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

Zhu, Chenglin; Huang, Qiang; Liu, Chenhai; Lin, Xiansheng; Xie, Fang; Shao, Feng

doi:10.7314/apjcp.2013.14.4.2349

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…[19] included 21 case-control studies and found that the NQO1 C609T polymorphism might be associated with a significantly increased risk of upper digestive tract cancer, but not risk of CRC. The further subgroup analysis by ethnicity showed significant associations for colorectal cancer in Caucasians, but not in Asians [19]. The null association between the NQO1 C609T polymorphism and CRC risk in Asians may be due to the limited number of studies included ( n = 2 studies).…”

Section: Discussionmentioning

confidence: 99%

“…However, other studies showed that there was no relationship between NQO1 polymorphism and CRC susceptibility [10, 11, 14]. Recently, several meta-analyses [16–19] have evaluated the association between the NQO1 C609T polymorphism and risk of colorectal neoplasm. The most recent analysis by Wang et al .…”

Section: Introductionmentioning

confidence: 99%

“…In another meta-analysis, Zhu et al . [19] found that the NQO1 C609T polymorphism might have a significantly increased risk of upper digest tract cancer, but not risk of CRC. That study included 9 studies on CRC involving 4,461 cases and 4,825 controls.…”

Section: Introductionmentioning

confidence: 99%

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Systematic review/Meta-analysis NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis

Zheng¹,

Wang²,

Chai³

2014

aoms

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systematic review/Meta-analysis NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis

Zheng¹,

Wang²,

Chai³

2014

aoms

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“…NQO1 uses NADH or NADPH as substrates to directly reduce quinones to hydroquinones [7,8]. Functions of NQO1 include xenobiotic detoxification, superoxide scavenging and the maintenance of endogenous antioxidant vitamins [9].…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of high NQO1 expression in breast cancers

Yang

Zhang

et al. 2014

J Exp Clin Cancer Res

150

126

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BackgroundNAD (P) H: quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants, providing cytoprotection in normal tissues. However, high-level expression of NQO1 has been correlated with numerous human malignancies, suggesting a role in carcinogenesis and tumor progression. This study aimed to explore the clinicopathological significance of NQO1 and as a prognostic determinant in breast cancer.MethodsA total of 176 breast cancer patients with strict follow-up, 45 ductal carcinoma in situ (DCIS), 22 hyperplasia and 52 adjacent non-tumor breast tissues were selected for immunohistochemical staining of NQO1 protein. Immunofluorescence staining was also performed to detect the subcellular localization of NQO1 protein in MCF-7 breast cancer cells. Eight fresh breast cancers paired with adjacent non-tumor tissues were quantified using real time RT-PCR (qRT-PCR) and western blot. The correlations between NQO1 overexpression and the clinical features of breast cancer were evaluated using chi-square test and Fisher’s exact tests. The survival rate was calculated using the Kaplan–Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazards models.ResultsNQO1 protein showed a mainly cytoplasmic staining pattern in breast cancer. The strongly positive rate of NQO1 protein was 61.9% (109/176) in breast cancer, and was significantly higher than in DCIS (31.1%, 14/45), hyperplasia tissues (13.6%, 3/22) and adjacent non-tumor tissues (13.5%, 7/52). High-level expression of NQO1 protein was correlated with late clinical stage, poor differentiation, lymph node metastasis, Her2 expression and disease-free and 10-year overall survival rates in breast cancer. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.ConclusionsHigh-level expression of NQO1 appears to be associated with breast cancer progression, and may be a potential biomarker for poor prognostic evaluation of breast cancers.

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“…Therefore, there is an urgent need for a better understanding of SCLC pathogenesis that may lead to more effective treatment strategies. NAD(P)H:quinone oxidoreductase-1 (NQO1), which was discovered by Professor Ernster in 1958 (4) and originally called DT-diaphorase (5), is located on chromosome 16q22 (6). Several functions of NQO1 have been proposed, including xenobiotic detoxification, superoxide scavenging, maintenance of endogenous antioxidants, modulation of p53 and proteasomal degradation (7).…”

Section: Introductionmentioning

confidence: 99%

NAD(P)H:quinone oxidoreductase-1 overexpression predicts poor prognosis in small cell lung cancer

et al. 2014

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quinone oxidoreductase-1 (NQO1) is commonly elevated in various types of human cancers, including pancreatic, breast and thyroid cancer, as well as others. However, little is known concerning the status of NQO1 in small cell lung cancer (SCLC). To investigate the clinicopathological significance of NQO1 expression and evaluate its role as a potential prognostic marker in SCLC, protein and mRNA expression levels of NQO1 were determined in four fresh tissue samples of SCLC and paired adjacent non-cancerous tissues using western blotting and real-time qRT-PCR, respectively, and 115 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of NQO1 protein. The correlation between NQO1 expression and the clinicopathological features of SCLC was evaluated using the Chi-square (χ2) and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In regards to the results, levels of NQO1 protein and mRNA were significantly elevated in the four fresh tissue samples of SCLC compared with levels in the paired adjacent non-cancerous tissues, respectively. IHC analysis showed that the rate of strong positive NQO1 protein expression was significantly higher (48.70%) in SCLC when compared with the rate in either adjacent non-cancerous or normal lung tissues (both P<0.001). The rate of strong positive NQO1 protein expression was correlated with large tumor size (P=0.019), late pathologic stage (P=0.001) and the presence of lymph node metastasis (P=0.001). Moreover, high‑level expression of NQO1 protein was significantly correlated with lower disease-free survival (P=0.001) and 5-year survival rates (P<0.001) in SCLC patients, particularly early‑stage patients (P=0.045 and P=0.033, respectively). Further Cox analysis revealed that NQO1 expression emerged as a significantly independent hazard factor for the 5-year survival rate of patients with SCLC (P=0.042). In conclusion, NQO1 plays an important role in the progression of SCLC, and it may potentially be used as a biomarker and therapeutic target of SCLC.

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

Cited by 14 publications

References 32 publications

Systematic review/Meta-analysis NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis

Systematic review/Meta-analysis NQO1 C609T polymorphism and colorectal cancer susceptibility: a meta-analysis

Clinical implications of high NQO1 expression in breast cancers

NAD(P)H:quinone oxidoreductase-1 overexpression predicts poor prognosis in small cell lung cancer

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