Serum liver function profiles in coking workers

Coking workers are regularly exposed to coke oven emissions (COE), which consist mainly of polycyclic aromatic hydrocarbons and volatile organic compounds. In a previous cross-sectional study, we found that coking and by-product workers with heavy exposure to COE in the older of two coke operation areas in Taiwan had higher serum activities of hepatic aminotransferase than the controls. In this study, we further examine the relationship of exposure to COE with liver function profiles in coking workers. Liver function profiles included serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL). The exposed group included 88 workers working 3 months or more in the older coke oven plant. Fifty-nine referents, not visiting the coke operation areas in the last 3 months, came from the administrative area in the same company. Each participant wore a personal monitor that was used to measure benzene soluble fraction (BSF) of total particulates, as a surrogate of COE, for 3 consecutive days between August 1995 and February 1996. Serum liver function profiles, hepatitis B surface antigens, and anti-hepatitis C antibodies were examined in the morning following the exposure measurements. Exposure levels were categorized by exposure situations (high, medium, low) among coking workers. The high exposure group (n = 23) worked topside of the oven. The medium exposure group (n = 44) worked at the sideoven for more than 4 hr/day, whereas the low exposure group (n = 21) worked at the sideoven for less than 4 hr/day and mostly remained in the control rooms. The low exposure group was used as an internal comparison group. The median BSF concentrations for various exposure situations were as follows, high exposure group: 372 μg/m³, medium exposure group: 61 μg/m³, low exposure group: 49 μg/m³, and referents: 10 μg/m³. The coking workers (n = 88) did not significantly differ from the referents (n = 59) in any of the liver function profiles. Excluding the referents, workers in the high exposure group had a mean AST level that was 31% higher (95% confidence interval (CI) = 9–57%) and a mean ALT level that was 46% higher (95%CI = 7–98%) than those in the low exposure group after adjusting for appropriate confounders in multivariate models. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/L or ALT > 39 IU/L) was more common in the high exposure group than in the low exposure group (adjusted odds ratio = 4.4; 95% CI = 0.9–22.6). However, these associations were not found in GGT, ALP, or BIL. After controlling for the possible effects of nonoccupational factors on serum activity of AST and ALT, we conclude that increased AST and ALT levels among topside coking workers may be caused by heavy inhalation exposure to COE. Additionally, the adverse hepatic effect seems to be caused by a mixture of hazards, rather than a unique identifiable chemical. Am. J. Ind. Med. 32:478–486, 1997. © 1997 Wiley-Liss, Inc.     

某焦化厂职业接触多环芳烃焦炉工肝脏某些酶活性的变化

目的探讨多环芳烃(PAHs)对炼焦作业工人某些肝血清酶活性改变的可能影响。方法对乙肝表面抗原(HBsAg)阴性的炼焦作业工人和非PAHs职业接触工人进行总PAHs累积接触指数(CEL-PAHs)评估,尿中1-羟基芘(1-OHP)浓度等级划分,和血清中丙氨酸转移酶(ALT)、天门冬氨酸转移酶(AST)、γ-谷氨酰转移梅(GGT)、碱性磷酸酶(ALP)的检测。结果焦炉工职业性PAHs暴露水平明显高于对照组(P<0·05)。与对照组相比,血清ALT的明显升高可见于CEL-PAHs<50μg/(m3·a)组和尿中1-OHP浓度<2·3μmol/mol肌酐CEL-PAHs≥200μg/m3组,血清AST的明显升高可见于CEL-PAHs<50μg/(m3·a)组;当CEL-PAHs(200μg/(m3·a)或尿中1-OHP浓度≥10·0μmol/mol肌酐时,可发现四种肝生化指标实测值的明显升高(P<0·05),以及ALT、AST和GGT异常率的明显升高(P<0·05),以血清GGT水平的升高(10倍CEL-PAHs的上升导致1·24倍血清GGT水平的升高,10倍尿中1-OHP浓度的上升导致1·19倍的升高)和异常率的上升(logistic回归,调整OR值为6·2~7·2,P<0·05)最为明显。结论PAHs职业暴露可导致炼焦作业工人肝脏某些血清酶活性的升高。     

焦炉工职业性多环芳烃暴露特征的研究

目的 探讨焦炉工职业性多环芳烃暴露特征。方法 个体采样、高效液相色谱法测定作业环境中多环芳烃含量,以分析焦炉工职业暴露特征,并引入毒性当量因子概念,评价焦炉工职业性多环芳烃暴露的致癌潜能。结果 焦化厂炉顶工多环芳烃职业暴露水平明显高于炉侧工和炉底工,差异有统计学意义(P<0.05);焦炉工多环芳烃职业暴露中非致癌性物质所占比例>70％,致癌性物质中苯并(a)芘(B[a]Py)占总B[a]Py等当量浓度的65.5％-72.4％;多环芳烃职业暴露总量和B[a]Py及芘含量呈正相关(r2分别为0.84和0.94,P<0.05)。结论 焦炉工职业性多环芳烃暴露水平较高且具有一定的致癌潜能,致癌性物质以B[a]Py为主。     

CYP1A1基因多态性与焦炉工尿中1-羟基芘水平的关系

目的 研究CYPIAl多态性与焦炉工尿中1-羟基芘水平的关系.方法 按照苯并[a]芘(B[a]P)接触水平将223名焦炉工分为炉顶组(76名)、炉侧组(82名)和炉底组(65名),以119名无职业性接触多环芳烃的工人为对照组,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)CYPIAl基因Mspl位点多态性、等位基凶特异性扩增方法 检测CYPlAl基因1462V位点的多态性.结果 炉顶组、炉侧组和炉底组焦炉工尿中1-羟基芘水平分别为(3.77+0.64)、(3.57+0.49)、(3.26+0.80)μmol/mol Cr,明显高于对照组,差异有统计学意义(PO.05).炉侧组和炉顶组CYPIAl 1462V位点的各基因型尿中1-羟基芘水平均为Ⅱe/Ⅱe<Ⅱe/Val相似文献   

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。     

细胞色素P4501A1基因多态性与食管癌易感性关系的Meta分析

目的 探讨细胞色素P4501A1(CYP1A1)MspI和Ile/Val位点基因多态性与食管癌发生的关系.方法 采用Meta分析方法,对国内外1997-2008年采用病例对照方法研究CYP1A1MspI和Ile/Val基因多态性与食管癌发生关系的16篇(MspI 8篇,Ile/Val 14篇)文献,采用显性模型(即突变基因型与野生型比较)进行综合定量分析,然后按病理分型(鳞癌/腺癌)分亚组进行分析.结果 综合分析CYP1A1 MspI突变基因型(TC+CC)与食管癌发生无统计学关联(OR=1.17,95%CI:0.82～1.66),亚组分析亦未发现CYP1A1 MspI突变基因型与食管鳞癌(OR=1.17,95%CI:0.82～1.69)和食管腺癌(OR=1.39,95%CI:0.67～2.09)的统计学关联;携带CYP1A1突变基因型(Ile/Val+Val/Val)的个体发生食管癌的危险性是野生型的1.39倍(OR=1.39,95%CI:1.07～1.80);亚组分析显示突变基因型与食管鳞癌发生的易感性相关但与食管腺癌无关联,OR值分别为1.43(95%CI:1.07～1.91)和1.20(95%CI:0.62～2.30).结论 CYP1A1 Ile/Val位点突变基因型可增加食管鳞癌发生的危险性,CYP1A1 MspI位点基因多态性与食管癌无关联.     

The associations between birthweight and adult markers of liver damage and function

Evidence suggesting an effect of fetal growth on liver development and function stems from both animal and human studies. The association of birthweight with adult markers of liver damage and function was examined in a random sample of 2101 British women aged 60-79 years. Age-adjusted natural logged levels of alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) decreased linearly across increasing thirds of birthweight. Alkaline phosphatase (ALP) levels were higher in women of the lowest third of the birthweight distribution compared with other women. No evidence was found for associations of birthweight with aspartate aminotransferase (AST), total bilirubin and albumin. After full adjustment for social class, physical activity, smoking and alcohol consumption, an increase in one standard deviation of birthweight (691 g) was associated with a 2% ([95% CI 0%, 4%], P = 0.021) decrease in the geometric mean of ALT, a 4% decrease in GGT ([95% CI 1%, 6%], P = 0.008) and a 2% decrease in ALP ([95% CI 0%, 3%], P = 0.001). Associations of birthweight with ALT and GGT, but not with ALP, were attenuated when adjusting for components of the metabolic syndrome. These findings suggest that factors affecting intrauterine growth may increase the propensity for adult liver damage. The attenuation of associations with adjustment for components of the metabolic syndrome is in line with non-alcoholic fatty liver disease, indicated by elevated ALT and GGT, being the hepatic manifestation of the metabolic syndrome, and of the influence of perinatal factors on this syndrome.     

微粒体环氧化物水化酶基因多态性对焦炉工尿中1-羟基芘水平的影响

目的　研究外源性化学物代谢酶基因多态性与焦炉工尿中 1 羟基芘水平的关系。方法　分别选取 14 8名焦炉工和 6 9名非职业多环芳烃 (PAHs)暴露人员作为研究对象 ,使用碱水解 -高效液相色谱法测定其尿中 1 羟基芘浓度 ;分析了CYP1A1基因第 7外显子I4 6 2V位点、GSTM1、GSTT1、GSTP1基因I10 5V位点、CYP2E1基因 5’非编码区的Pst1位点和第 6内含子的Dra1位点、NQO1基因P187S位点、NAT2基因Kpn1、BamH1和Taq1位点以及mEH基因H113Y和R139H位点的多态性 ;使用调查表收集个人职业暴露史、年龄、性别、吸烟和饮酒等信息。结果　焦炉工尿中 1 羟基芘水平[(5 .6 1± 1.0 4 ) μmol molCr]高于对照组 [(0 .74± 0 .32 ) μmol molCr],差异有显著性 (P <0 .0 5 )。调整了PAHs外暴露等级和吸烟因素后 ,焦炉工中具有mEH基因 113位点变异纯合子基因型个体尿中1 羟基芘水平高于杂合子和野生型纯合子 (6 .4 1± 1.0 9>6 .2 4± 1.0 9>4 .6 2± 0 .95 μmol molCr) ,且野生型纯合子与变异型纯合子基因型个体间尿中 1 羟基芘水平的差异有显著性 (P <0 .0 5 )。在焦炉工中还发现CYP1A1和mEH基因多态性存在交互作用。结论　mEH基因 113位点的基因多态性可明显影响焦炉工尿中 1 羟基芘水平。     

Urinary 1-hydroxypyrene concentrations in Chinese coke oven workers relative to job category, respirator usage, and cigarette smoking

BACKGROUND: 1-Hydroxypyrene (1-OHP) is a biomarker of recent exposure to polycyclic aromatic hydrocarbons (PAHs). We investigated whether urinary 1-OHP concentrations in Chinese coke oven workers (COWs) are modulated by job category, respirator usage, and cigarette smoking. METHODS: The present cross-sectional study measured urinary 1-OHP concentrations in 197 COWs from Coking plant I and 250 COWs from Coking plant II, as well as 220 unexposed referents from Control plant I and 56 referents from Control plant II. RESULTS: Urinary 1-OHP concentrations (geometric mean, micromol/mol creatinine) were 5.18 and 4.21 in workers from Coking plants I and II, respectively. The highest 1-OHP levels in urine were found among topside workers including lidmen, tar chasers, and whistlers. Benchmen had higher 1-OHP levels than other workers at the sideoven. Above 75% of the COWs exceeded the recommended occupational exposure limit of 2.3 micromol/mol creatinine. Respirator usage and increased body mass index (BMI) slightly reduced 1-OHP levels in COWs (P < 0.1). Cigarette smoking significantly increased urinary 1-OHP levels in unexposed referents (P < 0.005), but had no effect in COWs (P > 0.1). CONCLUSIONS: Chinese COWs, especially topside workers and benchmen, are exposed to high levels of PAHs. Urinary 1-OHP concentrations appear to be modulated by respirator usage and BMI in COWs, as well as by smoking in unexposed referents.     

CYP1A1 gene polymorphisms in modifying the association between passive smoking and primary dysmenorrhea

PURPOSE: This study investigated whether the association between passive smoking exposure and primary dysmenorrhea is modified by two susceptibility genes, cytochrome P450 1A1 (CYP1A1)MspI and CYP1A1HincII. METHODS: We recruited 1645 female textile workers from 1997 to 2000 in Anqing, China, collecting information about passive smoking and status of primary dysmenorrhea and taking blood samples. We analyzed the association of CYP1A1 gene polymorphisms and passive smoking exposure with primary dysmenorrhea using multiple logistic regression. RESULTS: In the passive smoking group, women who had the C/C6235 genotype (odds ratio [OR] = 1.8; 95% confidence intervals [CI] = 1.0-3.3) in CYP1A1MspI and Ile/Ile462 genotype (OR = 2.9; 95% CI = 1.1-7.7) in CYP1A1HincII had increased risk of dysmenorrhea. When stratified by genotype, the adjusted OR of dysmenorrhea was 1.6 (95% CI = 1.2-2.1) for the passive smoking group with the Ile/Ile462 genotype and 1.5 (95% CI = 1.0-2.1) with the C/C6235 genotype, compared with the nonpassive smoking group. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1MspI C/C6235 and HincII Ile/Ile462 genotypes (OR = 2.4; 95% CI = 1.2-4.9). CONCLUSIONS: CYP1A1MspI and HincII genotypes modified the association between passive smoking and primary dysmenorrhea.     

Passive smoking, cytochrome P450 gene polymorphisms and dysmenorrhea

PURPOSE: This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. METHODS: This report includes 1,645 (1,124 no dysmenorrhea, 521 dysmenorrhea) non-smoking and non-drinking newly wedding female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for maternal age, BMI, age of menarche, education, vibration exposure, shift work, noise exposure, pregnancy history, perceived stress and physical laboring stress. RESULTS: In the passive smoking group, women who have C/C6235 genotype (OR = 1.8, 95% CI = 1.0-3.3) in CYP1A1MspI and Ile/Ile462 genotype (OR = 2.9, 95% CI = 1.1-7.7) in CYP1A1HincII was associated with an increased risk of dysmenorrhea. When stratified by women genotype, the adjusted OR of dysmenorrheal was 1.6 (95% CI = 1.2-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95% CI = 1.0-2.1) with C/C6235 genotype, compared to non-passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1C/C6235 (OR = 1.5, 95% CI = 1.0-2.1), and HincII Ile/Ile462 (OR = 1.6, 95% CI = 1.2-2.1), respectively. CONCLUSION: CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea.     

金昌队列单抗HB-s阳性人群肝功酶异常与脂质代谢指标相关性分析

目的 探讨金昌队列单抗-HBs阳性人群肝功酶异常与脂质代谢指标的关系。方法 整群抽取2011年6月～2013年12月进入金昌队列且排除各种肝病史的单抗-HBs阳性者14 467例作为研究对象,通过实验室血清学检测相关酶学及脂质代谢指标。结果 该人群丙氨酸氨基转移酶（alanine aminotransferase,ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase,AST）、谷氨酰转肽酶（gamma-glutamyltransferase,GGT）异常检出率分别为21.35%、17.45%、15.01%,均为男性高于女性（均有P<0.001）。趋势性χ2检验分析显示,随着甘油三酯（triglyceride,TG）、总胆固醇（total cholesterol,TC）、低密度脂蛋白（low density lipoprotein cholesterol,LDL-C）、体质指数（body mass index,BMI）升高,ALT、AST、GGT异常检出率升高（均有P<0.001）;随着高密度脂蛋白（high density lipoprotein cholesterol,HDL-C）升高,ALT、AST、GGT异常检出率下降（均有P<0.001）,具有剂量反应关系。尿酸（uric acid,UA）异常组ALT、AST、GGT异常检出率均高于正常组（均有P<0.001）。结论 金昌队列单抗-HBs阳性人群ALT、AST、GGT异常检出率均为男性高于女性,且与BMI、TG、TC、LDL-C、HDL-C存在剂量反应关系。     

Assessment of coke oven emissions exposure among coking workers

Coking workers are regularly exposed to coke oven emissions, which consist primarily of polycyclic aromatic hydrocarbons and volatile organic compounds. This study measured the workers' exposure to the benzene soluble fraction of total particulates (BSF). The study population consisted of 88 coking workers as an exposure group and 59 referents. Personal breathing-zone samples of BSF and total particulates were taken from all study subjects for 3 consecutive days. The highest BSF concentrations were found among the topside oven workers (geometric mean; range) (microgram/m3): lidman (515; 72-18, 181), tar chaser (432; 51-4334), and larry car operator (185; 55-649). The lowest was 7 micrograms/m3 in the referents. Among the samples at the topside oven 84% exceeded the Occupational Safety and Health Administration standard (150 micrograms/m3 BSF). The percentage of BSF in total particulates varied across job classifications, ranging from 0.3% in wharfmen to 24% in tar chasers. Area sampling indicated that the BSF concentration at the topside area was sixtyfold higher than that at the administrative area, which was approximately 2 km from the coke oven plant.     

炼焦职业暴露工人与对照人群尿中1-羟基芘水平比较

目的比较焦炉工和非职业暴露人群尿中1-羟基芘的不同水平,并探讨可能的各种影响因素.方法 2002年上半年,以某焦化厂265名炼焦作业工人和226名非职业接触对照人群为调查对象,职业接触组收集工作班末尿,对照组收集晨尿.根据环境中多环芳烃监测和调查表评价外暴露因素和可能的混杂因素,采用高效液相色谱法测定尿中1-羟基芘含量,比较两组人群尿中1-羟基芘的不同水平,并分析外暴露等级、吸烟、饮酒、年龄和体重指数的可能影响.结果尿中1-羟基芘浓度呈炉顶工〉炉侧工〉炉底工〉对照的趋势,几何均数依次为13.49、6.56、1.38和0.35 μmol/mol肌酐,差异有统计学意义;各组人群尿中1-羟基芘浓度超标率分别依次为94.81%、84.73%、35.09%和0.88%,差异有统计学意义.对照人群中≥20支/d吸烟组的尿中1-羟基芘水平明显高于不吸烟组,修正几何均数分别为0.47和0.31 μmol/mol肌酐,差异有统计学意义;对照人群中饮酒组的尿中1-羟基芘水平明显低于不饮酒组,修正几何均数分别为0.33和0.47 μmol/mol肌酐,差异有统计学意义.结论焦炉工尿中1-羟基芘水平较高,以炉侧工和炉顶工最为明显,非职业暴露人群尿中1-羟基芘本底水平与吸烟和饮酒因素有关.     

Abnormal liver function in workers exposed to low levels of ethylene dichloride and vinyl chloride monomer

We investigated whether exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) resulted in increased risk of liver damage. Epidemiological information, including occupational, medical, smoking, and drinking history, was obtained by interview from 251 male workers. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were used as indicators of liver damage. Exposure to moderate or low levels of ECD and VCM resulted in a higher risk of developing abnormal ALT levels than did exposure to lower levels of the chemicals. Results were similar for AST. GGT was not associated with EDC or VCM exposure. Combined exposure to EDC and VCM showed a dose-response relationship in association with abnormal ALT levels. We concluded that relatively low concentrations of VCM and EDC cause liver damage.     

苯并(a)芘神经行为毒性与CYP1A1基因多态性的关系

[目的]探讨苯并(a)芘的神经行为毒性及其与CYP1A1基因多态性的关系。[方法]从某钢铁公司焦化厂选择200名健康成年男性焦炉工人为研究对象。采用自行设计的问卷,收集研究对象的一般情况资料以及与本研究相关的基本信息;用WHO推荐的神经行为核心测试组合(NCTB)测试焦炉工神经行为功能。收集研究对象的班后尿和肘静脉血,用高效液相色谱法检测尿中1-羟基芘(1-OhP)的水平;聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析CYP1A1基因3′非编码区MspI位点多态性;等位基因特异性扩增(ASA)方法检测CYP1A1基因第7外显子Ile-Val位点多态性。[结果]MspI位点野生型(m1/m1)、杂合型(m1/m2)、突变型(m2/m2)个体间神经行为功能各指标差异无统计学意义(P>0.05);第7外显子Ile-Val位点野生型(Ile/Ile)、杂合型(Ile/Val)、突变型(Val/Val)个体间上述指标比较,突变型(Val/Val)倒序数字跨度得分低于野生型(Ile/Ile),差异有统计学意义(P<0.05)。[结论]苯并(a)芘可引起接触人群神经行为功能损害,可能与CYP1A1第7外显子Il...     

The associations of physical activity and adiposity with alanine aminotransferase and gamma-glutamyltransferase

The mechanisms linking obesity and inactivity to diabetes mellitus are unclear. Recent studies have shown associations of alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) with diabetes. In a random sample of 3,789 British women aged 60-79 years, the authors examined the associations of obesity and physical activity with ALT and GGT (1999-2001). Both body mass index and waist:hip ratio were independently (of each other, physical activity, alcohol consumption, smoking, and childhood and adulthood social class) positively and linearly associated with ALT and GGT. In adjusted models, a one-standard-deviation increase in body mass index was associated with a 0.46-units/liter (95% confidence interval (CI): 0.16, 0.75) increase in ALT and a 2.14-units/liter (95% CI: 0.99, 3.30) increase in GGT. Similar results for a one-standard-deviation increase in waist:hip ratio were 13.96 (95% CI: 10.44, 17.48) for ALT and 39.44 (95% CI: 25.89, 52.98) for GGT. Frequency of physical activity was inversely and linearly associated with GGT in fully adjusted models, but the inverse association with ALT was attenuated towards the null after adjustment for body mass index and waist:hip ratio. Adjustment for ALT and GGT resulted in some attenuation of the strong linear associations of body mass index and waist:hip ratio with diabetes. These findings provide some support for the suggestion that the relation between obesity and diabetes is, at least in part, mediated by liver pathology.     

Serum polychlorinated biphenyls, cytochrome P-450 1A1 polymorphisms, and risk of breast cancer in Connecticut women

Recent epidemiologic studies have suggested that genetic polymorphisms in the cytochrome P-450 1A1 gene (CYP1A1) may affect the relation between environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk. The authors report results from a case-control study evaluating the potential effect of gene-environment interaction between CYP1A1 and serum PCB levels on breast cancer risk among Caucasian women in Connecticut. The study included 374 case women with histologically confirmed breast cancer and 406 noncancerous controls with information on both serum PCB level and CYP1A1 genotype (1999-2002). Compared with women who had the homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 variant genotype (odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.1, 3.9), especially postmenopausal women (OR = 2.4, 95% CI: 1.1, 5.0). Risks associated with the CYP1A1 m2 variant genotype were highest for all women (OR = 3.6, 95% CI: 1.5, 8.2) and postmenopausal women (OR = 4.3, 95% CI: 1.6, 12.0) with higher serum PCB levels (611-2,600 ng/g). The CYP1A1 m1 and m4 genotypes were not associated with breast cancer risk independently or in combination with PCB exposure. In summary, the CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer and may modify the relation between PCB exposure and breast cancer risk.     

CYP1A1和GSTM1基因多态与肺癌发病关系的病例-对照研究

目的 探讨肺癌易感性标记物CYP1A1及GSTM1基因多态以及吸烟等其他环境暴露因素与肺癌发生的关系。方法 采用病例-对照研究的方法，收集原发性肺癌病例91例以及非肺部疾患的住院病例(对照)91例，所有的研究对象均采静脉血进行DNA抽提，并用PCR方法检测CYP1A1以及GSTM1基因多态，同时调查研究对象吸烟等其他环境暴露因素。应用Logistic回归分析方法进行单因素和多因素的分析。结果 无论是单因素分析还是多因素分析均未显示出CYP1A1和GSTM1基因多态与肺癌发病的关联。多因素分析结果表明：化程度的OR为0．63(95％CI：0．45～0．86)，吸烟量的OR为1．56(95％CI：1．14～2．14)，无抽油烟机的OR为3．77(95％CI：1．48～9．56)，食用动物油的OR为1．67(95％CI：1.25～2．24)，常吃胡萝卜的OR为0．47(95％CI：0．22～0．98)，饮酒的OR为6．58(95％CI：1.53～28．30)，家族肺癌史的OR为3．75(95％CI：1．64～8．58)。结论 CYP1A1和GSTM1基因多态与肺癌发病无明显的关联，吸烟、饮酒、食用动物油、家族肺癌吏以及无抽油烟机是肺癌的危险因素，而高化程度和常吃胡萝卜与降低肺癌风险有关。     

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.