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.     

GSTT1 genotype modifies the association between cruciferous vegetable intake and the risk of myocardial infarction

BACKGROUND: Cruciferous vegetables are a major dietary source of isothiocyanates that may protect against coronary heart disease. Isothiocyanates induce glutathione S-transferases (GSTs), polymorphic genes that code for enzymes that conjugate isothiocyanates, as well as mutagens and reactive oxygen species, to make them more readily excretable. OBJECTIVE: The objective of the study was to determine whether GST genotypes modify the association between cruciferous vegetable intake and the risk of myocardial infarction (MI). DESIGN: Cases (n = 2042) with a first acute nonfatal MI and population-based controls (n = 2042) living in Costa Rica, who were matched for age, sex, and area of residence, were genotyped for a deletion polymorphism in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. Cruciferous vegetable intake and smoking status were determined by questionnaire. Odds ratios (ORs) and 95% CIs for MI were estimated by unconditional logistic regression. RESULTS: Compared with the lowest tertile of cruciferous vegetable intake, the highest tertile was associated with a lower risk of MI among persons with the functional GSTT1*1 allele (OR: 0.70; 95% CI: 0.58, 0.84) but not among those with the GSTT1*0*0 genotype (OR: 1.23; 95% CI: 0.83, 1.82) (P = 0.006 for interaction). This protective effect among those with the GSTT1*1 allele was greater for current smokers (OR: 0.54; 95% CI: 0.36, 0.79) than for nonsmokers. GSTP1 and GSTM1 did not modify the association between cruciferous vegetable intake and MI. CONCLUSIONS: Consumption of cruciferous vegetables was associated with a lower risk of MI among those with a functional GSTT1*1 allele, which suggests that compounds that are detoxified by this enzyme contribute to the risk of MI.     

Glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a HuGE review and meta-analysis

The association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and oral cancer is not consistent across studies, and data on their interaction with smoking in oral cancer are lacking. The authors systematically searched PubMed and SciVerse Scopus for case-control studies examining the association between null genotypes of the GSTM1 and GSTT1 genes and oral cancer. Twenty-eight case-control studies published in English were identified. Summary odds ratios were derived via random-effects models. The summary odds ratio for the GSTM1 null genotype was 1.43 in Asians (95% confidence interval (CI): 1.14, 1.78; P < 0.01, I (2) = 73%) and 0.98 in Caucasians (95% CI: 0.76, 1.28; P = 0.91, I (2) = 0%). Case-only analysis of 6 studies (552 cases) showed an inverse multiplicative interaction between GSTM1 null polymorphisms and smoking (ever/high levels of smoking vs. never/low levels) (odds ratio (OR) = 0.51, 95% CI: 0.32, 0.82; P = 0.01, I (2) = 34%). The GSTT1 null genotype was not significantly associated with oral cancer in Asians (OR = 1.07, 95% CI: 0.82, 1.38; P = 0.63, I (2) = 65%) or Caucasians (OR = 1.04, 95% CI: 0.41, 2.65; P = 0.93, I (2) = 55%). In conclusion, the GSTM1 null genotype may be associated with a higher risk of oral cancer in Asians but not in Caucasians, and this effect may be modified by smoking status. The GSTT1 null genotype may not be associated with oral cancer.     

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。     

谷胱甘肽转硫酶M1和T1基因型与食管癌危险性:病例-对照研究

为探讨参与致癌物代谢的谷胱甘肽转硫酶（ＧＳＴ）Ｍ１和Ｔ１基因多型性与食管癌危险性的关系，以病例－对照分子流行病学方法，分析食管癌高发区河南林县的食管癌、食管上皮重度增生病例和性别、年龄配对的正常对照者（各４５例）的ＧＳＴＭ１和ＧＳＴＴ１基因型分布的差异。基因组ＤＮＡ来自研究对象的食管外科手术标本或细胞学检查获得的食管上皮细胞，以多重聚合酶链反应方法进行基因分型。结果：食管癌、食管上皮重度增生病例和     

Urinary Isothiocyanates Level and Liver Cancer Risk: A Nested Case-Control Study in Shanghai,China

Experimental studies have provided evidence that isothiocyanates (ITCs) from cruciferous vegetables may modulate carcinogen metabolism and facilitate carcinogen detoxification and reduce cancer risk. However, no epidemiological studies on liver cancer were reported. This study investigates the association between urinary ITCs levels and liver cancer risk among men and women in Shanghai, China. A nested case-control study of 217 incident cases of liver cancer and 427 matched controls identified from the Shanghai Women's Health Study and Shanghai Men's Health Study was conducted. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) summarizing the association between urinary ITCs levels and liver cancer risk. Compared to those with undetectable ITCs, nonsignificantly inverse association was observed among detectable (OR = 0.80; 95% CI = 0.51–1.26), below-median (OR = 0.76; 95% CI = 0.47–1.24), and above-median concentration (OR = 0.86; 95% CI = 0.52–1.41) with liver cancer risk. Similar patterns were observed when urinary ITCs levels were categorized into tertiles or quartiles. Although our study firstly focused on the association between urinary ITCs exposure and liver cancer risk, we did not find significant results. Future multicenter prospective, different population studies are warranted to validate our findings.     

Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a multicenter, hospital-based case-control study in Japan

We assessed the possible association of gastrointestinal cancers with cruciferous vegetables and mushrooms in a multicenter, hospital-based case-control study in an agricultural area of Japan. One hundred forty-nine cases and 287 controls for stomach cancer and 115 cases and 230 controls for colorectal cancer were matched by age, sex, and residential area. In stomach cancer, the protective effect of vegetables (consumption of total vegetable) was obscure, but it became clearer when we examined specific kinds of vegetables. Marginal associations were observed in the group of the highest consumption of Chinese cabbage (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.35-1.07), broccoli (OR = 0.60; 95% CI = 0.34-1.08), Hypsizigus marmoreus (Bunashimeji) (OR = 0.57; 95% CI = 0.31-1.04) and Pholita nameko (Nameko) (OR = 0.56; 95% CI = 0.30-1.06). In colorectal cancer, we observed decreased risks from the highest tertile of total vegetables (OR = 0.22; 95% CI = 0.08-0.66) and low-carotene-containing vegetables (OR = 0.28; 95% CI = 0.08-0.77), and inverse associations were observed in the group of the highest consumption of broccoli (OR = 0.18; 95% CI = 0.06-0.58). Although the sample size was limited, subgroup analyses showed that the associations differed with the histopathological subtype. These findings suggest that cruciferous vegetables decrease the risk of both stomach and colorectal cancer, and that mushrooms are associated with a decreased risk of stomach cancer.     

谷胱甘肽转硫酶M1、T1基因型及烟酒嗜好与胃癌易感性的关系

[目的]探讨谷胱甘肽转硫酶基因多态性M1（GSTM1）、T1（GSTT1）及烟酒嗜好与胃癌易感性的关系，并对GST基因多态性GSTT1、GSTM1与烟酒暴露在胃癌发生中的交互作用进行分析。[方法]采用1：1配对病例-对照研究方法和PCR技术，检测121例原发性胃癌患者和相应对照的GSTM1和GSTT1基因型，结合研究对象的烟酒嗜好，应用SAS统计分析系统，分析GSTM1和GSTT1基因型及烟酒暴露与胃癌发病的关系，并对基因-基因，基因-烟酒暴露在胃癌发生中的交互作用进行分析。[结果]GSTM1（-）基因型频率在病例组和对照组中分别占44．63％和33．88%，分布无显著性差异（χ^2=2．6436，P〉0．05），GSTT1（-）基因型频率在病例组和对照组中分别为52．89％和44．63名，分布也无显著性差异（χ^2=1．1650，P〉0．05）。吸烟者比非吸烟者发生胃癌的危险高（OR=2．538，95％CI：1．336～4．823）；饮酒者比非饮酒者发生胃癌的危险高（OR=2．097，95％CI：1．025～4．291）。同时携带GSTM1（-）和GSTT1（-）基因型者发生胃癌的危险性高于GSTM1（＋）和GSTT1（＋）基因型携带者（OR=2．097，95％CI：1．025～4．291）；同时有烟酒嗜好的个体发生胃癌的危险性高于无烟酒嗜好者（OR=2．330，95％CI：1．211～4．482）。携带GSTM1（-）和GSTT1（-）且有烟酒嗜好者，发生胃癌的危险显著高于携带GSTM1（＋）和GSTT1（＋）的无烟酒嗜好者（OR=3．600，95％CI：1．025～12．650）。[结论]吸烟、饮酒与胃癌易感性增加有关，GSTM1和GSTT1基因型及烟酒嗜好在胃癌发生中存在一定的交互作用。     

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。     

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.     

Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis

OBJECTIVE: In a nested case-control study, the authors investigated whether the deletion polymorphism of glutathione S-transferases GSTM1 and GSTT1 represents a risk factor for the development of asbestosis. METHODS: In total, 262 cases with asbestosis and 265 controls, selected from a cohort of 2080 workers occupationally exposed to asbestos, were genotyped for GSTM1 and GSTT1-null alleles. Cumulative exposure for each subject was available. RESULTS: Asbestosis was associated with cumulative exposure (odds ratio [OR]=3.21, confidence interval [CI] 2.43-4.23) and GSTT1-null genotype (OR=0.61, CI 0.40-0.94), but not with GSTM1-null genotype (OR=1.01, CI 0.71-1.43). The risk of GSTM1-null and GSTT1-null genotype for asbestosis did not change after adjustment by cumulative exposure, smoking, gender, and age. CONCLUSIONS: An important finding of this study is that GSTT1 gene deletion might have a protective effect on the development of asbestosis.     

Cigarette smoking and colorectal cancer: APC mutations, hMLH1 expression, and GSTM1 and GSTT1 polymorphisms

The contribution of cigarette smoking to sporadic colorectal cancer may differ according to molecular aspects of the tumor or according to glutathione S-transferase M1 (GSTM1) or glutathione S-transferase T1 (GSTT1) genotype. In the prospective Netherlands Cohort Study on Diet and Cancer, adjusted incidence rate ratios for 1986-1993 were computed for overall colorectal cancer, tumors with and without adenomatous polyposis coli (APC) mutations, and tumors with and without human mut-L homologue 1 (hMLH1) expression, according to cigarette smoking characteristics (661 cases, 2,948 subcohort members). Case-only analyses were performed to estimate odds ratios for interaction between cigarette smoking and GSTM1 and GSTT1 genotypes. In comparison with never smokers, a high smoking frequency increased the risk of colorectal cancer (for a five-cigarette/day increment, incidence rate ratio (IRR) = 1.07, 95% confidence interval (CI): 1.03, 1.12), and this association was stronger in 371 tumors without a truncating APC mutation (IRR = 1.11, 95% CI: 1.05, 1.17). Long-term smoking was associated with lack of hMLH1 expression in 56 tumors (for a 10-year increment, IRR = 1.17, 95% CI: 1.00, 1.37). No statistically significant interactions between smoking and GSTM1 or GSTT1 genotype were observed. These results indicate that cigarette smoking is associated with risk of colorectal cancer, and this association may depend on molecular characteristics of the tumor as defined by APC mutation and hMLH1 expression status.     

NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒的遗传易感性

目的探讨NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒遗传易感性之间的关系。方法选择100名慢性苯中毒病例为病例组及90名同期接苯但无苯中毒表现的同工种工人为对照组,应用PCR-RFLP及多重PCR方法判定NQO1、GSTT1和GSTM1基因型。结果携带NQO1C609TT/T基因型(纯合突变型)个体发生苯中毒的危险性是具有C/T基因型(杂合型)和C/C基因型(野生型)个体的2.82倍(95%CI1.42～5.58,P<0.05),是具有C/C基因型(野生型)个体的2.94倍(95%CI1.25～6.90,P<0.05);携带GSTT1缺失(null)基因型个体发生苯中毒的危险性是具GSTT1非缺失(non-null)基因型个体的1.91倍(95%CI1.05～3.45,P<0.05),未发现GSTM1基因型与苯中毒的关系。同时携带NQO1C609TT/T基因型、GSTT1缺失、GSTM1缺失任何两种基因型的个体发生苯中毒的危险性均高于同时携带野生型及非缺失基因型的个体;并且同时携带NQO1C609TT/T基因型、GSTT1缺失与GSTM1缺失个体接苯时发生苯中毒的危险性最高,是NQO1C609TC/T基因型和C/C基因型、GSTT1非缺失型(non-null)与GSTM1非缺失型(non-null)个体的20.41倍(95%CI3.79～111.11,P<0.01)。结论基因之间的交互作用在苯中毒的发生中起重要作用。同时携带NQO1C609TT/T基因型、GSTT1缺失基因型和GSTM1缺失基因型个体发生苯中毒的风险最     

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.

     

Influence of GSTT1 null genotype on the offspring sex ratio of gasoline filling station workers

The aim of this study was to investigate whether the occupational exposure to gasoline of men employed at filling stations affects the sex of their children. Altogether 115 offspring (47 males, 68 females) were identified within families of 49 men working in filling stations in Shiraz (Fars province, south of Iran) and 345 offspring (178 males, 167 females) from 147 families of unexposed persons from the general population of Shiraz, which were matched by age of fathers (+/-2 years) and number of children as a control group. The offspring sex ratio at birth (male proportion) in the filling station workers was significantly lower than the ratio in control group (OR = 0.65; 95% confidence intervals (CI) 0.42 to 0.99). Genotypes of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) were investigated on extracted genomic DNA of 37 exposed workers using the polymerase chain reaction based method. In exposed group with active GSTM1 and GSTT1 genes, offspring sex ratio was the same as the ratio in the control group (OR = 0.66; 95% CI 0.34 to 1.28). However, in the exposed group with active GSTM1 and null genotype of GSTT1, the offspring sex ratio statistically decreased (OR = 0.45; 95% CI = 0.21 to 0.96). It seems that the GSTT1 null genotype has an effect on offspring sex ratio in the filling station workers.     

代谢酶基因多态性与结直肠癌的易感性

目的研究代谢酶细胞色素P450（cytochrome P450s,CYP）1A1、谷胱甘肽转移酶（glutathione—S-transferase,GST）M1和T1、尿苷二磷酸葡萄糖醛酸转移酶（UDPglucumnosyltransferase,UGT）1A7基因多态性与结直肠癌的易感性及其交互作用。方法2002年5月在浙江省嘉善县开展的现场病例对照研究及单纯病例研究,获得140例结直肠癌患者和343名健康对照,用PCR-限制性片段长度多态性等方法检测CYP1A1、GSTM1、GSTT1和UGT1A7的基因多态,并应用非条件logistic回归方法进行数据分析。结果CYPIA1 MspI多态（非编码区T6235C）C／C基因型、T／C和C／C基因型者相对于T／T基因型者的OR值分别为0．493（95％CI：0．254—0．956）和0．638（95％CI：0．427—0．952）,具有统计学意义;GSTM1、GSTT1非缺陷型与缺陷型的分布频率对照组和病例组比较差异无统计学意义;对照组和病例组UGT1A7变异／变异型基因与野生纯合型基因比较差异有统计学意义（OR=2．501,95％CI：1．456—4．296）。单纯病例研究分析,CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用,COR值分别为2．617（95％CI：1．015—6．752）和3．935（95％CI：1．323—11．706）;而CYPlAl与GSTM1、CYP1A1与UGT1A7之间无交互作用。结论CYP1A1 MspI变异型可降低机体对结直肠癌的易感性,而UGT1A7的变异／变异基因型可增加结直肠癌的罹患风险,CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用。     

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.     

GSTM1及GSTT1基因多态性与宫颈癌关系的研究

目的：探讨GSTM1及GSTT1基因多态性与宫颈癌发生的关系.方法：采用以医院为基础的病例对照及分子流行病学研究方法,应用多重PCR技术检测125例宫颈癌病例和125例子宫肌瘤对照的GSTM1和GSTT1基因型.结果：病例组GSTM1基因纯合缺失率为58.4%,显著高于对照组43.2%（x^2=5.777,P=0.016）;GSTT1基因纯合缺失率在病例组和对照组分别为53.6%和44.0%,差别无统计学意义（x^2=2.305,P=0.129）;GSTM1和GSTT1联合缺失者患宫颈癌的危险性是两基因同时存在者的2.588倍（95%CI=1.285～5.212）.结论：GSTM1基因纯合缺失或GSTM1、GSTT1联合缺失可能与宫颈癌的发生有关.     

Intakes of selected nutrients, foods, and phytochemicals and prostate cancer risk in western New York

A number of epidemiological studies have suggested that diet may affect the etiology of prostate cancer, but few have investigated the impact of phytochemical intakes on this cancer. We conducted a case-control study of diet and prostate cancer in western New York involving 433 men with primary, histologically confirmed prostate cancer and 538 population-based controls, frequency matched to cases on age and county of residence. Diet was assessed with a detailed food-frequency questionnaire. We calculated daily intakes of nutrients and the phytochemicals beta-sitosterol, campesterol, stigmasterol, total phytosterols, total lignan precursors, quercetin, and kaempferol based on published food composition data. Odds ratios (ORs) and 95% confidence intervals (CIs) describing the association of prostate cancer risk with selected nutrients, phytochemicals, and food groups were estimated with unconditional logistic regression. Compared with men in the lowest quartile of intake, reduced risks were observed for men in the highest quartile of intake of vitamin C (OR = 0.49; 95% CI = 0.33-0.74), beta-carotene (OR = 0.53; 95% CI = 0.36-0.79), alpha-carotene (OR = 0.67; 95% CI = 0.47-0.97), lutein (OR = 0.55; 95% CI = 0.37-0.81), lycopene (OR = 0.62; 95% CI = 0.42-0.92), total lignan precursors (OR = 0.66; 95% CI = 0.47-0.94), quercetin (OR = 0.64; 95% CI = 0.44-0.92), and total vegetables (OR = 0.53; 95% CI = 0.36-0.79), but weak increased risks were observed for snacks and sweets (OR = 1.46; 95% CI = 0.95-2.23). Estimates associated with nutrients and phytochemicals were attenuated after adjustment for total vegetable intake. Nevertheless, our results support the hypothesis that a phytochemical-rich, plant-based diet is of importance in reducing risks of hormone-related neoplasms.     

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.