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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

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机构： [1]Institute of Pathology, University of Duesseldorf, Moorenstr. 5, D-40225 Duesseldorf, Germany [2]Department of Urology, University of Duesseldorf, Moorenstr. 5, D-40225 Duesseldorf, Germany [3]Institute of Hemostasis and Transfusion Medicine, University of Duesseldorf, Moorenstr. 5, D-40225 Duesseldorf, Germany [4]Laboratory of Molecular Biology, The Fourth Affiliated Hospital, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, China [5]Laboratory of Epidemiology, Hebei Cancer Institute, The Fourth Affiliated Hospital, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, China [6]Department of Thoracic Surgery, The Fourth Affiliated Hospital, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, China [7]School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA

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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 (χ(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.

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大类 | 3 区医学

小类 | 4 区肿瘤学

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Q1 ONCOLOGY

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Q2 ONCOLOGY

影响因子： 3.3 最新[2023版] 3.7 最新五年平均 4.663 出版当年[2003版] 3.7 出版当年五年平均 5.405 出版前一年[2002版] 5.375 出版后一年[2004版]

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第一作者机构： [1]Institute of Pathology, University of Duesseldorf, Moorenstr. 5, D-40225 Duesseldorf, Germany [4]Laboratory of Molecular Biology, The Fourth Affiliated Hospital, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, China

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