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.     

Association of NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single base substitution (C --> T) polymorphism at nucleotide 609 (null-allele) of NQO1 gene impairs stability and function of the NQO1 protein. To investigate the association of this NQO1 polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC), the NQO1 C609T genotypes were determined by PCR-RFLP analysis in 450 patients with ESCC (257 German Caucasians and 193 northern Chinese) and 393 unrelated healthy controls (252 German Caucasians and 141 northern Chinese). Additionally, NQO1 protein expression was determined by immunohistochemistry in a subset of 74 ESCC (50 German, 24 Chinese). A significant difference in NQO1 C609T genotype distribution was observed between Caucasian healthy controls (C/C, 73.4%; C/T, 25.0%; T/T, 1.6%) and Chinese healthy controls (C/C, 34.0%; C/T, 49.7%; T/T, 16.3%) (chi(2) = 68.40, P < 0.001). The NQO1 T/T genotype significantly increased the risk for developing ESCC in both Caucasian subjects (OR = 4.62, 95% CI = 1.54-13.86) and Chinese subjects (OR = 1.81, 95% CI = 1.04-3.15), compared with the combined C/C and C/T genotypes. In Chinese subjects, this increased susceptibility was pronounced in patients with family history of upper gastrointestinal cancers (OR = 2.18, 95% CI = 1.14-4.17). Immunohistochemical analysis showed NQO1 protein expression in 53 carcinomas, whereas 21 carcinomas were negative. Negativity for NQO1 expression correlated strongly with the NQO1 genotype, being present in 8.6% of cases with C/C, 22.2% of cases with C/T and 100% of cases with T/T genotype (chi(2) = 16.60, P < 0.001). In summary, the association of the NQO1 C609T polymorphism with ESCC in genetically distinct populations makes a strong argument for its importance in carcinogenesis of ESCC in the German Caucasian and the northern Chinese population.     

Oral contraceptive use and breast cancer risk: modification by NAD(P)H:quinone oxoreductase (NQO1) genetic polymorphisms.

Despite intensive study, the relationship between oral contraception (OC) and breast cancer remains unclear. OCs contain a potent synthetic estrogen (ethinyl estradiol) but lower endogenous estradiol levels, and ethinyl estradiol is a weak progenitor of semiquinones, catechol estrogens capable of damaging DNA. NAD(P)H:quinone oxoreductase (NQO1) stabilizes semiquinones, thus potentially preventing genetic damage from catechol estrogens, and the NQO1 C609T polymorphism seems functionally relevant. Using data from the Shanghai Breast Cancer Study, a population-based case-control study, we investigated the relationships between OC use (20% ever using), breast cancer, and NQO1 (C/C 31% and C/T + T/T 69%) among 1,039 cases and 1,121 controls. Breast cancer was not significantly associated with NQO1 genotype. There was a significant protective association between OC after age 30 years and premenopausal breast cancer [odds ratio (OR) 0.51, 95% confidence interval (95% CI) 0.29-0.89] primarily with the NQO1 T allele (C/C OR 0.76, 95% CI 0.31-1.82; C/T + T/T OR 0.38, 95% CI 0.18-0.80; P for interaction = 0.19). The association between premenopausal breast cancer and OCs significantly differed with NQO1 genotype when using OCs for >18 months (C/C OR 2.34, 95% CI 0.92-5.99; C/T + T/T OR 0.69, 95% CI 0.38-1.25; P for interaction = 0.02). Among women with the C/C genotype, postmenopausal breast cancer was significantly associated with ever-using OCs (C/C OR 2.01, 95% CI 1.08-3.74; C/T + T/T OR 0.72, 95% CI 0.49-1.05; P for interaction < 0.01). This crossover was stronger with OC use prior to age 30 years (C/C OR 3.00, 95% CI 1.43-6.25; C/T or T/T OR 0.49, 95% CI 0.29-0.81; P for interaction < 0.01). Our results require confirmation but suggest that the OC and breast cancer association depends on the ability to invoke protection from catechol estrogens.     

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.     

Role of NQO1C609T and EPHX1 gene polymorphisms in the association of smoking and alcohol with sporadic distal colorectal adenomas: results from the UKFSS Study

NADP(H):quinone oxidoreductase 1 (NQO1) and microsomal epoxide hydrolase (EPHX1, also mEH) are attractive candidate enzymes for association with colorectal neoplasia because they metabolize a number of compounds including polycyclic aromatic hydrocarbons (PAHs) that have been linked with colorectal carcinogenesis. We examined the relationship between NQO1C609T, mEH3, mEH4 and risk of sporadic distal colorectal adenomas in one of the largest case-control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening (UKFSS) Trial. The polymorphisms were examined as independent risk factors and evidence for interaction with smoking and alcoholic drinks was sought. The NQO1 609*T allele was positively associated with high-risk adenoma in this population [odds ratio (OR), 1.36; 95% confidence interval (CI), 1.02-1.83]. Elevated risk estimates were seen in smokers independently of the genotype but the association was stronger among current smokers with the heterozygous variant genotype (OR, 4.24; 95% CI, 2.54-7.09). It was reported for the first time that the association between alcohol and colorectal adenoma was modified by NQO1C609T genotype, such that the relation between alcohol and colorectal adenoma was stronger among those with the common C/C genotype (OR, 1.49; 95% CI, 1.11-2.02; P-interaction = 0.024). There was no association between mEH3 and mEH4 variants and colorectal adenoma risk and no effect modification by alcohol and smoking. These findings provide evidence for an important role of the NQO1C609T polymorphism in susceptibility of colorectal adenomas. Alcohol increases risk of colorectal adenoma in carriers of the high-activity genotype possibly through enhanced activation of alcohol-related procarcinogens.     

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.     

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.     

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.     

NQO1 T allele associated with decreased risk of later age at diagnosis lung cancer among never smokers: results from a population-based study

The NAD(P)H:quinone oxidoreductase 1 gene, NQO1, contains a C to T transition at amino acid codon 187, which results in very low enzymatic activity. Previous studies of the association between NQO1 genotype and lung cancer have had mixed findings. This population-based case control study examines the association between NQO1 genotype and lung cancer in the largest sample of never smokers (<100 cigarettes, lifetime) to date. Cases (n = 161) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program, and 5-year age- and race-matched population-based controls (n = 173) were identified using random digit dialing. Allele frequencies of C and T, respectively, were 0.79 and 0.21 in Caucasians, and 0.84 and 0.16 in African Americans. Among those diagnosed aged >/=50 years, C/T and T/T genotyped individuals had 0.48 times lower lung cancer risk than individuals with C/C genotype (95% CI: 0.27-0.87). There was a non-significant suggestion of a protective effect associated with the T allele among those with a history of environmental tobacco smoke exposure (OR = 0.57, 95% CI: 0.32-1.03) but not among those without (OR = 0.98, 95% CI: 0.41-2.38). Sex, race, family history of lung cancer and histologic type did not modify the effect of NQO1 genotype on lung cancer risk. The observed risk reductions may be attributable to the greatly reduced procarcinogen activating of NAD(P)H:quinone oxidoreductase 1 in individuals with at least one copy of the T allele.     

Genetic polymorphism of NAD(P)H:quinone oxidoreductase is associated with an increased risk of infant acute lymphoblastic leukemia without MLL gene rearrangements.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.     

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.     

NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, their less toxic form. A sequence variant at position 609 (C --> T) in the NQO1 gene encodes an enzyme with reduced quinone reductase activity in vitro and thus was hypothesized to affect cancer susceptibility. We conducted meta-analyses focusing on three cancer sites (lung, bladder, and colorectum) to summarize the findings from the current literature and to explore sources of heterogeneity. RESULTS: There is no clear association between the NQO1 Pro187Ser polymorphism and lung cancer risk in the three ethnic groups examined: odds ratio (OR(White)) C/T + T/T versus C/C = 1.04 [95% confidence interval (95% CI), 0.96-1.13], OR(Asian) = 0.99 (95% CI, 0.72-1.34), and OR(Blacks) = 0.95 (95% CI, 0.66-1.36). However, a modestly increased risk was suggested for the variant homozygotes in whites (OR T/T versus C/C, 1.19; 95% CI, 0.94-1.50). Analysis excluding one outlier study suggested the variant allele may be associated with reduced lung cancer risk in Asians. Meta-analyses for bladder and colorectal cancer suggested a statistically significant association with the variant genotypes in whites. In stratified analyses, the NQO1 Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians. CONCLUSIONS: Results from our meta-analyses suggest that the variant NQO1 Pro187Ser genotype may affect individual susceptibility to lung, bladder, and colorectal cancer. Such effects of the NQO1 polymorphism seem to be modified by ethnicity and smoking status.     

NAD(P)H: Quinone Oxidoreductase 1 (NQO1) C609T Gene Polymorphism Association with Digestive Tract Cancer: A Meta-analysis

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence therisk for digestive tract cancer (DTC) in many studies; however, the results remain controversial and ambiguous.We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimationof any associations. Electronic searches were conducted on links between this variant and DTC in severaldatabases through April 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated toestimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias werealso assessed. A total of 21 case-control studies were identified, including 6,198 cases and 7,583 controls. Overall,there was a statistically significant association between the NQO1 C609T polymorphism and DTC risk (TT vs.CC: OR=1.224, 95%CI=1.055-1.421; TT/CT vs. CC: OR=1.195, 95%CI=1.073-1.330; TT vs. CT/CC: OR=1.183,95%CI=1.029-1.359; T vs. C: OR=1.180, 95%CI=1.080-1.290). When stratified for tumor location, the resultsbased on all studies showed the variant allele 609T might have a significantly increased risk of upper digest tractcancer (UGIC), but not colorectal cancer. In the subgroup analysis by ethnicity, we observed a significantly riskfor DTC in Caucasians. For esophageal and gastric cancer, a significantly risk was found in both populations,and for colorectal, a weak risk was observed in Caucasians, but not Asians. This meta-analysis suggested thatthe NQO1 C609T polymorphism may increase the risk of DTC, especially in the upper gastric tract.     

A functional NQO1 609C>T polymorphism and risk of hepatocellular carcinoma in a Chinese population

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, thus protecting cells from oxidative damage. A single base substitution (C→T) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Thus, the lack of enzymatic activity in the homozygous C609T NQO1 polymorphism (rs1800566) may play a pivotal role in tumor development. We hypothesized that a genetic variant in NQO1 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis that the variant may play a role in HCC susceptibility, we conducted a hospital-based case–control study of 476 HCC patients and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method was performed to detect the polymorphism. The results showed that the variant alleles and genotypes of NQO1 C609T were more common among cases than those among controls (P?=?0.003 and P?=?0.024). Compared with the NQO1 609CC genotype, there was a significantly greater risk of HCC associated with the variant NQO1 609TT [adjusted odds ratio (OR)?=?1.60, 95 % confidence interval (CI)?=?1.12–2.28] and combined NQO1 609TC/TT (adjusted OR?=?1.37, 95 % CI?=?1.04–1.80) genotypes. Moreover, when subgroup analyses were performed, we found that the increase in risk was more evident among younger subjects, men, HbsAg-positive individuals, never smokers, never drinkers, and subjects without family history of cancer. These results suggest that the presence of the NQO1 C609T polymorphism may be a marker of genetic susceptibility to HCC.     

Animal products and K-ras codon 12 and 13 mutations in colon carcinomas

K-ras gene mutations (codons 12 and 13) were determined by PCR-based mutant allele-specific amplification (MASA) in tumour tissue of 185 colon cancer patients: 36% harboured mutations, of which 82% were located in codon 12. High intakes of animal protein, calcium and poultry were differently associated with codon 12 and 13 mutations: odds ratios (OR) and 95% confidence intervals (95% CI) for codon 12 versus codon 13 were 9.0 (2.0-42), 4.1 (1.4-12) and 15 (1.4-160), respectively. In case-control comparisons, high intakes of animal protein and calcium were positively associated with colon tumours harbouring codon 12 mutations [for animal protein per 17 g, OR (95% CI) = 1.5 (1.0-2.1); for calcium per 459 mg, 1.2 (0.9-1.6)], while inverse associations were observed for tumours with K-ras mutations in codon 13 [for animal protein 0.4 (0.2-1.0); for calcium 0.6 (0. 3-1.2)]. Transition and transversion mutations were not differently associated with these dietary factors. These data suggest a different dietary aetiology of colon tumours harbouring K-ras codon 12 and 13 mutations.     

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.     

The association of XPC polymorphisms and tea drinking with colorectal cancer risk in a Chinese population

The xeroderma pigmentosum complementation group C (XPC) is responsible for removal of bulky helix-distorting DNA lesions. Several polymorphisms of XPC gene may modulate the colorectal cancer (CRC) susceptibility. We assessed the association of XPC Lys939Gln (A/C), Ala499Val (C/T), and PAT (-/+) polymorphisms with CRC risk in a population-based case-control study which included 421 CRC patients and 845 controls. For Lys939Gln, the CC genotype was associated with a significantly increased risk of CRC (odds ratio (OR)=1.5; 95% confidence interval (CI)=1.0-2.2) compared with the AA genotype. The subjects with PAT +/+ genotype had a significantly increased risk of CRC (OR=1.5; 95% CI=1.0-2.3), compared with those with PAT-/- genotype. Though no significant association between Ala499Val and CRC risk was observed, we found that individuals carrying the CT+TT genotypes showed a significantly decreased risk of rectal cancer (OR=0.7; 95% CI=0.5-1.0). Additionally, the haplotype C+C was associated with a significantly increased CRC risk (OR=1.3; 95% CI=1.0-1.6), compared with the most common haplotype A-T. Further, individuals with four or more risk alleles exhibited a significantly increased risk of CRC (OR=1.4; 95% CI=1.0-2.0), with a significant gene-dosage effect (P for trend=0.038). Besides, never tea drinking was associated with a significantly increased risk of CRC (OR=2.3; 95% CI=1.7-3.3). Our results suggest that the XPC polymorphisms may modulate CRC susceptibility independently or jointly, and tea drinking has a protective effect on CRC.     

DNA repair gene polymorphisms and probability of p53 mutation in bladder cancer

We investigated if the presence of single nucleotide polymorphisms (SNPs) in the XRCC1, XRCC3, and XPD genes were associated with the type and frequency of p53 mutations in bladder cancer. Using a hospital-based case-control study we have previously reported risks for the XRCC1 codon 194, XRCC1 codon 399, XRCC3 codon 241, and XPD codon 751 SNPs 1-3. We have also previously reported mutation data for 149 cases from this study who were screened for mutations in exons 4 through 9 of the p53 gene 4. Here we investigate possible associations between the DNA repair SNPs mentioned above and the presence of p53 mutations by comparing the frequency of each genotype between p53 mutation positive and negative cases. We also considered different classes of p53 mutations, including any mutation (nonsense, missense or silent), transversions and transitions and estimated odds ratios (ORs) and 95% confidence intervals (CI) for these associations. Cases with the XRCC1 codon 399 Gln/Gln genotype were positively associated with the presence of p53 transversions (OR = 4.8; 94% CI = 0.8-30). Cases with the XPD codon 751 Gln/Gln genotype were positively associated with the presence of p53 transitions (OR = 2.8; 95% CI = 0.8-9.3), in particular G:C-A:T transitions (OR = 3.7; 95% CI = 1.1-13). Our data provide some limited support for the hypothesis that mutations in the p53 gene in bladder cancer may differ according to the presence or absence of certain DNA repair gene variants.     

DNA修复基因XPD XPC XRCC4基因多态性与结直肠癌易感性的关联性研究

  目的  探讨DNA修复基因XPD rs13181（codon751A/C,Lys751Gln）、rs238406（codon156C/A,Arg156Arg）、XPC rs2279017（i11C/A）和XRCC4 rs3734091（codon247T/C,Ala247Ser）的单核苷酸多态性与结直肠癌易感性的关系。  方法  采用TaqMan技术对2013年4月至2016年1月北京肿瘤医院收治的338例结直肠癌患者（病例组）和315例健康者（对照组）进行多态位点基因型的检测。  结果  XPD rs13181基因型GT和等位基因G增加个体结直肠癌的发病风险（GT>TT,adjusted OR=1.69,95%CI:1.15~2.47,P=0.007;G>T,adjusted OR=1.77,95%CI:1.19~2.64,P=0.005）;XRCC4 rs3734091基因型GT和等位基因T增加个体结直肠癌的易感性（GT>GG,adjusted OR=9.02,95%CI:5.61~14.50,P＜0.001;T>G,adjusted OR=4.06,95%CI:2.49~6.61,P＜0.001）;XPD rs13181和rs238406的单倍体型GT显著降低结直肠癌的发病风险（adjusted OR=0.39,95%CI:0.18~0.85,P=0.018）。XPCrs2279017等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=28.43,95%CI:6.85~117.95,P＜0.001）以及XPD rs13181等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=10.24,95%CI:4.69~22.35,P＜0.001）显著增加个体结直肠癌的易感性。  结论  XPD rs13181和XRCC4 rs3734091位点的多态性与结直肠癌的易感性相关。