Association of Bladder Cancer Risk with an NAD(P)H:Quinone Oxidoreductase Polymorphism in an Ethnic Kashmiri Population

NQO1 gene polymorphism at nucleotide 609 (Pro187Ser) results in a lowering of NQO1 detoxifying activity and is associated with susceptibility to various cancers. The NQO1 genotypes were identified by RFLP in 104 bladder cancer cases and 120 control subjects in an ethnic Kashmiri population. The frequency of the variant NQO1 alleles (CT/TT) was 23.3% for controls and 32.2% for cases (P?相似文献   

An association between a NQO1 genetic polymorphism and risk of lung cancer

NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that protects against the regeneration of reactive oxygen species chemically induced by oxidative stress, cytotoxicity, mutagenicity, and carcinogenicity. The protection conferred by NQO1 protein reduces certain environmental carcinogens, such as nitroaromatic compounds, heterocyclic amines, and possible cigarette smoke condensate. The gene coding for NQO1 has a genetic polymorphism (C-->T) at nucleotide position 609 (i.e. amino acid codon 187) of the NQO1 cDNA. This polymorphism was shown to reduce NQO1 enzyme activity, thereby diminishing the protection provided by NQO1. Therefore, we hypothesized that individuals with the variant NQO1 genotype are at higher risk for lung cancer. Using a case-control study, we genotyped the NQO1 variants successfully by PCR-RFLP in 826 lung cancer patients and 826 healthy control subjects matched for age, sex, ethnicity, and smoking status. The frequency of the NQO1 T-allele was statistically significantly different among three ethnic groups (p<0.001). In further analysis of Caucasians, the variant NQO1 genotypes (CT and TT) were associated with a marginally increased lung cancer risk (OR=1.19; 95% CI: 0.95-1.50). The elevated lung cancer risk was only evident in younger individuals (age <62 years old) (OR=1.46; 95% CI: 1.04-2.05), women (OR=1.89; 95% CI: 1.33-2.68), and never smokers (OR=1.80; 95% CI: 1.03-3.13). Furthermore, we found a statistically significant trend in the development of lung cancer at an early age in women with increasing copies of the variant allele (p=0.03). These results suggest that the NQO1 variant genotype may modulate lung cancer risk, especially in younger individuals (age<62), women, and never smokers.     

The Association between NQO1 Pro187Ser Polymorphism and Bladder Cancer Susceptibility: A Meta-Analysis of 15 Studies

Background

NAD(P)H:quinone oxidoreductase 1 (NQO1), an obligate two-electron reductase, plays an important role in reducing reactive quinones to less reactive and less toxic hydroquinones. Genetic variations in NQO1 gene that impede its enzyme function may be considered as putative risk factor for cancer. Numerous studies have been performed to investigate the association between NQO1 Pro187Ser polymorphism and bladder cancer risk; nevertheless, the results remain controversial.

Methods

We indentified eligible publications from PubMed, Embase and CBM databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the strength of the associations. False-positive report probability (FPRP) analysis was also performed for all statistically significant findings.

Results

We collected a total of 15 studies including 4298 cases and 4275 controls in the final meta-analysis. Overall, the NQO1 187Ser carriers were associated with an increased bladder cancer risk (homozygous: OR = 1.43, 95% CI = 1.08-1.90; recessive: OR = 1.33, 95% CI = 1.03-1.72; dominant: OR = 1.19, 95% CI = 1.04-1.37, and allele comparing: OR = 1.18, 95% CI = 1.06-1.33). Stratification analyses showed a statistically significant association among Asians (homozygous: OR = 1.82, 95% CI = 1.39-2.38; recessive: OR = 1.52, 95% CI = 1.20-1.93, dominant: OR = 1.40, 95% CI = 1.05-1.88, and allele comparing: OR = 1.35, 95% CI = 1.15-1.58), never smokers (homozygous: OR = 2.30, 95% CI = 1.14-4.65; heterozygous: OR = 2.26, 95% CI = 1.43-3.56; dominant model: OR = 1.59, 95% CI = 1.14-2.21, and allele comparing: OR = 1.72, 95% CI = 1.27-2.33), hospital-based studies (homozygous: OR = 1.46, 95% CI = 1.09-1.94; recessive: OR = 1.32, 95% CI = 1.02-1.69; dominant: OR = 1.28, 95% CI = 1.05-1.56, and allele comparing: OR = 1.24, 95% CI = 1.07-1.43), studies with genotyping performed by PCR-RFLP under all genetic models, and studies with minor allele frequency >0.30 (homozygous: OR = 1.69, 95% CI = 1.25-2.27; recessive: OR = 1.46, 95% CI = 1.10-1.95, and allele comparing: OR = 1.25, 95% CI = 1.04-1.51), respectively.

Conclusions

Despite some limitations, our meta-analysis provides sufficient evidence that NQO1 Pro187Ser polymorphism may contribute to bladder cancer risk. These findings need further validation in well-designed prospective studies with larger sample size and different ethnicities, especially for Asians.     

Susceptibility of XPD and RAD51 genetic variants to carcinoma of urinary bladder in North Indian population

For the present study, two polymorphisms, xeroderma pigmentosum, complementation group D (XPD) Lys751Gln and RAD51 135G/C were studied with regard to bladder cancer. For XPD Lys751Gln polymorphism, an increased risk of bladder cancer was found to be associated with the Gln variant allele (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.27-2.73), on taking AA (Lys/Lys) as the referent genotype. In males, the XPD 751C (Gln) allele was found to be associated with a significantly increased risk (OR=2.33, 95% CI=1.52-3.56). The inhabitants of rural areas showed a significantly increased risk with the XPD Gln allele (OR=2.59, 95% CI=1.46-4.62) when compared with those of urban areas. In smokers (OR=5.30, 95% CI=2.42-11.68), alcohol drinkers (OR=4.33, 95% CI=2.17-8.70), and nonvegetarians (OR=2.21, 95% CI=1.26-3.87), the XPD Gln allele showed a significantly increased risk toward bladder cancer. For RAD51 135G/C polymorphism, no significant difference was observed in the allelic and genotypic frequencies. Even after stratification, no significant association could be seen. After stratifying histopathologically, the RAD51 CC genotype was associted with decreased risk in subjects having superficial stage (OR=0.51, 95% CI=0.27-0.99) and with those having G2 grade (OR=0.24, 95% CI=0.09-0.62) of bladder cancer. XPD polymorphism may be a predisposing factor, but the same cannot be said for RAD51 gene polymorphism.     

Effects of N-acetyl transferase 1 and 2 polymorphisms on bladder cancer risk in Caucasians

Cigarette smoking is the predominant risk factor for bladder cancer (BC). Major carcinogens present in tobacco smoke include a number of aromatic and heterocyclic amines. Two distinct N-acetyl transferase (NAT) enzymes, NAT1 and NAT2, play important roles in the bio-activation and detoxification of these carcinogens. Genes encoding NAT1 and NAT2 are highly polymorphic among human populations, and these polymorphisms result in rapid or slow acetylator phenotypes. Recent studies have suggested that variant alleles leading to slow acetylation by the NAT2 enzyme or rapid acetylation by the NAT1 enzyme constitute possible risk factors for bladder cancer. In this case-control study, we sought to determine whether NAT1 and NAT2 polymorphisms are associated with bladder cancer risk in the largest sample size to date. PCR-RFLP assay was used to determine the presence of NAT1 and NAT2 polymorphisms in 507 Caucasian BC patients and 513 age-, gender-, and ethnicity-matched healthy controls. Overall, we found no significant association between BC risk and NAT1 NAT1*10 allele (OR=0.95; 95% CI 0.73-1.25). However, our data suggested that NAT2 slow acetylator genotypes were associated with a significant increased risk of BC (OR=1.31; 95% CI, 1.01-1.70). This elevated risk appeared more evident in older individuals (OR=1.41; 95% CI, 1.01-1.98) than in younger individuals (OR=1.15; 95% CI, 0.76-1.74). Moreover, the risk was greater for heavy smokers (OR=2.11; 95% CI, 1.33-3.35) than light smokers (OR=0.96; 95% CI, 0.61-1.53) and never smokers (OR=1.23; 95% CI, 0.79-1.90). Finally, a joint effect between NAT2 slow acetylators and heavy smokers was observed. Using never smokers with NAT2 rapid acetylator genotypes as a reference group, heavy smokers with NAT2 slow acetylator genotypes showed an over six-fold increase in BC risk. In a multiplicative interaction model, the interaction term was statistically significant (P=0.02). Our data suggest that having a NAT2 slow acetylator genotype is a significant risk factor for BC, particularly in smokers and older individuals.     

Meta-analysis of the NAD(P)H: quinine oxidoreductase 1 gene 609 C>T polymorphism with esophageal cancer risk

Association between the NAD(P)H: quinine oxidoreductase 1 (NQO1) gene 609 C>T polymorphism and esophageal cancer (EC) has been widely evaluated; however, the results are often irreproducible. We thus aimed to comprehensively evaluate this association through a meta-analysis. Data were extracted from 10 study populations involving 1390 EC patients and 1812 controls, and were analyzed using STATA software. Random-effects model was applied irrespective of between-study heterogeneity, which was assessed by the inconsistency index (I(2)) statistic. Publication bias was weighted by the funnel plot and Egger's test. Genotype distributions of the NQO1 gene 609 C>T polymorphism met Hardy-Weinberg equilibrium in controls for all studies. Allelic comparison indicated that NQO1 609 T allele conferred an increased risk (odds ratio [OR]=1.23; 95% confidence interval [CI]: 1.02-1.49; p=0.035), accompanying significant heterogeneity (I(2)=63.4%, p=0.003) and no publication bias (p(Egger)=0.391). This association was potentially enhanced in homozygous comparison (OR=1.58; 95% CI: 1.03-2.41; p=0.035; I(2)= 55.4%, p(heterogeneity)=0.017 and p(Egger)=0.461). Under dominant and recessive models, similar associations were obtained with an increased, although marginally significant risk. Subgroup analysis by ethnicity supported the risk profiles of the NQO1 gene 609 T allele and 609 TT genotype with EC in Eastern Asians, not in Europeans. Meta-regression analysis indicated that association between the NQO1 gene 609 C>T polymorphism and EC risk was significantly decreased with aging in case-patients (R(2)=-0.57; p=0.042). We expand previous studies by showing that the NQO1 gene 609 C>T polymorphism might contribute to EC occurrence, especially in Eastern Asians.     

Role of NQO1 609C>T and NQO2 ?3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis

Esophageal cancer (EC) is a complex multifactorial disorder, where environmental and genetic factors play major role. NADPH:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are phase II cytosolic enzymes that catalyze metabolism of quinones, important in the detoxification of environmental carcinogens. A case-control study was performed to investigated the associations of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to EC in a high-risk Kashmiri population of India in 135 EC patients and 195 unrelated healthy controls using PCR-RFLP. We also performed a meta analysis of nine published studies (1,224 cases and 1,740 controls) on NQO1 609C>T and evaluated the association between the NQO1 609C>T polymorphisms and esophageal cancer risk. A significant difference in NQO1 609C>T and NQO2 -3423G>A genotype distribution between EC cases and corresponding controls groups was observed (OR = 2.65; 95 % CI = 1.29-5.42 and OR = 1.88; 95 % CI = 1.02-3.49 respectively). Further, gene-gene interaction showed significantly increased risk for esophageal adenocarcinoma with variant genotypes of NQO1 609C>T and NQO2 -3423G>A polymorphisms and interaction with environmental risk factors revealed pronounced risk of EC with NQO1 609C>T TT genotype in high salted tea users of Kashmir valley (OR = 3.72, 95 % CI = 0.98-14.19). Meta analysis of NQO 609C>T polymorphism also suggested association of the polymorphism with EC in Asians as well as Europeans. In conclusion, NQO1 609C>T and NQO2 -3423G>A genetic variations modulate risk of EC in high-risk Kashmir population.     

SULT1A1 Arg213His polymorphism, smoked meat, and breast cancer risk: a case-control study and meta-analysis

SULT1A1 is involved in both detoxification of estrogens and bioactivation of carcinogens in smoked meat. SULT1A1 Arg213His polymorphism's effect on breast cancer risk is still unclear. We recruited 400 case-control pairs to investigate the association between SULT1A1 genotypes and breast cancer risk, and the combined effect of SULT1A1 polymorphism and daily intake of smoked meat. Participants were questioned about their dietary habits and other risk factors, and their SULT1A1 genotypes were determined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by multivariable unconditional logistic regression. We also performed a meta-analysis of relevant published studies to test these associations. In the case-control study, no significant associations were observed between SULT1A1 polymorphism and breast cancer risk. In the meta-analysis, SULT1A1 His/His genotype slightly increased risk among both overall and postmenopausal women (OR(pooled-overall)=1.12, 95% CI: 1.02-1.24; OR(pooled-post)=1.17, 95% CI: 1.03-1.32). A larger positive association was observed in Asian populations (OR(pooled-Asian)=2.01, 95% CI: 1.24-3.26). In our case-control study, high energy-adjusted daily intake of smoked meat was significantly associated with breast cancer risk in overall, pre- and postmenopausal women (aORs: 2.31-3.13, OR 95% CIs exclude 1). High smoked meat intake interacted positively with the His variant allele (all γ>1). These results correlated with those of the meta-analysis (γ(pooled-overall)=1.27). The SULT1A1 His/His genotype may increase the risk of breast cancer among Asian women, and dietary exposure to heterocyclic amines and polycyclic aromatic hydrocarbons, along with the SULT1A1 His/His variant genotype, may synergistically increase the risk of breast cancer.     

DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic

Colorectal cancer represents a complex disease where susceptibility may be influenced by genetic polymorphisms in the DNA repair system. In the present study we investigated the role of nine single nucleotide polymorphisms in eight DNA repair genes on the risk of colorectal cancer in a hospital-based case-control population (532 cases and 532 sex- and age-matched controls). Data analysis showed that the variant allele homozygotes for the Asn148Glu polymorphism in the APE1 gene were at a statistically non-significant increased risk of colorectal cancer. The risk was more pronounced for colon cancer (odds ratio, OR: 1.50; 95% confidence interval, CI: 1.01-2.22; p=0.05). The data stratification showed increased risk of colorectal cancer in the age group 64-86 years in both individuals heterozygous (OR: 1.79; 95% CI: 1.04-3.07; p=0.04) and homozygous (OR: 2.57; 95% CI: 1.30-5.06; p=0.007) for the variant allele of the APE1 Asn148Glu polymorphism. Smokers homozygous for the variant allele of the hOGG1 Ser326Cys polymorphism showed increased risk of colorectal cancer (OR: 4.17; 95% CI: 1.17-15.54; p=0.03). The analysis of binary genotype combinations showed increased colorectal cancer risk in individuals simultaneously homozygous for the variant alleles of APE1 Asn148Glu and hOGG1 Ser326Cys (OR: 6.37; 95% CI: 1.40-29.02; p=0.02). Considering the subtle effect of the DNA repair polymorphisms on the risk of colorectal cancer, exploration of gene-gene and gene-environmental interactions with a large sample size with sufficient statistical power are recommended.     

Association between the p73 exon 2 G4C14-to-A4T14 polymorphism and cancer risk: a meta-analysis

The TP53 homolog p73 is structurally and functionally similar to TP53 and plays an important role in modulating cell-cycle control, apoptosis, and cell growth. G4C14-to-A4T14 is the most commonly studied polymorphism of this gene for its association with risk of cancers, but the results are confusing rather than conclusive. We performed a meta-analysis using 21 eligible studies with a total of 7581 patients and 10,413 controls to summarize the data for an association between the p73 G4C14-to-A4T14 polymorphism and cancer risk. Compared with the common GC/GC genotype, the AT carriers (AT/GC, AT/AT) had a 1.18-fold elevated risk of cancer (95% confidence interval [CI]=1.11-1.25, p<0.00001) in a dominant genetic model as estimated in a fixed effect model. The effect of the G4C14-to-A4T14 polymorphism was further evaluated through stratification analysis. In four lung cancer studies, the variant genotypes had a significantly increased risk of lung cancer (odds ratio [OR]=1.16, 95% CI=1.04-1.28, p=0.005). Similar phenomena were also found in two squamous cell carcinoma of the head and neck studies (OR=1.32, 95% CI=1.12-1.56, p=0.0010), two oral cancer studies (OR=1.57, 95% CI=1.26-1.95, p<0.0001), and three colorectal cancer studies (OR=1.23, 95% CI=1.01-1.50, p=0.04). Increased risk of cancer associated with G4C14-to-A4T14 variant genotypes was pronounced in Caucasians (OR=1.21, 95% CI=1.11-1.31, p<0.00001), the Japanese population (OR=1.24, 95% CI=1.01-1.52, p=0.04), and the Korean population (OR=1.27, 95% CI=1.07-1.52, p=0.007). Our meta-analysis suggests that the p73 G4C14-to-A4T14 polymorphism genotypes (GC/AT+AT/AT) may be associated with an increased risk of cancer in most cancer types and ethnicities.     

P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case–control studies

To explore the real association between p53 codon 72 polymorphism and lung cancer risk, a pooled analysis of 32 case–control studies involving 19,255 subjects was conducted. When all 32 studies were pooled into the analysis, significantly elevated lung cancer risks were associated with variant genotypes in all genetic models (for Pro/Arg vs. Arg/Arg: OR 1.21, 95% CI 1.01–1.23; for Pro/Pro vs. Arg/Arg: OR 1.20, 95% CI 1.03–1.39; for Pro/Pro + Pro/Arg vs. Arg/Arg: OR 1.14, 95% CI 1.03–1.25; for Pro/Pro vs. Arg/Arg + Pro/Arg: OR 1.06, 95% CI 1.01–1.12). In the subgroup analysis by ethnicity, histological type, or smoking status, significantly increased risks were found in subgroups such as Asians, Caucasians, lung adenocarcinoma patients, or smokers, respectively. In conclusion, our results suggest that the Pro allele at p53 codon 72 is emerging as a low-penetrance susceptibility allele for lung cancer development.     

The XRCC1 Arg280His polymorphism contributes to cancer susceptibility: an update by meta-analysis of 53 individual studies

The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in DNA repair pathways. Epidemiological studies have revealed the association between XRCC1 Arg280His polymorphism and cancer risk, but the results were inconsistent. We conducted this meta-analysis to assess the effect of XRCC1 Arg280His polymorphism on cancer susceptibility with accumulated data. Up to January 2012, 53 case‐control studies with 21,349 cases and 23,649 controls were available for our study. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for XRCC1 Arg280His polymorphism and cancer were estimated using fixed‐ or random-effects models when appropriate. Our meta-analysis identified that elevated cancer risk was statistically associated with the minor variant His allele and Arg–His/His–His genotypes both in the overall population (allele comparison, His versus Arg: OR = 1.16; 95% CI: 1.08–1.25; dominant comparison, Arg–His/His–His versus Arg–Arg: OR = 1.17; 95% CI: 1.08–1.27) and in terms of subgroup analyses by ethnicity for both Caucasians and non‐Caucasians. However, no significant result was observed in the stratified analysis by cancer type. Moreover, significantly increased cancer risk was observed in smokers. These findings indicated that XRCC1 Arg280His polymorphism may play a role in cancer development.     

Functional polymorphism in the EpCAM gene is associated with occurrence and advanced disease status of cervical cancer in Chinese population

The epithelial cell adhesion molecule (EpCAM) was originally identified as a tumor associated antigen, attributable to its high expression on rapidly proliferating tumors of epithelial origin. EpCAM plays vital roles in carcinogenesis, tumor progression and metastasis in most tumors. A non-synonymous polymorphism (rs1126497 C/T) was found in exon 3 of EpCAM, which cause a transition from 115 Met to 115 Thr. Another polymorphism (rs1421 A/G) in the 3'UTR causes loss of has-miR-1183 binding. We performed a multiple independent case-control analysis to assess the association between EpCAM genotypes and cervical cancer risk. Genotyping a total of 518 patients with cervical cancer and 723 control subjects in a Chinese population, we observed that the variant EpCAM genotypes (rs1126497 CT, and TT) were associated with substantially increased risk of cervical cancer. Compared with the rs1126497 CC genotype, CT genotype had a significantly increased risk of cervical cancer (Crude OR = 1.70; 95% CI = 1.33-2.20; adjusted OR = 1.72; 95% CI = 1.33-2.22), the TT carriers had a further increased risk of cervical cancer (Crude OR = 1.94; 95% CI = 1.01-3.72; adjusted OR = 1.96; 95%CI = 1.01-3.81), and there was a trend for an allele dose effect on risk of cervical cancer (P < 0.001). Moreover, the allele T increases the risk for invasive disease or metastatic disease, compared with C allele. However, there exists no significant difference in genotype frequencies of rs1421 A/G site between cases and controls (P = 0.798). These findings suggest that rs1126497 C/T polymorphism in EpCAM may be a genetic modifier for developing cervical cancer.     

Meta-analysis demonstrates that the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene 609 C>T polymorphism is associated with increased gastric cancer risk in Asians

The association between the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and gastric cancer has been widely evaluated, yet with conflicting results. Data were available from seven study populations involving 2600 subjects. Overall, comparison of alleles 609T and 609C indicated a significantly 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 increased in the homozygous comparison (609TT versus 609CC), with an OR = 2.04 (95%CI = 1.37-3.05). Stratified analysis by study design demonstrated stronger associations in population-based studies than in hospital-based studies, based on OR. Ethnicity-based analysis demonstrated a significant association in Asians but not in Caucasians. Additionally, in the subgroup analyses by the type of gastric cancer, a significantly increased risk was found with all genetic models in the gastric adenocarcinoma subgroup compared to the others. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.     

Role of epoxide hydrolase, NAD(P)H:quinone oxidoreductase, cytochrome P450 2E1 or alcohol dehydrogenase genotypes in susceptibility to colorectal cancer

Colorectal cancer (CRC) is one of the most common forms of cancer in Western countries. CRC has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. Therefore, we determined whether polymorphisms in the genes coding for microsomal epoxide hydrolase (EPHX1), NAD(P)H:quinone oxidoreductase (NQO1), cytochrome P450 2E1 (CYP2E1) and alcohol dehydrogenase (ADH3) predispose to the development of CRC. DNA samples were obtained from 371 patients with sporadic CRC and 415 healthy controls. Patients and controls were all of Caucasian origin. All genetic polymorphisms were determined by polymerase chain reaction, eventually followed by restriction-fragment-length-polymorphism analyses, except for the EPHX1 codon 113 polymorphism, which was genotyped by an allele-specific discrimination assay. Calculation of crude Odds Ratios (ORs) revealed an increased risk for CRC associated with variant NQO1 (OR 1.5, 95% CI 1.1-2.0) and CYP2E1 intron 6 genotypes (OR 2.2, 95% CI 1.3-3.8). However, after adjustment for age and gender, logistic regression analyses only showed a statistically significant risk for CRC associated with variant NQO1 genotypes (OR 1.6, 95% CI 1.03-2.4). No associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, these data suggest that the presence of variant NQO1 genotypes, with expected reduced enzyme activities might enhance susceptibility to CRC.     

Role of NAD(P)H:quinone oxidoreductase polymorphism at codon 187 in susceptibility to lung,laryngeal and oral/pharyngeal cancers

NAD(P)H:quinone oxidoreductase (NQO1) has been proposed to play a protective role against the toxic effects of benzo[a]pyrene quinones. The C⁶⁰⁹T base change in the NQO1 gene, resulting in a Pro¹⁸⁷Ser amino acid change in the protein, has been associated with deficient enzyme activity. We examined whether this polymorphism modified the risks of smoking-related cancers in a case-control study involving patients with lung cancer (n = 150), laryngeal cancer (n = 129), oral/pharyngeal cancer (n = 121) and control individuals (n = 172), all Caucasian smokers. No statistically significant associations were observed between the NQO1 genotypes and smoking-related cancers, although the Ser/Ser genotype was associated with a tendency towards increased risk for lung cancer (odds ratio [OR] = 2.2, 95% confidence interval [CI] 0.7-6.7) and for oral/pharyngeal cancer (OR = 2.3, 95% CI 0.6-8.2). No significant interaction between the NQO1 genotype and either smoking exposure or GSTM1 genotype was found. Our results are consistent with the hypothesis that lack of NQO1 activity may be involved in some smoking-related cancers. However, they were based on small numbers of individuals with the putative atrisk genotype, and the associations did not reach statistical significance. Moreover, these results contrast with those observed in some other ethnic populations, where a protective effect of the NQO1 Ser allele was found. Further studies are therefore clearly needed for a better understanding of the potential role of NQO1 activity in tobacco-related cancers.     

Role of NAD(P)H:quinone oxidoreductase polymorphism at codon 187 in susceptibility to lung, laryngeal and oral/pharyngeal cancers

NAD(P)H:quinone oxidoreductase (NQO1) has been proposed to play a protective role against the toxic effects of benzo[a]pyrene quinones. The C⁶⁰⁹T base change in the NQO1 gene, resulting in a Pro¹⁸⁷Ser amino acid change in the protein, has been associated with deficient enzyme activity. We examined whether this polymorphism modified the risks of smoking-related cancers in a case-control study involving patients with lung cancer (n = 150), laryngeal cancer (n = 129), oral/pharyngeal cancer (n = 121) and control individuals (n = 172), all Caucasian smokers. No statistically significant associations were observed between the NQO1 genotypes and smoking-related cancers, although the Ser/Ser genotype was associated with a tendency towards increased risk for lung cancer (odds ratio [OR] = 2.2, 95% confidence interval [CI] 0.7-6.7) and for oral/pharyngeal cancer (OR = 2.3, 95% CI 0.6-8.2). No significant interaction between the NQO1 genotype and either smoking exposure or GSTM1 genotype was found. Our results are consistent with the hypothesis that lack of NQO1 activity may be involved in some smoking-related cancers. However, they were based on small numbers of individuals with the putative atrisk genotype, and the associations did not reach statistical significance. Moreover, these results contrast with those observed in some other ethnic populations, where a protective effect of the NQO1 Ser allele was found. Further studies are therefore clearly needed for a better understanding of the potential role of NQO1 activity in tobacco-related cancers.     

The E-cadherin (CDH1) -C160A polymorphism and colorectal cancer susceptibility: a meta-analysis

E-cadherin, encoded by the CDH1 gene, involves in invasion and metastasis of cancer cells. CDH1 -C160A polymorphism was shown to contribute to genetic susceptibility to colorectal cancer (CRC). However, the results from different studies remain controversial. This study was conducted to further explore the association between CDH1 -C160A genetic polymorphism and CRC susceptibility by means of a meta-analysis. A comprehensive literature search was conducted to identify all case-control studies of CDH1 -C160A polymorphism and risk for CRC. A total of nine eligible studies, including 7954 CRC cases and 7369 controls, were identified to the meta-analysis. On the whole, the meta-analysis indicated that CDH1 -C160A genetic polymorphism could reduce the risk of CRC under AA versus CC contrast (odds ratio [OR]=0.86, 95% confidence interval [CI]=0.75-0.98, p(heterogeneity)=0.11), recessive model (OR=0.88, 95% CI=0.77-0.99, p(heterogeneity)=0.23), dominant model (OR=0.92, 95% CI=0.87-0.99, p(heterogeneity)=0.11), and allele A versus allele C contrast (OR=0.93, 95% CI=0.88-0.98, p(heterogeneity)=0.26). A conclusion could be drawn from the research that CDH1 -C160A polymorphism provides a possible protection against CRC, which is especially evident in Caucasian and hospital populations.     

Quantitative assessment of the association between TP53 Arg72Pro polymorphism and bladder cancer risk

Previous studies investigating the association between TP53 Arg72Pro polymorphism and bladder cancer risk reported controversial results. To quantify the strength of association between TP53 Arg72Pro polymorphism and bladder cancer risk, we performed this meta-analysis. We searched PubMed, Embase and Wangfang databases for studies relating the association between TP53 Arg72Pro polymorphism and bladder cancer risk. We used the pooled odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) to assess the association. Finally, data were available from a total of 16 case–control studies including a total of 5, 545 subjects (2,345 cases and 3,200 controls). Meta-analysis of all 16 studies showed TP53 Arg72Pro polymorphism was not associated with bladder cancer risk (All P values were more than 0.10). Subgroup analyses by ethnicity showed that TP53 Arg72Pro polymorphism contributed to bladder cancer risk in East Asians in three genetic models (For Pro vs. Arg, Fixed-effects OR 1.18, 95 % CI 1.05–1.32; For ProPro vs. ArgArg, Fixed-effects OR 1.40, 95 % CI 1.11–1.77; For ProPro vs. ArgPro/ArgArg, Fixed-effects OR 1.32, 95 % CI 1.07–1.62). However, there was no significant association in Caucasians and the others (All P values were more than 0.05). Heterogeneity analyses suggested ethnicity was the major sources of heterogeneity. Thus, meta-analyses of available data suggest the Pro variant of TP53 Arg72Pro contributes to bladder cancer risk in East Asians. Besides, TP53 Arg72Pro polymorphism may have race-specific effects on bladder cancer risk and further studies are needed to elucidate this possible effect.