NQO1 C609T polymorphism and lung cancer susceptibility: Evidence from a comprehensive meta-analysis.
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ABSTRACT:
SUBMITTER: Huang J
PROVIDER: S-EPMC5731955 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEvidence 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.MethodsOur 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.ResultsWe 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%).ConclusionOur results indicate that the C609T polymorphism of the NQO1 gene is an important genetic risk factor in cancer.
| S-EPMC3778271 | biostudies-literature
Project description:IntroductionA FEW STUDIES HAVE REPORTED AN ASSOCIATION BETWEEN NADP(H): quinine oxidoreductase 1 (NQO1) C609T polymorphism and susceptibility to colorectal cancer (CRC). However, the results were inconsistent rather than conclusive. We performed a meta-analysis to examine this association in various populations.Material and methodsEligible articles were identified by a search of several databases up until June 30, 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association.ResultsOverall, 14 case-control studies with 4,461 cases and 5,474 controls were included in this meta-analysis. The results indicated that the NQO1 C609T polymorphism was significantly associated with CRC susceptibility (summary ORs (95% CIs): 1.30 (1.07-1.59) for CT vs. CC, 1.64 (1.15-2.33) for TT vs. CC, 1.34 (1.10-1.64) for TT/CT vs. CC, and 1.43 (1.10-1.87) for TT vs. CT/CC). Subgroup analyses indicated that the T allele was significantly associated with CRC susceptibility in both Asians and Caucasians, and was also observed in high quality studies and hospital-based case-control studies. Specifically, we found a positive association between the NQO1 C609T polymorphism and CRC susceptibility in smokers, but not in non-smokers.ConclusionsThe results of this meta-analysis suggest that the NQO1 C609T polymorphism significantly contributes to increased susceptibility to CRC in both Asians and Caucasians.
| S-EPMC4175766 | biostudies-literature
Project description:Background nad(p)hquinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association.MethodsAll studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsTen studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR=1.145, 95% CI=1.008-1.301, P=0.038; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.177, 95% CI=1.041-1.331, P=0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR=1.180, 95% CI=1.035-1.344, P=0.013; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.191, 95% CI=1.050-1.350, P=0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected.ConclusionsOur meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. Further large and well-designed studies are needed to confirm this association.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504.
| S-EPMC4041044 | biostudies-literature
Project description:BackgroundThe association between NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue.Methodology/principal findingsThis case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions) method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR) = 0.99; 95% confidence interval (CI): 0.92-1.06; P = 0.692) and dominant (OR = 0.98; 95% CI: 0.89-1.08; P = 0.637) models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis.ConclusionsOur study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations.
| S-EPMC3480506 | biostudies-literature
Project description:Increasing researches have been performed regarding the relationship between TERT rs2736098 and cancer risk, but no consensus has been reached about the relationship. Here, we conducted this updated meta-analysis, aiming to comprehensively evaluate the role of TERT rs2736098 in cancer risk. We systematically searched potential relevant articles through PubMed, EMBASE, CNKI, and WanFang database before August 2017. A total of 33 studies with 18685 cases and 23820 controls were finally included in the current meta-analysis. We then adopted odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the contributions of TERT rs2736098 to cancer risk. We found that the TERT rs2736098 polymorphism was associated with risk of cancer in overall analysis (AA vs. GG: OR = 1.26, 95% CI = 1.09-1.47; AA vs.OR = 1.22, 95% CI = 1.09-1.36; AA/AG vs. GG: OR = 1.13, 95% CI = 1.02-1.24; A vs. G: OR = 1.11, 95% CI = 1.04-1.20). Furthermore, in analysis stratified by cancer type, ethnicity, control source, quality score, and Hardy-Weinberg equilibrium (HWE) in controls, we found increased risk of cancer among lung cancer, bladder cancer, breast cancer, colorectal cancer, other cancers, Asians, hospital-based subgroup, score > 9 group, as well as controls agreement with HWE group. Despite some limitations, the current meta-analysis represented the largest and the most comprehensive investigations, with the strongest conclusion than ever before. To further explicit the association between TERT rs2736098 and cancer risk, more well-design case-control studies with larger sample size are warranted in the future.
| S-EPMC5707112 | biostudies-literature
Project description:BackgroundNad(p)hquinone 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.MethodsWe 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.ResultsWe 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.ConclusionsDespite 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.
| S-EPMC4300190 | biostudies-literature
Project description:Many studies have examined the association between the CYP1A2 rs2069514 polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. The PubMed was searched for case-control studies published up to Sep 01, 2014. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated. In this meta-analysis, we assessed six published studies involving comprising 1,168 cases and 1,598 controls of the association between CYP1A2 rs2069514 polymorphism and lung cancer risk. For the homozygote A/A and A allele carriers (G/A + A/A), the pooled ORs were 1.47 (95% CI, 1.15-1.99; P=0.007 for heterogeneity) and 1.43 (95% CI, 1.07-1.90; P=0.000 for heterogeneity), when compared with the homozygous wild-type genotype (G/G). In the stratified analysis by ethnicity, the significantly risks were found among non-Asians for both the A allele carriers and homozygote A/A. However, no significant associations were found in Asian population all genetic models. These results from the meta-analysis suggest that CYP1A2 rs2069514 polymorphism contributes to risk of lung cancer among non-Asian population.
| S-EPMC4430729 | biostudies-literature
Project description:Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg's and Egger's tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9-22.9) and 46.1% (95% CI = 40.2-52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09-1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer.
| S-EPMC3840447 | biostudies-literature
Project description:hOGG1 encodes a DNA repair enzyme responsible for the excision of reactive oxygen species (ROS) in damaged DNA. Previous studies have obtained inconsistent results. To validate the association between the hOGG1Ser326Cys polymorphism and lung cancer risk, we performed an updated meta-analysis of 20 studies (8739 cases and 10385 controls) using STATA version 11.1. With this approach, we tested the overall and subgroup association between the SNP and lung cancer susceptibility stratified by ethnicity, control sources, cell histotypes, and smoking status. We demonstrated a novel, significant correlation between the hOGG1 Ser326Cys polymorphism and increased lung cancer susceptibility in Caucasians. Our findings indicate a need for larger-scale studies to verify the association of this SNP with lung cancer risk in Caucasians.
| S-EPMC3409380 | biostudies-other
Project description:Fibroblast growth factor receptor 4 (FGFR4) is a member of receptor tyrosine kinase family. A functional Gly388Arg (rs351855 G>A) polymorphism in FGFR4 gene causes a glycine-to-arginine change at codon 388 within the transmembrane domain of the receptor. Although the FGFR4 rs351855 G>A polymorphism has been implicated in cancer development, its association with cancer risk remains controversial. Here, we have systematically analyzed the association between the rs351855 G>A polymorphism and cancer risk by performing a meta-analysis of 27 studies consisting of 8,682 cases and 9,731 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. The rs351855 G>A polymorphism was associated with an increased cancer risk under the recessive model (OR=1.19, 95% CI=1.01-1.41). Stratified analysis by cancer type indicated the rs351855 G>A polymorphism was associated with an increased risk of breast and prostate cancer, but a decreased risk of lung cancer. This meta-analysis demonstrates the FGFR rs351855 G>A polymorphism is associated with increased cancer risk and suggests it could potentially serve as a chemotherapeutic target or biomarker to screen high-risk individuals.
| S-EPMC5421931 | biostudies-literature