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

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.

Keywords: NQO1; case-control study; prostate cancer; restriction fragment length polymorphism analysis.

Figure 1

(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.

Figure 2

Distribution of the NQO1 C⁶⁰⁹T polymorphism published European male control cohorts.

Figure 3

(a) Distribution of the NQO1 C⁶⁰⁹T polymorphism in our cohorts (p = 0.242); (b) Distribution of the putative risk allele NQO1 ⁶⁰⁹T in our study population (p = 0.146).

Figure 3

(a) Distribution of the NQO1 C⁶⁰⁹T polymorphism in our cohorts (p = 0.242); (b) Distribution of the putative risk allele NQO1 ⁶⁰⁹T in our study population (p = 0.146).

Figure 4

(a) Distribution of the NQO1 C⁶⁰⁹T polymorphism and the putative risk allele NQO1 ⁶⁰⁹T; (b) in healthy controls and PCa patients from all published European studies.

Figure 4

(a) Distribution of the NQO1 C⁶⁰⁹T polymorphism and the putative risk allele NQO1 ⁶⁰⁹T; (b) in healthy controls and PCa patients from all published European studies.