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NAD(P)H:quinone oxidoreductase 1 (NQO1) P187S polymorphism and prostate cancer risk in Caucasians.

Stoehr CG, Nolte E, Wach S, Wieland WF, Hofstaedter F, Hartmann A, Stoehr R - Int J Mol Sci (2012)

Bottom Line: NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen.A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity.The SNP has also no influence on histopathological characteristics of the tumors.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Hospital Erlangen, Erlangen 91054, Germany; E-Mails: christine.stoehr@uk-erlangen.de (C.G.S.); arndt.hartmann@uk-erlangen.de (A.H.).

ABSTRACT
NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1(609)TT genotype, and low to intermediate activity was detected in NQO1(609)CT genotype compared with (609)CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy-Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.

No MeSH data available.


Related in: MedlinePlus

(a) Representative example for RFLP analysis. St.: size standard; 1–9: DNA from prostate cancer patients; 10: positive control (DNA from bladder cancer cell line RT4); 11: negative control (H2O); (b) Results from sequencing analysis of samples 4, 5 and 7 from (a). Both methods showed concordant results.
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f1-ijms-13-10959: (a) Representative example for RFLP analysis. St.: size standard; 1–9: DNA from prostate cancer patients; 10: positive control (DNA from bladder cancer cell line RT4); 11: negative control (H2O); (b) Results from sequencing analysis of samples 4, 5 and 7 from (a). Both methods showed concordant results.

Mentions: The verification of RFLP analysis by sequencing showed 100% concordance between both methods. All results derived from RFLP analysis could be confirmed by sequencing. Representative examples of genotyping are shown in Figure 1a; representative sequencing results are shown in Figure 1b.


NAD(P)H:quinone oxidoreductase 1 (NQO1) P187S polymorphism and prostate cancer risk in Caucasians.

Stoehr CG, Nolte E, Wach S, Wieland WF, Hofstaedter F, Hartmann A, Stoehr R - Int J Mol Sci (2012)

(a) Representative example for RFLP analysis. St.: size standard; 1–9: DNA from prostate cancer patients; 10: positive control (DNA from bladder cancer cell line RT4); 11: negative control (H2O); (b) Results from sequencing analysis of samples 4, 5 and 7 from (a). Both methods showed concordant results.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472723&req=5

f1-ijms-13-10959: (a) Representative example for RFLP analysis. St.: size standard; 1–9: DNA from prostate cancer patients; 10: positive control (DNA from bladder cancer cell line RT4); 11: negative control (H2O); (b) Results from sequencing analysis of samples 4, 5 and 7 from (a). Both methods showed concordant results.
Mentions: The verification of RFLP analysis by sequencing showed 100% concordance between both methods. All results derived from RFLP analysis could be confirmed by sequencing. Representative examples of genotyping are shown in Figure 1a; representative sequencing results are shown in Figure 1b.

Bottom Line: NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen.A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity.The SNP has also no influence on histopathological characteristics of the tumors.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University Hospital Erlangen, Erlangen 91054, Germany; E-Mails: christine.stoehr@uk-erlangen.de (C.G.S.); arndt.hartmann@uk-erlangen.de (A.H.).

ABSTRACT
NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1(609)TT genotype, and low to intermediate activity was detected in NQO1(609)CT genotype compared with (609)CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy-Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.

No MeSH data available.


Related in: MedlinePlus