Effect of a 4Month Tea Intervention on Oxidative DNA Damage among Heavy Smokers: Role of Glutathione S-Transferase Genotypes (original) (raw)
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Reduced DNA repair capacity is believed to increase susceptibility to smoking-related cancers. Polymorphisms in several DNA repair genes have been reported but the role of these variants in generating DNA damage phenotypes in human populations has been less well studied. The aim of this study was to determine whether variation in DNA repair genes is related to smokers' increased susceptibility to DNA damage, and the impact of high tea drinking on this. We designed a phase II randomised controlled, 3-arm tea intervention trial to study the effect of high consumption (4 cups per day) of decaffeinated green or black tea or water on oxidative DNA damage, as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period and to evaluate the roles of XRCC1 genotypes as effect modifiers. A total of 120 heavy smokers were included in the analysis. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by XRCC1 status of the individual. In this randomised controlled trial among smokers, daily drinking of 4 cups of decaffeinated green tea was associated with statistically significant decrease in urinary excretion of 8-OHdG. We did find a greater effect of green tea consumption on urinary 8-OHdG levels among Arg399/Arg (p = 0.02) than among Arg399/Gln+Gln/Gln (p = 0.079) smokers. Decaffeinated black tea consumption had no effect on urinary 8-OHdG levels among heavy smokers. Our data show that consumption of 4 cups of tea per day is a feasible and safe approach and was associated with significant decrease in urinary 8-OHdG among green tea consumers after 4 months of use. Our results suggest that carriers of the polymorphic XRCC1 Gln399 allele may not significantly benefit from a green tea, and hence an antioxidant, intervention.
Effect of a 4-Month Tea Intervention on Oxidative DNA Damage among Heavy Smokers
Cancer Epidemiology, Biomarkers & Prevention, 2004
Glutathione S-transferase (GST), a member of the phase II group of xenobiotic metabolizing enzymes, has been intensively studied at the levels of phenotype and genotype. The GST μ 1 (GSTM1) and GST θ 1 (GSTT1) genes have a null-allele variant in which the entire gene is absent. The null genotype for both enzymes has been associated with many different types of tumors. The aim of this study was to determine the possible differences in increased oxidative stress susceptibility to smoking within the GSTM1 and GSTT1 genotypes and the impact of high tea drinking on this. We designed a Phase II randomized, controlled, three-arm tea intervention trial to study the effect of high consumption (4 cups/day) of decaffeinated green or black tea, or water on oxidative DNA damage, as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect modifiers. A total of 133 heavy smokers (100 females and...
The Journal of nutrition, 2008
The levels of tobacco-related DNA adducts in human tissues reflect a dynamic process that is dependent on the intensity and time of exposure to tobacco smoke, the metabolic balance between activation of detoxification mechanisms, and the removal of adducts by DNA repair and/or cell turnover. Urinary 8-hydroxydeoxyguanosine (8-OHdG) is probably 1 of the most abundant DNA lesions formed during oxidative stress and is proposed as a sensitive biomarker of the overall oxidative DNA damage and repair. We performed this study to determine whether there were differences in increased oxidative stress susceptibility to smoking within the combined GSTM1 and hOGG1 genotypes and the impact of green tea drinking on this. We completed a Phase II randomized, controlled, 3-arm tea intervention trial to study the effect of high consumption of decaffeinated green or black tea or water on urinary 8-OHdG among heavy smokers and to evaluate the roles of GSTM1 and hOGG1 genotypes as effect modifiers. Asse...
Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR) = 4.93; 95% confidence interval (95% CI) = 1.27-19.13) than for drinkers (OR = 1.88; 95% CI = 1.01-3.48). Further, among individuals with the OGG1 Cys 326 allele, daily consumption was associated with a 72% reduction (95% CI = 0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser 326 homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage.
International journal of molecular epidemiology and genetics, 2010
Available in vitro and animal studies have shown cancer protective effects of tea polyphenols. Recent study suggests a greater protective effect of green tea intake on breast cancer risk among women possessing the low-activity associated genotype of the catechol-O-methyltransferase (COMT), which may modulate the metabolism and excretion of tea polyphenols through urine. To determine the effect of COMT genotype on urinary excretion of tea polyphenol metabolites of daily green tea drinkers, a cross-sectional analysis was performed within the Shanghai Cohort Study, a population-based, prospective investigation of diet and cancer in 18,244men. In addition to an in-person interview, each participant provided a blood and urine sample at baseline. In the present study, COMT genotype (rs4680) and five urinary metabolites of tea polyphenols were determined in 660 cohort subjects who self-identified as daily drinkers of green tea. All urinary tea polyphenol measurements were expressed in unit...
Journal of Nutrition and Food Sciences, 2017
Background: Oxidative stress has been implicated as an important modulator of human health and can play a role in both disease prevention and disease development. Objectives: The overall goal of this study was to determine the effects of high tea consumption on biological markers of oxidative stress that mediate lung cancer risk, including, 8-hydroxydeoxy-guanosine (8-OHdG) and F2-isoprostanes (8-iso-PGF2α). Design: We completed a 6-month randomized, controlled, double-blinded trial in a group of former and current smokers who were randomized to receive green or black tea preparations or a matching placebo. Results: A total of 146 participants (80 females and 66 males) completed the study. At the end of the 6-month intervention, female smokers in the green tea group showed a 35% decrease (p=0.04) in DNA damage while female former smokers in the black tea group showed a 26% decrease (p=0.015) in lipid damage. No significant changes in markers of oxidative stress were observed in men. Conclusion: This data confirm our previous findings related to the beneficial effect of green tea on oxidative DNA damage among female smokers. The significant beneficial effect of black tea on oxidative lipid damage as well as the gender difference merit further studies.
The Effect of Tea Consumption on Oxidative Stress in Smokers and Nonsmokers
Proceedings of the Society for Experimental Biology and Medicine, 1999
While the anticarcinogenic effects of tea in animal models have been reported by several groups, human epidemiological studies examining tea consumption and cancer prevention have produced equivocal results. The beneficial properties of tea to human health may be related to the antioxidant properties of tea components. However, little evidence has been provided that tea consumption can either increase the antioxidant capacity or decrease oxidative stress in humans. In the present study, the effects of tea treatment (green tea) on biomarkers of oxidative stress were investigated in smokers and nonsmokers in two volunteer study groups (one in China and the other in United States). Green tea consumption in both study groups decreased oxidative DNA damage (8-OHdG in white blood cells and urine), lipid peroxidation (MDA in urine), and free radical generation (2,3-DHBA in urine) in smokers. Nonsmokers (US study group) also exhibited a decrease in overall oxidative stress.
Carcinogenesis, 2006
Modulation of urinary excretion of green tea polyphenols (GTPs) and oxidative DNA damage biomarker, 8-hydroxydeoxyguanosine (8-OHdG), were assessed in urine samples collected from a randomized, doubleblinded and placebo-controlled phase IIa chemoprevention trial with GTP in 124 individuals. These individuals were sero-positive for both HBsAg and aflatoxin-albumin adducts, and took GTP capsules daily at doses of 500 mg, 1000 mg or a placebo for 3 months. Twenty-four hour urine samples were collected before the intervention and at the first and third month of the study. Urinary excretion of 8-OHdG and GTP components was measured by HPLC-CoulArray electrochemical detection. The baseline levels of 8-OHdG and GTP components among the three groups showed homogeneity (P 4 0.70), and a nonsignificant fluctuation was observed in the placebo group over the 3 months (P 4 0.30). In GTP-treated groups, epigallocatechin (EGC) and epicatechin (EC) levels displayed significant and dose-dependent increases in both the 500 mg group and 1000 mg group (P 5 0.05). The 8-OHdG levels did not differ between the three groups at the 1 month collection, with medians of 1.83, 2.08 and 1.86 ng/mg-creatinine for placebo, 500 and 1000 mg group, respectively (P ¼ 0.999). At the end of the 3 months' intervention, 8-OHdG levels decreased significantly in both GTP-treated groups, with medians of 2.02, 1.03 and 1.15 ng/mg-creatinine for placebo, 500 mg and 1000 mg group, respectively (P ¼ 0.007). These results suggest that urinary excretions of EGC and EC can serve as practical biomarkers for green tea consumption in human populations. The results also suggest that chemoprevention with GTP is effective in diminishing oxidative DNA damage.
Journal of Negative Results in BioMedicine, 2013
Background: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m 2 ). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees. Results: For ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume ≥6 cups of green tea per day than those who consume ≤1 cup of green tea per day (adjusted OR = 5.647, 95% confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR. Conclusion: The present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.
Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population
International Journal of Cancer, 2005
The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population-based case-control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in-person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR-RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] 5 0.34-1.01). Dose-response relationship was shown (p-trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI 5 1.02-4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI 5 1.62-12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI 5 0.88-6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested. ' 2005 Wiley-Liss, Inc.