中国人群GSTM1基因多态性与肺癌易感性的Meta分析

[目的]探讨中国人群中谷胱甘肽S-转移酶（GSTM1）基因多态性与肺癌易感性的关系。[方法]在Pubmed数据库、CNKI数据库、万方数据库、中国生物医学文献数据库（CBM）中查询文献,时间范围从各数据库建库至2014年5月。采用RevMan 5.1和SAS 9.1.3软件对国内外关于GSTM1基因多态性与肺癌易感性的研究进行合并效应值估计和异质性分析。[结果]37篇文献最终被纳入本次研究。Meta分析结果显示：GSTM1缺失基因型的中国人群患肺癌的风险明显增高（OR=1.45,95%CI：1.30～1.62）。亚组分析发现吸烟与非吸烟的中国人群中GSTM1缺失基因型患肺癌的风险分别为对照组的1.69倍（95%CI：1.39～2.07）和1.46倍（95%CI：1.17～1.82）。在病理类型的亚组分析中,GSTM1缺失基因型的中国人群患鳞状细胞肺癌的风险明显高于对照组（OR=1.35,95%CI：1.13～1.61）。[结论]GSTM1缺失基因型增加中国人群患肺癌的发病风险。     

CYP1A1和GSTM1基因多态性与内蒙古人群肺癌易感性的关系

背景与目的 肺癌是严重危害人类健康的恶性肿瘤之一，其发病与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4501A1（CYP1A1）基因多态性和谷胱甘肽硫转移酶M1（GSTM1）基因多态性与内蒙古人群肺癌易感性的关系。方法 用PCR-RFLP技术分析了原发性肺癌组和住院对照组（各163例）的CYP1A1、GSTM1基因的多态性、基因型分布频率和交互作用。结果 CYP1A1突变型和GSTM1基因缺陷型EGSTM1（-）]频率分布分别为36．8％、65．0％（病例组）和19．0％、48．9％（对照组），二者经χ^2检验差异有显著性（χ^2=12．82，P=0．000；χ^2=9．78，P=0．002）。CYP1A1突变型患肺癌的风险显著增加（OR=2．48，95％CI为1．51～4．08）。GSTM1（-）者患肺癌的风险也显著增加（OR=2．03，95％CI为1．30～3．17）。基因突变的协同分析发现CYP1A1突变型／GSTM1（-）在肺癌组和对照组中的分布频率分别为28．8％和8．0％，二者经χ^2检验有显著性差异（χ^2=23．883，P=0．000）。CYP1A1突变型／GSTM1（-）患肺癌的风险显著增加（OR=4．90，95％CI为2．50～9．83）。无论是在肺癌组还是在对照组，CYP1A1突变型／GSTM1（-）和CYP1A1非突变型／GSTM1（-）在性别间分布频率的差异均无显著性（肺癌组χ^2=0．797，P=0．372；对照组χ^2=0．670，P=0．761）。吸烟与肺癌易感性的统计学分析，结果显示吸烟与肺癌易感性有关（χ^2=14．197，P=0．000），吸烟者患肺癌的风险显著增加（OR=2．33，95％CI为1.50～3．62）。CYP1A1突变型与吸烟关系的协同分析发现，携带CYP1A1突变型基因的吸烟者较携带CYP1A1突变型基因不吸烟者易患肺癌（OR=4．44，95％CI为2．40～8．32，χ^2=23．843，P=0．000）。GSTM1（-）与吸烟关系的协同分析中也发现，携带GSTM1（-）的吸烟者患肺癌的风险显著增加（OR=7．32，95％CI为3．39～15．50，χ^2=36．708，P=0．000）。结论 CYP1A1突变型和GSTM1（-）是内蒙古地区肺癌的易患因素，二者对肺癌的发生有协同作用，吸烟与肺癌的易感性也有关，CYP1A1突变型、GSTM1（-）与吸烟在肺癌的发生上也有相互促进作用。     

洛阳市GSTM1和GSTT1缺失基因型与肝癌的遗传易感性

目的探讨肝癌低发区谷胱甘肽转硫酶(GST)M1和T1的缺失基因型与肝癌的关系.方法应用多重PCR技术检测洛阳市95例肝癌患者和103例对照的GSTM1和GSTT1基因型.结果病例组GSTM1缺失基因型的频率为0.705,对照组为0.502,两者差异有显著性(x2=8.28,P=0.004),OR值为2.35(95%CI:1.25～4.41);病例组GSTT1缺失基因型的频率为0.611,对照组为0.437,两者差异有显著性(x2=5.97,P=0.015),OR值为2.02(95%CI:1.10～3.71).叉生分析表明该两因素在肝癌发生中有协同作用(x2=14.83,P=0.002),同时具有两个缺失基因型时,OR值为5.57(95%CI:2.03～15.66);GSTM1和GSTT1缺失基因型均与吸烟有协同作用,OR值分别为5.84(95%CI:2.26～15.47)和5.51(95%CI:2.13～14.54);GSTM1缺失基因型与饮酒有协同作用,OR值为3.31(95%CI:1.47～7.49),而GSTT1缺失基因型与饮酒无协同作用.结论在肝癌低发区GSTM1和GSTT1缺失基因型是肝癌的易感基因型.     

GSTM1、GSTT1基因多态性和吸烟与膀胱癌关系的病例对照研究

目的:应用全人群为基础的病例对照研究探讨GSTM1、GSTT1基因多态性和吸烟与膀胱癌危险性的关系。方法:采用多重PCR方法对404例正常对照和414例膀胱癌病例的基因组DNA进行GSTM1和GSTT1基因分型,应用非条件logistic回归分析方法进行统计分析。结果:与携带GSTM1( )基因型者比,GSTM1(-)基因型的男、女性患膀胱癌危险性分别为1.66(95%CI:1.18～2.33)和1.08(95%CI:0.59～1.98)。同样携带GSTM1(-)基因型,吸烟者比不吸烟者患膀胱癌的危险性更加明显。与不吸烟且携带GSTM1( )基因型男性比,GSTM1(-)基因型的目前吸烟者的OR值为2.99(95%CI:1.56～5.74),而携带GSTM1(-)基因型同时吸烟年限≥40年者OR为4.33(95%CI:2.14～8.73)。尽管女性吸烟例数较少,但携带GSTM1(-)基因型的吸烟女性患膀胱癌危险性显著高于不吸烟的GSTM1( )基因型者,OR值为6.72(95%CI:1.69～26.80)。与不吸烟且携带GSTT1( )基因型男性相比,携带GSTT1(-)基因型的吸烟者患男性膀胱癌危险的OR值为1.38(95%CI:0.79～2.42)。携带GSTT1(-)基因型的吸烟女性患膀胱癌危险性是不吸烟的GSTT1( )基因型者的3.04倍(95%CI:0.77～12.01)。结论:GSTM1(-)基因型能显著增加男性患膀胱癌的风险,该基因型与吸烟可能有一定的联合作用。GSTT1基因型可能与上海市区男、女性膀胱癌无关。     

谷胱甘肽转移酶T1和M1基因多态性及吸烟与结直肠癌关系的对照研究

目的　研究谷胱甘肽转移酶 (GSTs)M1、T1基因多态性与结直肠癌易感性的关系。方法12 6例结直肠癌患者和 343例随机抽样的正常对照者 ,应用多重聚合酶链反应 (PCR)方法检测其GSTM1和GSTT1基因多态性 ,采用非条件Logistic回归模型分析基因型、吸烟情况与结直肠癌患病的关系。结果　GSTM1和GSTT1缺陷型基因型在对照人群中的频率分布为 5 5 .5 %和 2 0 .4 %。在GSTT1缺陷型基因型的人群中 ,GSTM1缺陷型患直肠癌风险是非缺陷型者的 9.74倍 (95 %CI为 1.13～83.85 )。现在吸烟者中 ,GSTM1缺陷型基因型患结肠癌的风险是非缺陷型者的 2 .2 2倍 (P >0 .0 5 ) ;GSTT1缺陷型基因型患结肠癌的风险是非缺陷型者的 4 .5 5倍 (95 %CI为 1.14～ 18.17) ,患直肠癌的风险是非缺陷型者的 4 .6 0倍 (95 %CI为 1.11～ 19.11)。结论　GSTM1和GSTT1缺陷型基因型有可能增加结直肠癌的危险性 ,其危险性主要表现在两者的联合作用上 ;环境暴露因素———吸烟和相关代谢酶多态性也表现出增加结直肠癌危险性的联合作用。     

口腔颌面部恶性肿瘤GSTT1、GSTM1基因多态性改变初步研究

目的探讨谷胱甘态转硫酶M1（GSIM1）和T1（GSTT1）基因型与口腔颌面部恶性肿瘤发生的相关性。方法采用多重PCR技术，对87例口腔颌面部恶性肿瘤病例和与之匹配的对照组87例GSTM1、GsTT1基因型进行检测。结果口腔颌面部恶性肿瘤患者与对照组GSTM1基因缺失频率分别为62．1％和44．8％，差异有显著性（χ^2=5．197，P=0．023），GSTM1基因缺失与口腔颌面部恶性肿瘤易感性有关（OR=2．014，95％CI=1．100～3．688）。GSTM1基因缺失同时暴露于吸烟者患颌面部恶性肿瘤的危险性显著增加（OR=5．477，95％CI=2．257～14．619）。结论GSTM1基因缺失型可能是口腔颌面部恶性肿瘤的易感基因型，GSTM1基因缺失与吸烟在口腔颌面部恶性肿瘤的发生、发展中可能具有协同作用。     

GSTM1和CYP2E1基因多态性与肺癌遗传易感性关系的研究

背景与目的肺癌是中国人群恶性肿瘤死因的首位，其发病可能与肺癌人群中某些肺癌相关基因的遗传多态性有关。本研究旨在探讨细胞色素P4502E1(CYP2E1)基因RsaⅠ／PstⅠ多态性和谷胱甘肽转移酶M1(GSTM1)基因多态性与肺癌易感性之间是否存在相关性。方法应用PCR-RFLP和PCR法检测99例人非小细胞肺癌患者和66例同期住院的肺良性疾病患者CYP2E1基因的RsaⅠ／PstⅠ多态性和GSTM1基因多态性，并分析其与肺癌遗传易感性的相关性。结果(1)CYP2E1基因RsaⅠ／PstⅠ多态性的三种基因型在肺癌组和对照组的频率差异没有统计学意义(χ^2=1．374，P=0．241)。(2)肺癌组GSTM1(-)基因型频率显著高于对照组(分别为57．6％和40．9％)(χ^2=4．401，P=0．036)。(3)携带GSTM1(-)基因型的个体患肺癌的危险性显著高于GSTM1( )基因型的个体(OR=1．96，95％CI=1．042～3．689，P=0．037)。(4)与携带c1／c2或c2／c2基因型的不吸烟个体比较，携带c1／c1基因型的吸烟者患肺癌的风险显著增加(OR=3．525，95％CI=1．168～10．638，P=0．025)。(5)联合分析CYP2E1基因RsaⅠ／PstⅠ多态性和GSTM1基因多态性，携带有c1／c1和GSTM1(-)基因型的个体患肺癌的风险显著高于携带GSTM1( )和c1／c2或c2／c2基因型的个体(OR=3．449，95％CO=1．001～11．886，P=0．050)。按照吸烟因素分层，携带有GSTM1(-)和c1／c1基因型的不吸烟个体患肺癌的风险显著高于携带GSTM1( )和c1／c2或c2／c2基因型的不吸烟个体(OR=11．553，95％CI=1．068-124．944，P=0．044)，携带有GSTM1(-)和c1／c2或c2／c2基因型的不吸烟个体患肺癌的风险同样显著高于携带GSTM1( )和c1／c2或c2／c2基因型的不吸烟个体(OR=13．374，95％CI=1．258～142．166，P=0．032)。结论(1)GSTM1(-)基因型增加人群患肺癌的风险；(2)CYP2E1的c1／c1基因型和GSTM1(-)基因型的联合可增加吸烟和不吸烟人群患肺癌的风险。     

CYP1A1 GSTM1基因多态性和吸烟与肺癌易感性关系的病例对照研究

目的:探讨天津市居民致癌物代谢酶CYP1A1和GSTM1基因多态性对肺癌易感性的影响。方法:利用限制性片断长度多态性-聚合酶链反应(RFLP-PCR)方法检测原发性肺癌患者和健康对照者细胞色素P450酶基因CYP1A1Msp位点和谷胱甘肽硫转移酶基因GSTM1的多态性情况。结果:肺癌组与对照组之间CYP1A1和GSTM1基因型分布差异均存在统计学显著意义(P<0.05)。携带CYP1A1变异基因型或GSTM1阴性基因型的个体患肺癌的危险性增高,比值比(OR)分别达到2.44(1.04～5.81)和1.84(1.03～3.29)。多因素分析结果显示具有CYP1A1变异基因型、GSTM1阴性基因型的吸烟个体患肺癌的风险较大。结论:CYP1A1Msp位点变异基因型和GSTM1阴性基因型可能是肺癌的易感因素,吸烟与肺癌易感基因之间具有协同作用。     

GSTM1、GSTT1基因多态性与四川北部地区肺癌易感性关系的研究

目的:探讨谷胱苷肽硫转移酶M1(GSTM1)和T1(GSTT1)基因多态性与四川北部地区汉族人群肺癌易感性的关系。方法:采用病例对照研究和聚合酶链式反应(PCR)技术检测四川北部地区肺癌病人125例和健康对照组125例中GSTM1(-)和GSTT1(-)的频率,评价两基因型及两基因的交互作用与肺癌易感性的关系。结果:GSTM1(-)在肺癌组和对照组分布频率分别为58.4%和56.8%,单因素回归分析未见统计学差异(OR=1.06,95%CI:0.639-1.757,P=0.822);GSTT1(-)在肺癌组和对照组分布频率分别为45.6%和44.8%,单因素回归分析未见统计学差异(OR=0.968,95%CI:0.588-1.593,P=0.899),GSTM1(-)和GSTT1(-)联合并未增加肺癌风险(OR=1.084,95%CI:0.536-2.192,P=0.823)。结论:GSTM1及GSTT1各基因型单独或联合作用都不是四川北部地区汉族人群肺癌的风险因素。     

细胞色素CYP2E1和GST M1与肺癌易感性的病例对照研究

目的探讨谷胱甘肽转硫酶(GST)和细胞色素CYP2E1多态性与肺癌易感性的关系.方法选取广州市广东籍新发肺癌病人91例及同期非肺部疾患及相同性别的病人91例作匹配,调查他们的吸烟、饮酒等因素的暴露情况.用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测CYP2E1和GST的基因多态性.结果CYP2E1 C1C1基因型与C1C2基因型比较,其OR为1.82(95%CI=0.95～3.40),GSTM1基因缺失型的OR值为1.26(0.69～2.30),而两者联合分析时,则可增加患肺癌的危险,其OR值为2.13(0.82～5.56),但无统计学意义(P＞0.05).吸烟与肺癌关系密切,其OR值为2.82(1.56～5.12),当吸烟与这两种基因型协同作用时,可明显提高患肺癌的危险性,携带CYP2E1 C1C1基因型的吸烟者的OR值为5.42(2.05～14.32),GSTM1基因缺失型的吸烟者的OR值为4.38(1.81～10.61).多因素logistic回归分析结果表明:文化程度(OR为0.63,0.45～0.86)、吸烟量(OR为1.56,1.14～2.14)、元抽油烟机(OR为3.77,1.48～9.56)、食用动物油(OR为1.67,1.25～2.24)、胡萝卜(OR为0.47,0.22～0.98)、饮酒(OR为6.58,1.53～28.3)、直系亲属肺癌史(OR为3.75,1.64～8.58)等因素与肺癌有关,而上述两种基因均未进入模型.结论CYP2E1和GSTM1在单因素分析中未显示出与肺癌风险的联系.这两种基因分别与吸烟协同作用时明显提高肺癌的危险性.然而在多因素分析中均未进入logistic模型,说明它们均不是肺癌个体易感性的主效基因,而是次效基因.     

HDAC1-mSin3a-NCOR1, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a regulate the NY-ESO1 gene expression

The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies. Despite the identification of the epigenetical silencing of the NY-ESO1 gene in a large variety of tumors, the molecular mechanism involved in this phenomenon is not fully elucidated. In two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the NY-ESO1 gene requires the sequential recruitment of the HDAC1-mSin3a-NCOR, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a complexes. Thus, our data illustrate the orchestration of a sequential epigenetic mechanism including the histone deacetylation and methylation, and the DNA methylation processes.     

CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibility

BACKGROUND: In estrogen biosynthetic pathways, many enzymes are important for metabolism, detoxification, and bioavailability. Polymorphisms in these genes may have an effect on the enzymes' function. For example, higher expression and activation of biosynthetic enzymes and lower expression and activation of conjugation enzymes may lead to high toxicity or carcinogenesis. The authors hypothesized that single nucleotide polymorphisms (single nucleotide polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes may be risk factors for endometrial cancer. METHODS: DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG genes. Genotyping was validated by direct DNA sequencing. The authors also investigated the relation between expression of CYP1A1 in endometrial cancer tissues and genotypes of CYP1A1 m1. RESULTS: A decreased frequency of TC + CC genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer patients compared with controls (OR = 0.42; 95% CI, 0.27-0.69). The T-A haplotype of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P = .009). The authors also found that individuals carrying the variants of SULT1A1 codon213 and 2 single nucleotide polymorphisms in the 3' flanking region (14A/G and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C and A-G-T haplotypes of these 3 variants were higher in endometrial cancer patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients. (OR, 4.58; 95% CI, 2.35-8.93). CONCLUSIONS: This is the first report on the combined association of CYP1A1 and SULT gene polymorphisms in endometrial cancer that suggests a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians.     

CYP1A1.

CYP1A1 plays an important role in the metabolism of polycyclic hydrocarbons that occur in the environment and several studies suggest that the genetic polymorphism of the gene may play a role in the predisposition to cancer. In order to evaluate the function of CYP1A1 in vivo as a host factor determinant of environmentally-caused cancers in humans, additional investigations are needed involving not only molecular epidemiological approaches in different ethnic populations but also more direct approaches such as the use of gene-targeted mice as a model system.     

DNA切除修复交叉互补基因1、乳腺癌易感基因、核苷酸还原酶1与非小细胞肺癌

 阐述了近年来非小细胞肺癌（NSCLC）化疗敏感性与DNA 切除修复交叉互补基因1 （ERCC1）、乳腺癌易感基因（BRCA1）、核苷酸还原酶1（RRM1）基因表达关系的研究进展，分析3个基因对NSCLC个体化化疗潜在的指导意义     

Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1

Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) catalyze the oxidative metabolism of 17 beta-estradiol (E2) to catechol estrogens (2-OHE2 and 4-OHE2) and estrogen quinones, which may lead to DNA damage. Catechol-O-methyltransferase catalyzes the methylation of catechol estrogens to methoxyestrogens (2-MeOE2, 2-OH-3-MeOE2, and 4-MeOE2), which simultaneously lowers the potential for DNA damage and increases the concentration of 2-MeOE2, an antiproliferative metabolite. In this study, we showed that CYP1A1 and CYP1B1 recognized as substrates both the parent hormone E2 and the methoxyestrogens. Using purified recombinant enzymes, we demonstrated that CYP1A1 and CYP1B1 O-demethylated the methoxyestrogens to catechol estrogens according to Michaelis-Menten kinetics. Both CYP1A1 and CYP1B1 demethylated 2-MeOE2 and 2-OH-3-MeOE2 to 2-OHE2, whereas CYP1B1 additionally demethylated 4-MeOE2 to 4-OHE2. Because the P450-mediated oxidation of E2 and the O-demethylation of methoxyestrogens both yielded identical catechol estrogens as products, we used deuterated E2 (E2-d4), unlabeled methoxyestrogens, and gas chromatography/mass spectrometry to examine both reactions simultaneously. Kinetic analysis revealed that methoxyestrogens acted as noncompetitive inhibitors of E2 oxidation with K(i) ranging from 27 to 153 micro M. For both enzymes, the order of inhibition by methoxyestrogens was 2-OH-3-MeOE2 > or = 2-MeOE2 > 4-MeOE2. Thus, methoxyestrogens exert feedback inhibition on CYP1A1- and CYP1B1-mediated oxidative estrogen metabolism, thereby reducing the potential for estrogen-induced DNA damage.     

Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer

Polymorphisms in the cytochrome P450 1B1 (CYP1B1) and glutathione S-transferase (GST) drug metabolic enzymes, which are responsible for metabolic activation/detoxification of estrogen and environmental carcinogens, were analyzed for their association with breast cancer risk in 541 cases and 635 controls from a North Carolina population. Each polymorphism, altering the catalytic function of their respective enzymes, was analyzed in Caucasian and African-American women. As reported in previous studies, individual polymorphisms did not significantly impact breast cancer risk in either Caucasian or African-American women. However, African-American women exhibited a trend towards a protective effect when they had at least one CYP1B1 119S allele (OR=0.53; 95% CI=0.20-1.40) and increased risk for those women harboring at least one CYP1B1 432V allele (OR=5.52; 95% CI=0.50-61.37). Stratified analyses demonstrated significant interactions in younger (age < or =60) Caucasian women with the CYP1B1 119SS genotype (OR=3.09; 95% CI=1.22-7.84) and younger African-American women with the GSTT1 null genotype (OR=4.07; 95% CI=1.12-14.80). A notable trend was also found in Caucasian women with a history of smoking and at least one valine allele at GSTP1 114 (OR=2.12; 95% CI=1.02-4.41). In Caucasian women, the combined GSTP1 105IV/VV and CYP1B1 119AA genotypes resulted in a near 2-fold increase in risk (OR=1.96; 95% CI=1.04-3.72) and the three way combination of GSTP1 105IV/VV, CYP1B1 119AS/SS and GSTT1 null genotypes resulted in an almost 4-fold increase in risk (OR=3.97; 95% CI=1.27-12.40). These results suggest the importance of estrogen/carcinogen metabolic enzymes in the etiology of breast cancer, especially in women before the age of 60, as well as preventative measures such as smoking cessation.     

CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure

Certain human biotransformation enzymes have been implicated in the formation and scavenging of the ultimate reactive metabolites, the diolepoxides, from polycyclic aromatic hydrocarbons (PAHs). In the present study, performed on aluminum smelter workers, we have analyzed airborne PAH, the pyrene metabolite 1-hydroxypyrene (1-OHP) in urine, and genotypes for biotransformation enzymes involved in PAH metabolism. The aim was to evaluate the correlation between external exposure and biomarkers of exposure and to investigate to what extent genetic polymorphism in metabolic enzymes can explain interindividual variation in urinary 1-OHP levels. DNA was prepared from blood samples from 98 potroom workers and 55 controls and altogether eight polymorphisms in the CYP1A1, mEH, GSTM1, GSTP1 and GSTT1 genes were analyzed. The 1-OHP excretion was found to correlate significantly (P 100-fold) and univariate and multivariate regression analyses were used to find the variables that could determine differences in excretion. The variation could, to some degree, be explained by differences in exposure to airborne particulate-associated PAHs, the use of personal respiratory protection devices, smoking habits and genetic polymorphisms in the cytochrome P450 1A1, GSTM1 and GSTT1 enzymes. The part of the variance that could be explained by differences in biotransformation genotypes seemed to be of the same order of magnitude as the variance explained by differences in exposure. In the control group as well as in the occupationally exposed group, the highest 1-OHP levels were observed in individuals carrying the CYP1A1 Ile/Val genotype who were also of the GSTM1 null genotype. The results show that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that it may also to some extent reflect the interindividual variation in susceptibility to PAHs.