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M.J. Tijhuis,
A.M.J.F. Boerboom, M.H.P.W. Visker,
Camp,
E.B.G,
op den,
F M Nagengast,
A.C.I.T.L. Tan,
I.M.C.M. Rietjens,
F.J. Kok,
J.M.M.J.G. Aarts,
E. Kampman
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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.
Nutrition and Cancer 60 (2008) 2.
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ABSTRACT: Thymidylate synthase and serine hydroxymethyltransferase are involved in folate metabolism. In a case-control study, including 768 cases and 709 controls, we investigated the associations between colorectal adenomas and TS tandem repeat and SHMT1 C1420T polymorphisms, and the interplay with B-vitamins. The polymorphisms were not associated with adenomas, but there was a borderline significant interaction between TS genotype and vitamin B6: the association between vitamin B6 and adenomas seemed positive in TS 3R/3R individuals, but inverse in TS 2R/2R individuals. This study does not provide evidence for a role of SHMT1 genotype in adenoma occurrence. Future research has to indicate whether the TS-B6 interplay is a real effect or a chance finding.
Cancer Letters 250 (2007) 1.
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M.J. Tijhuis, M.H.P.W. Visker,
J.M.M.J.G. Aarts,
W H M Peters,
H M J Roelofs,
Camp,
E.B.G,
op den,
I.M.C.M. Rietjens,
A.M.J.F. Boerboom,
F M Nagengast,
F.J. Kok,
E. Kampman
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ABSTRACT: High glutathione S-transferase (GST) activity may contribute to colorectal cancer prevention. Functional polymorphisms are known in the GSTM1, GSTT1, GSTA1 and GSTP1 genes. The influence of these GST polymorphisms and recent fruit and vegetable consumption on GST levels and activity has not been investigated simultaneously in a human population. Also, it is not clear if blood GST activity reflects rectal GST activity. Therefore, we determined GST polymorphisms in 94 patients scheduled for sigmoidoscopy. Rectal GST isoenzyme levels (GSTM1, GSTM2, GSTT1, GSTA and GSTP1) were measured by quantitative Western blotting, and rectal and white blood cell total GST activities were measured spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. Vegetable and fruit consumption was assessed by dietary record. As expected, the GSTM1 and GSTT1 deletion polymorphisms, and the GSTA1 g.-69C>T polymorphism significantly affected the respective isoenzyme levels. Also, rectal GST isoenzyme levels differed between those with and without recent consumption of Alliaceae, Cucurbitaceae, Apiaceae and citrus fruit. Rectal GST activity, however, was not clearly influenced by fruit and vegetable consumption. It was most significantly determined by the GSTP1 c.313A>G polymorphism; compared to the 313AA genotypes, the 313AG and 313GG genotypes showed 36 and 67 nmol/min.mg protein (p<0.001) lower GST activity, respectively. The correlation between rectal and white blood cell GST activities was low (r=0.40, p<0.001), and the relevance of the various genetic and dietary factors appeared to differ between the two tissues. In conclusion, this study indicates that the GST enzyme system is influenced by both GST polymorphisms and consumption of fruits and vegetables. The latter appeared more important for individual rectal GST isoenzyme levels than for total GST activity, which could affect detoxification of isoenzyme-specific substrates. The study results do no support the use of white blood cell GST activity as a surrogate measure for rectal GST activity.
Carcinogenesis 28 (2007) 4.
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ABSTRACT: The possible interplay between cruciferous vegetable consumption, functional genetic variations in glutathione S-transferases (GST) M1, T1, P1, and A1, and colorectal adenomas, was investigated in a Dutch case-control study. The GSTM1 and GSTT1 deletion polymorphisms, and the single nucleotide polymorphisms in GSTP1 (A313G) and in GSTA1 (C-69T) were assessed among 746 cases who developed colorectal adenomas and 698 endoscopy-based controls without any type of colorectal polyps. High and low cruciferous vegetable consumption was defined based on a median split in the control group. High consumption was slightly positively associated with colorectal adenomas [odds ratio (OR) 1.15; 95% confidence interval, 0.92-1.44]. For GSTP1, a positive association with higher cruciferous vegetable intake was only apparent in individuals with the low-activity GSTP1 genotype (GG genotype, OR 1.94; 95% confidence interval, 1.02-3.69). This interaction was more pronounced in men, with higher age and with higher meat intake. The GSTA1 polymorphism may have a modifying role as well: the OR for higher intake compared with lower intake was 1.57 (0.93-2.65) for individuals homozygous for the low expression variant (TT genotype). This seemed to be stronger with younger age and higher red meat intake. Cruciferous vegetable consumption and the combined GSTA1 and GSTP1 genotypes showed a statistically significant interaction (P = 0.034). The GSTM1 and GSTT1 genotypes did not seem to modify the association between cruciferous vegetable intake and colorectal adenomas. In conclusion, GSTP1 and GSTA1 genotypes might modulate the association between cruciferous vegetable intake and colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2943¿51)
Cancer Epidemiology Biomarkers and Prevention 14 (2005) 12.
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ABSTRACT: Both environment and genetics contribute to the pathogenesis and prevention of colorectal neoplasia. NAD(P)H:quinone oxidoreductase (NQO1) is a detoxification enzyme that is polymorphic and inducible. We investigated interactions between lifestyle factors and polymorphisms in NQO1 and its key regulatory transcription factor NFE2L2 in colorectal adenoma risk. The NQO1 c.609C>T and g.-718A>G and NFE2L2 g.-650C>A, g.-684G>A and g.-686A>G polymorphisms were determined among 740 Dutch adenoma cases and 698 endoscopy-based controls. Dietary intake was assessed by food frequency questionnaire, other lifestyle information by questionnaire. The NQO1 609CT genotype was associated with a higher adenoma risk (OR 1.27, 95% CI 1.00-1.62) compared with the 609CC genotype, whereas the 609TT genotype was not (OR 1.03, 95% CI 0.56-1.88). The higher risk with the NQO1 609CT-genotype was seen among smokers (OR 1.96, 95% CI 1.40-2.76), but not among nonsmokers (OR 0.91, 95% CI 0.62-1.35; interaction p = 0.030). Fruit and vegetable consumption did not protect smokers from adenomas and did not interact with the NQO1 609C>T polymorphism or the NFE2L2 polymorphisms. A higher adenoma risk seen with high fruit and vegetable consumption among NQO1 -718GG genotypes was absent among -718GA genotypes (interaction p = 0.071). Gene-gene interactions were observed between the NQO1 609C>T and NFE2L2 -686A>G polymorphisms (interaction p = 0.056) and between the NQO1 -718 G>A and NFE2L2 -650C>A polymorphisms (interaction p = 0.013). In conclusion: the NQO1 609CT genotype is associated with increased adenoma risk among smokers, which is not diminished by high fruit and vegetable consumption. The observed gene-gene interactions may point to a role for NFE2L2 polymorphisms in NQO1-related adenoma formation
International Journal of Cancer 122 (2008) 8.
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ABSTRACT: Background A growing body of research has shown that disparities in resources, including food stores, exist at the neighbourhood level and the greatest disparities are seen in minority neighbourhoods, the same neighbourhoods at increased risk of obesity and diabetes. Less is known about whether differences in availability of resources by African American or Latino race/ethnicity exist within a single minority community. Objective The present study examined whether census blocks either 75% African American (AA) or 75% Latino (L) are associated with food store availability, as compared with racially mixed (RM) census blocks, in East Harlem, New York. Design/methods A cross-sectional study utilising a walking survey of East Harlem was performed. Food stores were classified into: supermarkets, grocery stores, convenience stores, specialty stores, full-service restaurants and fast-food stores. Results One hundred and sixty-five East Harlem census blocks were examined; 17 were AA, 34 were L and 114 were RM. Of AA census blocks, 100% had neither supermarkets nor grocery stores. AA census blocks were less likely to have convenience stores (prevalence ratio (PR) = 0.25, 95% confidence interval (CI) 0.07¿0.86) compared with RM census blocks. In contrast, predominantly L census blocks were more likely to have convenience stores (PR = 1.8, 95% CI 1.20¿2.70), specialty food stores (PR = 3.74, 95% CI 2.06¿7.15), full-service restaurants (PR = 1.87, 95% CI 1.04¿3.38) and fast-food restaurants (PR = 2.14, 95% CI 1.33¿3.44) compared with RM census blocks. Conclusions We found that inequities in food store availability exist by race/ethnicity in East Harlem, New York. This has implications for racial/ethnic differences in dietary quality, obesity and obesity-related disorders.
Public Health Nutrition 11 (2008).
