The Influence of Fruit and Vegetable Consumption and Genetic Variation on NAD(P)H:Quinone Oxidoreductase (NQO1) Phenotype in an Endoscopy-Based Population

Abstract

NAD(P)H:quinone oxidoreductase (NQO1) is an inducible detoxification enzyme relevant for colorectal cancer biochemoprevention. We evaluated the influence of recent fruit and vegetable (F&V) consumption and polymorphisms in NQO1 and transcription factor NFE2L2 on rectal NQO1 phenotype and also whether white blood cell (WBC) NQO1 activity reflects rectal activity. Among 94 sigmoidoscopy patients, we assessed F&V consumption by dietary record and determined the NQO1 c.609C > T and g.-718A > G and NFE2L2 g.-650C > A, g.-684G > A, and g.-686A > G polymorphisms. NQO1 mRNA level was measured in rectal biopsies and NQO1 activity in rectal biopsies and WBC. Consumption of F&V did not yield higher mRNA level or activity but rather appeared to have a repressive effect. Rectal activity was higher among NQO1 609CC-genotypes as compared to 609CT-genotypes (P < 0.0001; 609TT-genotypes were absent), whereas mRNA was higher among 609CT-genotypes (P < 0.001). mRNA and activity correlated among NQO1 609CC-genotypes (r = .50, P = 0.0001) but not among 609CT-genotypes (r = .14, P = 0.45). The NFE2L2-684A-allele was associated with higher mRNA levels (P = < 0.05). The other polymorphisms did not affect phenotype significantly. WBC and rectal activity did not correlate. In conclusion, genetic variation, especially the NQO1 609C > T polymorphism, is a more important predictor of rectal NQO1 phenotype than F&V consumption. WBC NQO1 activity is not a good surrogate for rectal activity.

ACKNOWLEDGMENTS

We thank Petra Vissink and Els Siebelink for the dietary assessment; Elgin Lichtenauer for development of the NQO1 609 C > T genotyping assay; Lucy Okma, Annie van Schaik, and René te Morsche for lab-related support; the endoscopy staff of the Radboud University Nijmegen Medical Center and the Canisius-Wilhelmina Hospital Nijmegen for their support in recruitment; and all study subjects for their kind participation. This work was supported by the Netherlands Organisation for Health Research and Development (ZonMW), grant number: 21000054, and the Dutch Digestive Diseases Foundation (MLDS), grant number WS 00-31.

Notes

^{a a} e.g., 9.4 means a NQO1:β -actin mRNA ratio of 0.0094.

^{a b} Mean ± sd: 10.2 ± 5.3 and 97 ± 47 for mRNA and activity, respectively.

^{a c} Median split; age: mean ± sd = 46.5 ± 13.8; BMI: mean ± sd = 25.5 ± 4.6.

^{a d} Source: medical record and self-reported.

^{a e} The three most common indications are shown; more than one possibility per individual.

^{a f} Bowel preparation, day before: 17:00 hrs: 2 laxatives (10 mg), 20:00 hrs microlax enema (5 ml).

* p < 0.10 (the difference between the characteric-groups was tested by Wilcoxon test).

^a Average intake on the 2 days preceding endoscopy, 2 food records missing.

^b e.g., 10.3 means a NQO1:β -actin mRNA ratio of 0.0103.

^{a c} Results are similar for combined group of citrus fruit and juice; juice consumption among 21 consumers: 176 ± 117 g.

^{a d} Does not include potato.

** p < 0.05,

*p < 0.10 (the difference between the yes vs. no consumption groups was tested by Wilcoxon and Savage test).

^{a a} e.g., 10.2 means a NQO1:β -actin mRNA ratio of 0.0102.

* p < 0.05,

** p < 0.001,

***p < 0.0001 (the difference between genotypes was tested by Wilcoxon test for two groups and Kruskal Wallis test for three groups; cells with 1 observation were not included in the test).

^a e.g., 8.8 means 9 NQO1: β-actin mRNA ratio of 0.0088.

* p < 0.10, (the difference between NFE2L2 genotypes was tested by Wilcoxon test for two groups and Kruskal Wallis test for three groups; cells with 1 observation were not included in the test).

^a Median value on which low and high fruit and vegetable consumption groups are based: 199.5 g; does not include juice.

^b e.g., 11.0 means a NQO1:β -actin mRNA ratio of 0.011.