Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk

BACKGROUND: Cruciferous vegetables are the primary source of isothiocyanates and other glucosinolate derivatives that are known to induce phase II detoxifying enzymes, including glutathione S-transferases (GSTs). OBJECTIVE: We investigated the independent and combined effects of cruciferous vegetable intake and the GSTP1 Ile(105)Val genetic polymorphism on breast cancer risk. DESIGN: Analyses included 3035 cases and 3037 population controls who were participating in the Shanghai Breast Cancer Study and for whom diet and genetic data were complete (87% of cases and 85% of controls). RESULTS: With the use of multivariate logistic regression, the GSTP1 Val/Val genotype was significantly associated with greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous vegetable intake was not significantly associated with breast cancer risk, although subjects reporting greater turnip (P for trend < 0.001) and Chinese cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous vegetable intake and the Val/Val genotype was seen predominantly among premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). CONCLUSIONS: Cruciferous vegetable intake consistent with high isothiocyanate exposure may reduce breast cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the GSTP1 genotype.     

Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk

Cruciferous vegetables contain anticarcinogenic isothiocyanates (ITCs), particularly the potent sulforaphane, which may decrease risk of prostate cancer through induction of phase II enzymes, including glutathione S-transferases (GSTs). We evaluated this hypothesis in a population-based, case-control study of prostate cancer, including 428 men with incident prostate cancer and 537 community controls. An in-person interview included an extensive food-frequency questionnaire. Genotyping for deletions in GSTM1 and GSTT1 was performed in a subset of men who provided blood. Intakes of cruciferous vegetables and of broccoli, the greatest source of sulforaphane, were associated with decreased prostate cancer risk at all levels above the lowest consumers [adjusted 4th quartile odds ratio (OR)=0.58; 95% confidence interval (CI)=0.38, 0.89, and 0.72 (95% CI=0.49, 1.06)], respectively. In relation to genotypes, there was a nonsignificant increase in risk with the GSTT1 null genotype (OR=1.51; 95% CI=0.98, 2.31) but no effects of GSTM1 genotype. However, men with GSTM1-present genotype and high broccoli intake had the greatest reduction in risk (OR=0.49; 95% CI=0.27, 0.89). Our findings provide evidence that two or more servings per month of cruciferous vegetables may reduce risk of prostate cancer, especially among men with GSTM1-present alleles, and are consistent with a role of dietary ITCs as chemopreventive agents against prostate cancer.     

Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype

The role of vegetable consumption in relation to breast cancer risk is controversial. Anticarcinogenic compounds may be present only in specific vegetables, thereby attenuating findings for total vegetable intake. Cruciferous vegetables contain precursors of isothiocyanates (ITCs), which may be chemopreventive through potent inhibition of phase I, and induction of phase II enzymes, such as glutathione S-transferases (GSTs). We investigated associations between consumption of cruciferous vegetables, sources of ITCs, and breast cancer risk, and potential modification of relations by GSTM1 and GSTT1 genotypes. Cases (n = 740) were Caucasian women with incident breast cancer identified from all major hospitals in Erie and Niagara counties. Community controls (n = 810) were frequency matched to cases by age and county. An in-depth interview including a validated FFQ was administered in person. Odds ratios (ORs) and 95% CIs were used to estimate relative risks. Consumption of cruciferous vegetables, particularly broccoli, was marginally inversely associated with breast cancer risk in premenopausal women [4th quartile OR = 0.6, 95% CI (0.40-1.01), P = 0.058]. Associations were weaker or null among postmenopausal women. No significant effects of GST genotype on risk were observed in either menopausal group. These data indicate that cruciferous vegetables may play an important role in decreasing the risk of premenopausal breast cancer.     

Interaction between dietary intake and GSTM1 and GSTT1 polymorphisms in head and neck cancer risk: a case-control study in São Paulo, Brazil

A hospital-based case-control study was conducted to investigate the potential interaction between dietary factors and polymorphisms in phase II metabolic enzymes GSTM1 and GSTT1, associated with head and neck cancer risk. The study included 103 histologically confirmed incident cases and 101 controls. Food intake was estimated with a validated food frequency questionnaire. The gene polymorphisms were evaluated by PCR. Increased risk was observed in the highest tertile of beef consumption in the presence of the GSTM1 (OR = 10.79; 95%CI: 2.17-53.64) and GSTT1 null alleles (OR = 3.41; 95%CI: 0.43-27.21). Assessment of dietary intake considering the ratio between animal product and vegetable consumption showed OR = 2.35 (95%CI: 0.27-19.85) in the intermediate tertile and OR = 3.36 (95%CI: 0.41-27.03) in the highest tertile. The results suggest a possible interaction between meat intake and GSTM1/GSTT1 polymorphisms in modulating the risk of head and neck cancer, influenced by vegetable consumption.     

Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent-induced encephalopathy

In the present study, we investigate whether genetic polymorphism in enzymes involved in the metabolism of organic solvents influences susceptibility to chronic solvent encephalopathy (CSE), which is one of the major effects of long-term exposure to organic solvents. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1 enzymes were determined in a group of male CSE patients (N=97) and controls (N=214). The selection of the patients was based on a standard diagnostic protocol, including interviews, neuropsychological tests and questionnaires directed to somatic, cognitive and mood symptoms and exposure, in combination with well-defined decision rules. As controls, healthy workers of similar socio-economic background, without memory problems and with no known exposure to organic solvents, were included in the study. Comparing patients and controls, higher frequencies of the variant *5B allele of the CYP2E1 gene (OR: 5.8; 95% CI: 1.8-18.8) and of the variant GSTP1*C allele (OR: 0.40; 95% CI: 0.17-0.94) were found. Homozygous carriers of the exon 4 EPHX1 Arg139 variant allele had a lower risk (OR: 0.25; 95% CI: 0.06-1.13). The present study indicates that genetic polymorphism of CYP2E1, EPHX1 and GSTP1 modify the risk of developing CSE.     

Association of Xenobiotic Metabolizing Enzymes Genetic Polymorphisms With Esophageal Cancer in Kashmir Valley and Influence of Environmental Factors

The Kashmir Valley has an elevated incidence rate of esophageal cancer (EC). Several environmental and genetic factors have been suspected for development of EC. A case-control study was performed in 135 EC patients and 195 healthy controls to analyze association of polymorphisms in glutathione S-transferase (GST) mu (GSTM1), GST theta (GSTT1), GST pi (GSTP1), GSTM3, Cytochrome P450 (CYP)1A1, and CYP2E1 genes with susceptibility to EC as well as their interaction with environmental factors such as smoking and high consumption of salted tea in Kashmir valley. All subjects were genotyped through polymerase chain reaction restriction fragment length polymorphism. Data was statistically analyzed using the chi-square test and logistic regression model. Results showed that GSTP1313 val/val and CYP2E1c1c2 genotypes imparted risk for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma [EADC; odds ratio (OR) = 3.24, 95% confidence interval (CI) = 1.30–8.05; OR = 4.20, 95% CI = 1.65–10.70], respectively. GSTM3AB genotype/B allele was found to be associated with low risk for EC. Tobacco smoking through hukka (water pipe) and consumption of salted tea itself were high risk factors for developing EC (OR = 21.44, 95% CI = 11.63–39.54; OR = 14.86, 95% CI = 8.41–26.24), and the risks were modulated through the interaction of GSTM3AB, GSTP1val/val genotypes. In conclusion, GSTP1val/val and CYP2E1c1c2 genotypes/c2 allele increased the risk of ESCC and EADC, respectively, in the Kashmiri population; whereas GSTM3AB genotype imparted lower risk for both ESCC and EADC.     

Usual Cruciferous Vegetable Consumption and Ovarian Cancer: A Case-Control Study

Ovarian cancer is the fifth leading cause of cancer-related deaths among women, primarily due to diagnosis at late stages. Therefore, identification of modifiable risk factors for this disease is warranted. Using the Patient Epidemiology Data System (PEDS), collected from 1981 to 1998 at Roswell Park Cancer Institute, Buffalo, NY, we conducted a hospital-based, case-control analysis of self-reported cruciferous vegetable intake and ovarian cancer among 675 women with primary, incident ovarian cancer, and 1275 without cancer. Cruciferous vegetable intake was queried using a 44-item food frequency questionnaire (FFQ). Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression, adjusting for age, body mass index (BMI), education, smoking status, parity, family history of ovarian cancer, total fruit consumption, total meat consumption, and total noncruciferous vegetable consumption. We observed a significant inverse association for women with highest vs. lowest intakes of total vegetables (OR = 0.65, 95% CI = 0.46–0.92), cooked cauliflower (OR = 0.82, 95% CI = 0.67–0.99), and cooked greens (OR = 0.63, 95% CI = 0.46–0.86) and an inverse, dose-dependent association between cooked cruciferous vegetables intake and ovarian cancer (for each additional ten servings per month, OR = 0.85, 95% CI = 0.76–0.96). These findings suggest that a diet that includes cruciferous vegetables could be an important modifiable risk factor for ovarian cancer.     

Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis

The authors performed a systematic review and meta-analysis to determine the effect of polymorphisms in genes encoding glutathione S-transferases (GSTs), phase II isoenzymes involved in cellular detoxification, on risk of hepatocellular carcinoma (HCC). Fifteen eligible studies were identified: 14 evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3, GSTA1, GSTA4, GSTO1, and GSTO2, respectively. All were case-control studies performed in populations with high (Asian, African) and medium (European) HCC incidence rates. Random-effects meta-analyses suggested a small excess risk of HCC with GSTT1 null (odds ratio (OR) = 1.19, 95% confidence interval (CI): 0.99, 1.44) and possibly GSTM1 null (OR = 1.16, 95% CI: 0.89, 1.53) genotypes. Cumulative meta-analyses demonstrated that both pooled estimators generally trended toward a small excess risk with publication of more recent studies. Results for GSTP1 A313G suggested no excess risk (OR = 0.75, 95% CI: 0.50, 1.15). A number of potentially interesting gene-gene and gene-environment interactions were reported, but these were too few and inconsistent to allow meta-analysis. The overall results suggest that there may be a small excess risk of HCC in individuals with GSTT1 null and possibly also with GSTM1 null genotypes. However, given the relatively limited total number of subjects examined and observed between-study heterogeneity, chance could not be excluded.     

焦炉作业工人外周血淋巴细胞染色体损伤的遗传易感性研究

目的研究外源性化学物代谢酶基因多态性与焦炉作业工人外周血淋巴细胞染色体损伤的关系。方法选取149名焦炉作业工人和24名非职业多环芳烃(PAH)暴露人员作为研究对象,测定其尿中1-羟基芘浓度来反映PAH暴露的内剂量;对照组的外周血淋巴细胞微核水平的上4分位数(6‰)作为判断个体染色体损伤阳性的界值;分析CYP1A1、GSTM1、GSTT1、GSTP1、CYP2E1、NQO1、NAT2和mEH基因的多态性;使用多元logistic回归方程校正职业暴露情况、年龄、性别、吸烟和饮酒状况因素,计算不同基因型工人发生染色体损伤阳性的OR值,并探讨基因间的交互作用。结果调整了173名研究对象的职业暴露、年龄、性别、吸烟和饮酒状况后,GSTM1缺失基因型个体染色体损伤危险度显著性增加(调整OR=2．01,95％CI=1．03—3.91);与NQO1基因P187S位点野生型纯合子个体比较,变异型纯合子个体染色体损伤危险度显著性增加(调整OR=3．18,95％CI=1．18—8．62);与mEH基因H113Y位点野生型纯合子个体比较,变异型纯合子个体染色体损伤危险度显著性降低(调整OR=0．40,95％CI=0.19～0．88);未发现其他基因的遗传变异与研究对象外周血淋巴细胞染色体损伤危险度的显著关联。此外,还发现GSTM1、NQO1基因P187S位点和mEH基因H113Y位点的遗传变异对染色体损伤危险度的影响中存在基因-基因交互作用。结论本研究发现GSTM1、NQO1和mEH基因的遗传变异可显著性影响职业PAH暴露个体外周血淋巴细胞染色体损伤危险度,并存在基因一基因交互作用。     

Genetic Variation in GSTM1 Is Associated With Susceptibility to Noise-Induced Hearing Loss in a Chinese Population

OBJECTIVES:: To investigate whether glutathione S-transferases (GST) genetic polymorphisms (GSTT1 rs1049055, GSTM1 rs10712361, and GSTP1 rs1695) are associated with susceptibility to noise-induced hearing loss (NIHL). METHODS:: These polymorphisms were analyzed in 444 NIHL and 445 normal hearing workers. In addition, total plasma GST activity was measured in all subjects. RESULTS:: Individuals with the GSTM1 null genotype had a statistically significantly increased risk of NIHL (odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.26 to 2.13) compared with those carrying a wild-type GSTM1 genotype. This effect was more pronounced among the workers exposed to 86 to 91 dB(A) (OR = 3.35, 95% CI = 1.54 to 7.31). Glutathione S-transferase activity of the NIHL workers was also lower than that of normal hearing workers (14.5 ± 5.1 U/ml vs 15.9 ± 6.3 U/ml, P = 0.010). CONCLUSION:: Our results suggest that GSTM1 polymorphism is associated with susceptibility to NIHL.     

谷胱甘肽-S-转移酶基因多态与原发型肝癌的Meta分析

目的：探索谷胱甘肽-S-转移酶（GSTM1、GSTT1、GSTP1）基因多态与原发型肝癌遗传易患性的关系。方法：采用Meta分析方法对国内外1994--2004年关于谷胱甘肽-S-转移酶基因多态与原发型肝癌易患性的研究文献进行综合定量分析。结果：共收集相关文献18篇，累计病例1407例，对照2044例。GSTM1空白基因型可能与原发性肝癌有关，OR值为1．40（95％CI：1．22-1．62）；GSTM1和GSTT1中至少有一个空白基因型的OR值为2．05（95CI：％1．14-3．67），亦提示可能与原发型肝癌的遗传易患性有关；而GSTT1空白基因型、GSTP1突变基因型未显示与原发型肝癌相关，合并的OR值分别为1．13（95％CI：0．77-1．65）和0．68（95％CI：0．47～0．99）。结论：谷胱甘肽-S-转移酶基因多态与原发性肝癌遗传易患性的关系各有不同，GSTM1单项空白基因和GSTM1、GSTT1混合空白基因与原发性肝癌有统计学联系，可能是原发性肝癌的易患因素；GSTT1空白基因型与原发性肝癌未显示有统计学联系，而GSTP1的突变基因型可能是原发性肝癌的保护因素。     

Association of caffeine intake and CYP1A2 genotype with ovarian cancer

Coffee and caffeine consumption has been associated with ovarian cancer risk in several epidemiological studies. CYP1A2 is a key enzyme in the metabolism of coffee and in the activation of heterocyclic aromatic compounds that may be carcinogenic. Data from a preliminary investigation conducted in Hawaii of 164 epithelial ovarian cancer cases and 194 controls were used to examine the hypothesis that coffee and caffeine intake increases the risk of ovarian cancer and that these relations are modified by the CYP1A2 high-inducibility A/A genotype. A personal interview and blood specimen were collected in the subjects' homes. A significant positive trend (p = 0.02) in the odds ratios (ORs) was found with increasing intake of caffeine but not with tea or soda. Regular coffee drinkers were at significantly increased risk (OR = 1.8, 95% confidence interval, CI = 1.1-2.8) of ovarian cancer compared with women who did not drink regular coffee. Women with any CYP1A2 C allele were at similar risk of ovarian cancer (OR = 1.1, 95% CI = 0.7-1.7) compared with women with the A/A genotype. The associations of caffeine and coffee intake with risk were stronger among women with the A/A genotype than among women with any C allele. Somewhat stronger relations of coffee and caffeine intake to risk were found among women with cruciferous vegetable consumption above the median and among cases with mucinous histology. These preliminary data suggest a modest positive association of caffeine and coffee consumption with the OR for ovarian cancer that may be modified by CYP1A2 genotype and exposures, such as cruciferous vegetable consumption, that influence CYP1A2 expression.     

Dietary patterns, food groups and myocardial infarction: a case-control study

Certain dietary patterns may be related to the risk of CVD. We hypothesised that a plant-centred dietary pattern would be associated with a reduced risk of first myocardial infarction (MI). A case-control study of Norwegian men and postmenopausal women (age 45-75 years) was performed. A FFQ was administered, generally within 3 d after incident MI (n 106 cases). Controls (n 105) were frequency matched on sex, age and geographic location. On the FFQ, 190 items were categorised into thirty-five food groups and an a priori healthy diet pattern score was created. We estimated OR using logistic regression with adjustment for energy intake, family history of heart disease, marital status, current smoking, education and age. Among food groups, the risk of MI was significantly higher per SD of butter and margarine (OR 1.66 (95 % CI 1.12, 2.46)), and lower per SD of tomatoes (OR 0.53 (95 % CI 0.35, 0.79)), high-fat fish (OR 0.57 (95 % CI 0.38, 0.86)), wine (OR 0.58 (95 % CI 0.41, 0.83)), salad (OR 0.59 (95 % CI 0.40, 0.87)), whole grain breakfast cereals (OR 0.64 (95 % CI 0.45, 0.90)), cruciferous vegetables (OR 0.66 (95 % CI 0.47, 0.93)) and non-hydrogenated vegetable oil (OR 0.68 (95 % CI 0.49, 0.95)). An abundance of cases were found to have a low a priori healthy diet pattern score. A dietary pattern emphasising nutrient-rich plant foods and high-fat fish and low in trans fatty acids was associated with decreased risk of MI among Norwegians.     

谷胱甘肽转硫酶M1和T1基因型与高原反应的危险性

目的探讨谷胱甘肽转硫酶M1、T1基因型(GSTM1、GSTT1)与高原反应危险性的关系。方法从同一生活和工作环境中选取123名男性武警战士作为调查对象，根据是否发生急性高原反应，将其分成病例组和对照组，其中病例组43人、对照组80人。基因组DNA来自研究对象提供的外周血有核细胞，采用多重聚合酶链反应(17CR)方法对这些武警战士的谷胱甘肽转硫酶M1和T1基因进行分型。结果病例组GSTT1非缺失型基因频率为69．8％，明显高于正常对照组(42．5％)，差异有统计学意义(P=0．004，OR=3．12，95％CI为1．42—6．86)。两组GSTM1缺失型基因频率分别为72．1％和52．5％，差异有统计学意义(P=0．03，OR=2．34，95％CI为1．05—5．02)。GSTT1阴性／GSTM1阴性基因型者发生高原反应的危险性比携带GSTT1阴性／GSTM1阳性者高5倍(OR=5．04；95％CI为1．00-25．3)。结论谷胱甘肽转硫酶M1、T1基因多态性与高原反应危险性有关。     

Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals

Aims: To investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC).

Methods: One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire.

Results: Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals (OR 2.73; 95% CI 0.91 to 8.22 v 1.14; 95% CI 0.46 to 2.82) or pesticides (OR 3.46; 95% CI 1.12 to 10.74 v 1.59; 95% CI 0.48 to 5.34). The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null.

Conclusions: Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.

     

MPO和GSTM1、GSTT1基因多态性与儿童急性白血病易感性分析

目的 探讨髓过氧化物酶（myeloperoxidase,MPO）和谷胱甘肽S-转移酶（glutathione S-transferase,GST） M1、T1基因多态性及其交互作用与儿童急性白血病易感性的关系。方法 155名广东籍儿童急性白血病患者纳入病例组,155健康体检者为对照组。采用巢式聚合酶链式反应检测MPO （G-463A）,GSTT1,GSTM1基因型。采用（口恶）2检验比较各基因型频率在病例组与对照组之间的差异,用OR及95%CI值表示各基因型发生急性白血病的危险度。结果 携带MPO-463位点A突变基因型（GA/AA）可能降低儿童急性白血病发病危险（OR=0.591,95%CI:0.356~0.981,P=0.041）;同时携带GSTT1 null基因和GSTM1 null基因的个体发生发生急性白血病的危险性是同时携带GSTT1 non-null基因和GSTM1non-null基因个体的2.991倍（95%CI:1.578~5.673）;同时携带MPO野生型（GG）基因及GSTT1 null基因和GSTM1 null基因进一步增加发病危险（OR=3.484,95%CI:1.626~7.466,P=0.041）。结论 同时携带MPO野生型（GG）及GSTT1 null基因和GSTM1 null基因的个体发生急性白血病的风险增大,可考虑作为儿童急性白血病易感性的重要生物标志物。     

中国汉族人口三种谷胱甘肽S-转移酶基因多态性分析

目的：分析中国汉族人口谷胱甘肽S－转移酶（GSTs)基因多态性分布。方法：样本为450名中国汉族人口,采用多重等位基因特异聚合酶链反应（PCR）方法分析GSTM1和GSTT1基因多态性,采用PCR－限制性片段长度多态性方法分析GSTP1＋313核苷酸位点的基因多态性。结果：GSTM1缺失型和GSTT1缺失型基因型频率分别为57％和45％,同时具有GSTM1缺失型和GSTT1缺失型基因型的人个体频率为28．92％;而GSTP1＋313位点G等位基因频率为18．7％,并发现该人群中同时具有3种危险基因型（GSTM1缺失型、GSTT1缺失型和GSTP1＋313A／A）的个体频率为18．04％。GSTs基因型分布不受性别和年龄的影响。结论：中国汉族人口GSTM1、GSTT1和GSTP1基因呈多态性分布,其等位基因和基因型频率不同于其他种族。     

GSTM1, GSTT1, GSTP1, and GSTA1 polymorphisms and urinary isothiocyanate metabolites following broccoli consumption in humans

Isothiocyanates (ITC) are potentially anticarcinogenic phytochemicals formed from the metabolism of glucosinolates and are found in cruciferous vegetables as well as a select number of other foods. ITC are both substrates for and inducers of glutathione S-transferase (GST) phase II metabolizing enzymes involved in carcinogen detoxification as well as effectors of phase I pathways. Previous studies report mixed results on the interaction between cruciferous vegetable intake, GST polymorphisms, and risk of cancer. We conducted a study of 114 healthy human subjects between 18 and 50 y of age to examine the biologic mechanism underlying the associations, specifically, to assess whether GST genotype is associated with urinary ITC metabolites following a known dose of broccoli. After 48 h of abstaining from all sources of glucosinolates, participants provided a blood sample, consumed 1 meal containing 2.5 g broccoli/kg body weight, and collected urine for 24 h. ITC metabolites were measured in the urine using a HPLC cyclocondensation assay. DNA was extracted from blood samples, and GSTM1 deletion, GSTT1 deletion, GSTP1 Ile105Val, and GSTA1*A/*B were genotyped by matrix-assisted laser desorption/ionization time-of-flight. A chi-square test was used to compare high and low ITC excretion levels across genotypes. ITC levels were regressed on genotype, adjusting for gender. There were no substantial differences in ITC levels among genotypes, either individually or in combination. Contrary to our hypothesis, a higher proportion of GSTM1 null individuals had high ITC excretion (62%) compared with the proportion of GSTM1 present with high ITC excretion (39%) (P = 0.03). These results are in agreement with another feeding study, and lend support to the idea of alternative routes of ITC metabolism.