature was retrievedfrom the PubMed/MEDLINE, EMBASE and ISI Web of Science databases before November 2013. For allalleles and genotypes, odds ratios were pooled to assess the strength of the associations using either fixed-effectsor random-effects models according to heterogeneity. Subgroup analysis was conducted according to ethnicityand histopathology. Results: A total of 10 studies involving 2,367 cases and 2,870 controls were identified. Theresults showed there was no association between HO-1 (GT)n repeat polymorphism and the cancer risk both atthe allelic and genotypic level. However, in the stratified analysis, we observed an increased risk of squamouscell carcinoma in persons carrying the LL genotype and the LL+LS genotype as compared with those carryingthe SS genotype. When the LS and SS genotypes were combined, the odds ratio for squamous cell carcinoma inLL-genotype carriers, were also significantly increased. No publication bias was observed. Conclusions: The LLgenotype and L-allele carrying genotypes (LL+LS) of HO-1 (GT)n repeat polymorphism are potential geneticfactors for developing squamous cell carcinoma. More large and well-designed studies are required for furthervalidations.     

NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser Polymorphism and Colorectal Cancer Predisposition in the Ethnic Kashmiri Population

The C609T single nucleotide polymorphism of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene hasbeen identified as an important risk parameter for the susceptibility to colorectal cancer. We here carried out acase-control study and examined the genotype distribution of NQO1 C609T (Pro189Ser) using the polymerasechain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, to investigate the possiblerole of this SNP as a risk factor in colorectal cancer development in Kasmir, India. We investigated the genotypedistribution in 86 CRC cases in comparison with 160 healthy subjects and also focused on clinicopathologicalvariables in the CRC cases. The observed genotype frequencies in cases and controls were significantly different[OR=1.64; 95%CI=0.94-2.86]. We also found a significant association between the Ser/Ser variant form withage group, smoking status, tumor location, nodal status/ higher tumor grade and with exposure to pesticides.Therefore, we suggest that the NQO1 C609T SNP is involved either in susceptibility or development of CRC inthe ethnic Kashmiri population.     

No Association Between the CYP1B1 C4326G Polymorphism and Endometrial Cancer Risk: a Meta-analysis

Purpose: Any association between the CYP1B1 C4326G polymorphism and endometrial cancer risk remains inconclusive. In order to provide a more precise estimate, we performed the present meta-analysis. Methods: We used fixed effect or random effect models to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs) for endometrial cancer risk, with the Chi-square-based Q-test used to test for heterogeneity. Begg’s and Egger’s tests were adopted to check publication bias. Results: Six published case-control studies of association between the CYP1B1 C4326G polymorphism and endometrial cancer risk covering 6,577 subjects were included in the meta-analysis, but the results indicated no significant correlation with allele contrast and genotype comparisons (G vs C: OR 1.01, 95% CI 0.93-1.09; GG vs CC: OR 1.04, 95% CI 0.88-1.23; CG + GG vs CC: OR 1.08, 95% CI 0.97-1.21; GG vs CC + CG: OR 1.01, 95% CI 0.87-1.17). Heterogeneity hypothesis test did not reveal any heterogeneity and Begg’s and Egger’s tests did not detect obvious publication bias. Conclusions: There is no association between the CYP1B1 C4326G polymorphism and endometrial cancer risk.     

Association Between GSTM1 Polymorphism and Nasopharyngeal Cancer Susceptibility: a Meta-analysis

Background/Aims: Glutathione S-transferase M1 (GSTM1) is a multifunctional enzyme that plays a criticalrole in the detoxification of varieties of carcinogenic metabolites. Many studies have been conducted to investigatethe association between GSTM1 polymorphism and nasopharyngeal cancer (NPC) risk, but the findings amongthose studies are inconsistent. To assess this relationship more precisely, we performed a meta-analysis of allavailable studies on the subject. Methods: Case-control studies were identified by searching Pubmed, Embase,ISI Web of Science, and Wanfang databases through September 6, 2012. We used the pooled odds ratio (OR)with its corresponding 95% confidence interval (95%CI) to evaluate the association of GSTM1 polymorphismwith NPC susceptibility. Subgroup analyses by pathological types, sex and smoking status were performed tofurther identify the association. Results: Overall, 11 published studies with 1,513 cases and 2,802 controls werefinally included into this meta-analysis according to the inclusion criteria. Meta-analysis of total studies showedthat the null genotype of GSTM1 was significantly associated with increased risk of NPC, when comparing withthe non-null genotype (OR=1.51, 95%CI=1.33-1.72, POR<0.001). The association was still statistically significantin subgroup analysis of patients with nasopharyngeal squamous cell carcinoma (OR=1.73, 95%CI=1.24-2.42,POR=0.001). Males with the null genotype of GSTM1 were more likely to subject to NPC than females. Inaddition, the association between the null genotype of GSTM1 and NPC risk was strongest in individuals withexposure to smoking. Sensitivity analysis by sequential omission of any individual studies one at a time furtherdemonstrated the significant association. Conclusions: The findings suggest that the null genotype of GSTM1 isa risk factor for NPC, and there is a gene- smoking interaction in this association     

The 2518 A/G Polymorphism in the MCP-1 Gene and Cancer Risk: A Meta-analysis

Background: The 2518 A/G polymorphism in the MCP-1 gene has been extensively studied for associationswith cancer; however, results from replication studies have been inconsistent. The aim of this investigationwas to determine links with risk of cancer by meta-analysis. Methods: We searched Pubmed, Embase, CNKI,Weipu and Wanfang databases, covering all case-control studies until March, 2013. Statistical analyses wereperformed using the Revman 5.0 software. Results: A total of 11 case-control studies met our inclusion criteria,including 1,422 cases and 2,237 controls. The results indicated that the MCP-1 2518 gene polymorphism had noassociation with cancer risk overall (GG vs.GA+ AA: OR = 0.89, 95%CI = 0.61–1.28, P = 0.52). However, in thesubgroup analysis by ethnicity, a decrease of cancer risk was found in Asian populations (GG vs.GA+ AA: OR =0.79, 95%CI = 0.63–0.99, P = 0.04). Conclusion: This meta-analysis suggested that the 2518A/G polymorphismof MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations.     

Association between NAD(P)H: quinone oxidoreductase 1 (NQ01) inactivating C609T polymorphism and adenocarcinoma of the upper gastrointestinal tract

NQO1 is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single nucleotide polymorphism (C-->T) at position 609 of the NQO1 cDNA has been associated with susceptibility to tumours induced by chemical carcinogens. In our case-control study, we determined the prevalence of the C609T NQO1 polymorphism by PCR-RFLP analysis in Caucasian patients with oesophageal adenocarcinoma (OAC; n=61), cardiac adenocarcinoma (CAC; n=120) or gastric adenocarcinoma (GAC; n=203) vs. a control group that consisted of 252 healthy blood donors. Additionally, NQO1 mRNA expression and NQO1 protein expression were determined by RT-PCR and immunohistochemistry in a subset of cases. The NQO1 C609T genotype distribution was significantly different among controls (C/C, 73.4%; C/T, 25.0%; T/T, 1.6%) as compared to OAC patients (C/C, 49.2%; C/T, 47.5%; T/T, 3.3%; p=0.0004), CAC patients (C/C, 55.8%; C/T, 40.0%; T/T, 4.2%; p=0.0005) and with GAC patients (C/C, 65.5%; C/T; 30.6%, T/T; 3.9%; p=0.0377). The 609T allele overall frequency was 0.141 in controls, 0.270 in OAC patients, 0.241 in CAC patients and 0.192 in GAC patients. Individuals carrying 1 or 2 609T alleles had a 2.85-fold higher risk (95% CI: 1.61-5.07; p=0.0003) for the development of OAC and a 2.18-fold higher risk (95% CI: 1.38-3.44; p=0.0007) for the development of CAC than wild-type gene homozygotes. Immunohistochemical analysis showed NQO1 protein expression in 133 carcinomas, whereas 17 carcinomas were negative. Negativity for NQO1 protein expression correlated strongly with the NQO1 genotype being present in 3.9% of cases with C/C, 13.9% of cases with C/T and 62.5% of cases with T/T genotype (p<0.001). In contrast, NQO1 mRNA expression was detectable irrespective of underlying genotype. In conclusion, determination of the NQO1 genotype may gain importance as a stratification marker in future prevention trials for adenocarcinoma of upper gastrointestinal tract.     

Lack of Association Between the CYP1A1 Ile462Val Polymorphism and Endometrial Cancer Risk: a Meta-analysis

Purpose: Any association between the CYP1A1 Ile462Val polymorphism and endometrial cancer risk remainsinconclusive. For a more precise estimate, we performed the present meta-analysis. Methods: PUBMED, OVIDand EMBASE were searched for the studies which met inclusion criteria. Data in all eligible studies wereevaluated and extracted by two authors independently. The meta-analysis estimated pooled odds ratio (OR) with95% confidence interval (CI) for endometrial cancer risk attributable to the CYP1A1 Ile462Val polymorphism.Results: A total of 7 studies were included in this meta-analysis. The results indicated no association betweenendometrial cancer risk and the CYP1A1 Ile462Val polymorphism (for Val vs Ile allele model [OR 1.09, 95%CI 0.73-1.62]; for Val.Val vs Ile.Ile genotype model [OR 1.54, 95% CI 0.56-4.23]; for (Ile.Val + Val.Val) vs Ile.Ilegenotpye model [OR 1.08, 95% CI 0.71-1.63]; for Val.Val vs (Ile.Ile + Ile.Val) genotype model [OR 1.46, 95% CI0.53-4.04]). Conclusions: This meta-analysis suggests that there is no association between endometrial cancerrisk and the CYP1A1 Ile462Val polymorphism.     

Association of the PTEN IVS4 (rs3830675) Gene Polymorphism with Reduced Risk of Cancer: Evidence from a Meta-analysis

PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulatingcell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted ameta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancerin detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies publisheduntil December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidenceintervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer casesand 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysissuggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e.,allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD:OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889,p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests thatthe PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future largerstudies with other groups of populations are warranted to clarify this association.