Association between NQO1 C609T polymorphism and prostate cancer risk

Published studies on the association between NQO1 C609T polymorphism and prostate cancer risk have yielded conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. All eligible studies of NQO1 C609T polymorphism and prostate cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manage 5.0 and Stata 11.0. A total of 6 available studies were considered in the present meta-analysis, with 717 cases and 1,794 controls. When all groups were pooled, there was no evidence that NQO1 C609T had significant association with prostate cancer under additive, recessive, dominant, and allelic models. When stratifying for the race, our analysis suggested that NQO1 C609T was associated with prostate cancer risk in Asians when using dominant (TT + CT vs CC: OR?=?1.419, 95 % CI?=?1.053???1.913, P?=?0.021) and allelic models (OR?=?1.337, 95 % CI?=?1.014???1.763, P?=?0.040) to analyze the data. However, no significant associations were found in Caucasians. This meta-analysis suggested that NQO1 C609T polymorphism most likely contributes to increased susceptibility to prostate cancer in the Asians. Further large-scale and well-designed case–control studies are necessary to validate the risk identified in the present meta-analysis.     

The NQO1 C609T polymorphism and hepatocellular carcinoma risk

NAD(P)H quinine oxidoreductase 1 (NQO1) enzyme plays a crucial role in the protection against oxidative stress. The polymorphism of NQO1 C609T has been implicated in the development of hepatocellular carcinoma (HCC). However, the findings were inconsistent due to different ethnicity, sample size, and source of controls in individual studies. To better estimate the association of NQO1 C609T polymorphism with HCC risk, we performed a meta-analysis of all currently available studies on the susceptibility to HCC. The meta-analysis included three independent studies with a total of 1, 595 subjects. The association was assessed under five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of HCC (OR_{T vs. C}?=?1.47, 95 % CI 1.07–2.00, P _OR?=?0.016; OR_{TT vs. CC}?=?2.06, 95 % CI 1.06–3.98, P _OR?=?0.032; OR_{TC vs. CC}?=?1.33, 95 % CI 1.06–1.67, P _OR?=?0.012; OR_{TT?+?TC vs. CC}?=?1.46, 95 % CI 1.19–1.81, P _OR?TT vs. CC?+?TC?=?1.62, 95 % CI 1.25–2.09, P _OR?NQO1 C609T variant allele and genotypes are more susceptible to HCC, particularly for Asians.     

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

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

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

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

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

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

NQO1基因C6O9T多态性和环境因素与乳腺癌遗传易感性的关系

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

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.     

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 lung cancer risk: a meta-analysis

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

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

Background:

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

Methods:

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

Results:

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

Conclusion:

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

Association between IRS-1 Gly972Arg polymorphism and colorectal cancer risk

In order to make a comprehensive assessment of the potential association between one genetic variant in the insulin receptor substrate 1 (IRS-1) gene, rs1801278, and colorectal cancer (CRC) risk, we conducted a meta-analysis of four epidemiological studies, which included 3,708 CRC cases and 4,176 controls. The data showed that rs1801278 polymorphism was not associated with increased CRC risk in the overall population. When stratifying by the race, the results showed that the rs1801278 polymorphism was associated with increased CRC risk under dominant model in mixed populations. Based on this meta-analysis, we conclude that the IRS-1 rs1801278 polymorphism might be a risk factor for CRC development in mixed populations. Further studies, either with larger sample size or involving other single nucleotide polymorphisms (SNPs) and haplotypes of the IRS-1 gene, are necessary to clarify the contribution of IRS-1 rs1801278 in colorectal carcinogenesis.     

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.     

Association between IL-4 -589C>T polymorphism and colorectal cancer risk

In order to make a comprehensive assessment of the potential association between interleukin-4 (IL-4) -589C>T and colorectal cancer (CRC) susceptibility, we conducted a meta-analysis of six epidemiological studies, which included 1,317 CRC patients and 1,659 controls. The data showed that IL-4 -589C>T was not associated with increased CRC risk in the overall population. In the subgroup analysis of IL-4 -589C>T, the results did not change when the analyses were restricted to race. Based on this meta-analysis, we conclude that IL-4 -589C>T may be not a risk factor for CRC development. Further research is needed to assess possible gene–gene or gene–environment–lifestyle interactions on CRC.     

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     

TGFB1 509 C/T polymorphism and colorectal cancer risk: a meta-analysis

Transforming growth factor β (TGF-β) is a cytokine. The TGF-β signaling pathway plays an important role in controlling cell proliferation and differentiation involved in colorectal carcinogenesis. In mammalian cells, TGFB1 is the most abundant subtype of TGF-β. The 509 C/T polymorphism in TGFB1 has been implicated in colorectal cancer risk. However, published data remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 994 cases and 2,335 controls from five published case–control studies was performed. Overall, significantly increased colorectal cancer risks were found for CC versus TT (OR = 1.62; 95% CI: 1.30–2.02; P _{heterogeneity} = 0.118), TC + CC versus TT (OR = 1.30; 95% CI: 1.08–1.58; P _{heterogeneity} = 0.259) and CC versus TC + TT (OR = 1.48; 95% CI: 1.26–1.75; P _{heterogeneity} = 0.244). In the subgroup analysis by ethnicity, significantly increased risks were also found among Asians for CC versus TT (OR = 1.77; 95% CI: 1.40–2.24; P _{heterogeneity} = 0.519), TC + CC versus TT (OR = 1.38; 95% CI: 1.13–1.68; P _{heterogeneity} = 0.679) and CC versus TC + TT (OR = 1.58; 95% CI: 1.31–1.89; P _{heterogeneity} = 0.340). However, no significant associations were found among Europeans for all genetic models. This meta-analysis showed that TGFB1 509 C allele is a risk factor for developing colorectal cancer in Asians.     

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 MTHFR C677T polymorphism and thyroid cancer risk: a meta-analysis

In the light of the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and thyroid cancer (TC) exist objection, a meta-analysis of the MTHFR C677T polymorphism with thyroid cancer risk was performed. All the available studies were identified through a search of the PubMed, Embase, Web of Science, and Chinese Biomedical Literature Database (CBM) up to March 2014. The association between the MTHFR C677T polymorphism and thyroid cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). A total of five independent studies with 2,554 cases and 2,671 controls were included in our meta-analysis. Significant association was found between MTHFR C677T polymorphism and thyroid cancer risk in recessive model in overall populations (TT vs. TC/CC: OR?=?1.88, 95 % CI?=?1.59–2.21, P?=?0.00), but there was no association between MTHFR C677T polymorphism and thyroid cancer risk found in other four models in overall populations (T vs. C: OR?=?1.25, 95 % CI?=?0.96–1.62, P?=?0.10; TT vs. CC: OR?=?1.11, 95 % CI?=?0.93–1.33, P?=?0.26; TC vs. CC: OR?=?1.23, 95 % CI?=?0.84–1.82, P?=?0.29; TT/TC vs. CC: OR?=?1.28, 95 % CI?=?0.89–1.84, P?=?0.19). In the subgroup analysis base on the ethnicity, the results suggested that MTHFR C677T polymorphism was significantly associated with thyroid cancer risk both in Caucasian and Asian populations in recessive model: (Caucasians: TT vs. TC/CC: OR?=?2.28, 95 % CI?=?1.11–4.67, P?=?0.025; Asians: TT vs. TC/CC: OR?=?1.86, 95 % CI?=?1.57–2.20, P?=?0.00). In conclusions, our meta-analysis suggested that the MTHFR C677T polymorphism is associated with thyroid cancer both in Caucasians and Asians.     

Association between NQO1 Pro187Ser polymorphism and esophageal cancer: a meta-analysis

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an important enzyme which can catalyze the two-electron reduction of quinoid compounds into hydroquinones. NQO1 Pro187Ser polymorphism can change the enzymatic activity of NQO1, and it has been proposed to be associated with risk of esophageal cancer. We performed a meta-analysis to examine the association between NQO1 Pro187Ser polymorphism and esophageal cancer. Odds ratio (OR) with a 95 % confidence interval (95 % CI) was used to assess the association. Twelve case–control studies with 1,725 cases with esophageal cancer and 2,341 controls were finally included in the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer (allele model: OR?=?1.24, 95 % CI 1.06–1.46, P _OR?=?0.009; homozygote model: OR?=?1.59, 1195 % CI 1.10–2.30, P _OR?=?0.013; dominant model: OR?=?1.31, 95 % CI 1.05–1.64, P _OR?=?0.018). In the subgroup analysis by ethnicity, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer in Asians but not in Caucasians. Therefore, the meta-analysis suggests that NQO1 Pro187Ser polymorphism is associated with esophageal cancer risk.     

Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case–control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (OR_{Met allele vs. Thr allele}?=?1.17, 95 % CI 0.97–1.42, P _OR?=?0.102; OR_{MetMet vs. ThrThr}?=?1.32, 95 % CI 0.93–1.87, P _OR?=?0.121; OR_{ThrMet vs. ThrThr}?=?1.17, 95 % CI 0.94–1.45, P _OR?=?0.150; OR_{MetMet + ThrMet vs. ThrThr}?=?1.20, 95 % CI 0.96–1.51, P _OR?=?0.114; OR_{MetMet vs. ThrThr + ThrMet}?=?1.37, 95 % CI 0.98–1.93, P _OR?=?0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case–control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.