长链非编码RNA AFAP1-AS1 在胃癌组织中的表达及其临床意义

目的:探讨长链非编码RNA (long non-coding RNA,lncRNA)肌动蛋白纤维相关蛋白-1反义RNA1(actin filament-associated protein 1-antisense RNA1,AFAP1-AS1 RNA1)在胃癌组织中的表达情况及其临床意义.方法:采用Real-time PCR方法检测2010年1月至2014年12月宜昌市第二人民医院及三峡大学仁和医院手术切除的274例胃癌组织及相应癌旁正常胃组织中AFAP1-AS1的表达,并分析AFAP1-AS1表达量与临床及病理特征的关系.结果:AFAP1-AS1在胃癌组织比癌旁正常组织显著高表达(P＜0.01).AFAP1-AS1在早期胃癌组织中平均表达量明显低于进展期胃癌(P＜0.01).在不同病理类型胃癌中,AFAP1-AS1的表达量没有差异(P＞0.05).AFAP1-AS1表达量和胃癌淋巴侵袭或远处转移密切相关,在伴有淋巴结侵袭或远处转移的胃癌组织中,AFAP1-AS1明显高表达(P＜0.01).结论:AFAP1-AS1可能是胃癌发生发展的一个重要因素;有望成为新的胃癌预后标志物,用于胃癌的临床诊断和预后判断.     

AGAP2-AS1在非小细胞肺癌组织中的表达及临床意义

目的 探讨AGAP2反义RNA1(AGAP2-AS1)在非小细胞肺癌(NSCLC)组织中的表达及临床意义。方法回顾性分析95例NSCLC患者临床资料,收集患者NSCLC组织及癌旁正常组织。采用实时荧光定量PCR法测定NSCLC组织及癌旁正常组织中的AGAP2-AS1表达水平,并进行比较。分析AGAP2-AS1表达与NSCLC患者临床病理特征关系,分析AGAP2-AS1表达水平与NSCLC患者预后的关系。结果 NSCLC组织中AGAP2-AS1表达水平高于癌旁正常组织,差异有统计学意义(P<0.05)。肿瘤直径≥3 cm、TNM分期Ⅲ期+Ⅳ期、分化程度低分化、淋巴结转移患者的AGAP2-AS1表达水平高于肿瘤直径<3 cm、Ⅰ期+Ⅱ期、中分化+高分化、无淋巴结转移患者,差异有统计学意义(P<0.05);不同年龄及性别患者的AGAP2-AS1表达水平比较,差异无统计学意义(P>0.05)。随访2年,95例患者死亡40例,生存55例;死亡组患者的AGAP2-AS1表达水平高于生存组,差异有统计学意义(P<0.05)。结论 NSCLC组织中AGAP2-AS1呈高表...     

血清长链非编码RNA MALAT1和AFAP1-AS1与鼻咽癌临床病理特征和预后的关系

目的 探讨血清长链非编码RNA(lncRNA)MALAT1和AFAP1-AS1与鼻咽癌临床病理特征和预后的关系。方法 2013年4月—2015年6月在我院经病理证实的鼻咽癌患者136例为鼻咽癌组,同期选择我院门诊健康体检者54例为对照组,实时荧光逆转录法分析MALAT1和AFAP1-AS1的表达;采用χ²检验分析MALAT1和AFAP1-AS1表达与临床病理特征的关系;Log-rank检验分析血清MALAT1和AFAP1-AS1不同表达水平患者的预后差异。结果 与对照组比较,鼻咽癌组MALAT1和AFAP1-AS1表达水平明显升高,差异有统计学意义(P＜0.001);MALAT1和AFAP1-AS1表达与年龄无关(P＞0.05);肿瘤最大径≥5 cm、病理学分期越高、TNM分期越高、浸润深度越深、有淋巴血管间隙浸润、有淋巴结转移、有复发的鼻咽癌患者MALAT1和AFAP1-AS1高表达率升高(P＜0.05);MALAT1和AFAP1-AS1低表达组2年生存率及生存期均明显高于MALAT1和AFAP1-AS1高表达组(P＜0.001);多因素Cox逐步回归分析,结果发现MALAT1低表达(HR=0.52,95% CI:0.37~0.81)和AFAP1-AS1低表达(HR=0.56,95% CI:0.51~0.83)为鼻咽癌患者预后的独立保护因素(P＜0.001)。结论 鼻咽癌患者血清lncRNA MALAT1、AFAP1-AS1水平升高,且与鼻咽癌恶性进展有关;鼻咽癌患者血清MALAT1、AFAP1-AS1低表达患者预后良好;MALAT1、AFAP1-AS1可能作为诊断鼻咽癌的新型标志物。     

长链非编码RNA DLX6-AS1在结肠癌组织与细胞中的表达及其临床意义

目的:检测长链非编码RNA DLX6-AS1（distal-less homeobox 6 antisense 1）在结肠癌组织和细胞中的表达，探讨DLX6-AS1与结肠癌临床病理特征及预后间的关系。方法:利用RT-PCR检测结肠癌组织、细胞及配对癌旁组织、黏膜上皮细胞中DLX6-AS1的表达；利用单因素方差分析DLX6-AS1与结肠癌患者临床病理特征之间的关系；利用生存曲线分析DLX6-AS1与结肠癌患者术后5年生存率的关系；利用Cox风险比例模型分析DLX6-AS1与结肠癌患者预后的关系。结果:DLX6-AS1在结肠癌组织、细胞中表达水平高于癌旁组织和结肠上皮细胞；DLX6-AS1的表达与结肠癌TNM分期相关（P<0.05）；DLX6-AS1高表达的结肠癌患者术后5年生存率低于低表达的患者，DLX6-AS1表达是结肠癌患者独立的预后因素。结论:DLX6-AS1在结肠癌中表达升高，并与结肠癌患者生存及预后密切相关。     

LncRNA NR2F1-AS1在结肠癌组织中的表达及其与预后的相关性

目的:探讨长链非编码RNA(LncRNA)核受体亚家族2F组成员1-反义RNA 1(NR2F1-AS1)在结肠癌患者中的表达水平及其与预后的相关性。方法:选取本院2015年07月至2017年02月诊治的93例结肠癌患者的癌组织及对应癌旁正常组织进行研究。采用实时荧光定量PCR（qRT-PCR）法检测结肠癌组织及对应癌旁正常组织LncRNA NR2F1-AS1表达水平;分析癌组织LncRNA NR2F1-AS1表达水平与结肠癌患者临床病理特征的相关性;采用Kaplan-Meier曲线法分析结肠癌患者癌组织中LncRNA NR2F1-AS1表达水平与结肠癌患者预后的相关性;采用COX回归分析结肠癌预后的影响因素。结果:结肠癌组织LncRNA NR2F1-AS1表达水平明显低于癌旁正常组织（P＜0.05）;结肠癌患者癌组织LncRNA NR2F1-AS1表达水平与结肠癌患者TNM分期、淋巴结转移、浸润深度、分化程度相关（P＜0.05）,而与结肠癌患者性别、年龄、肿瘤大小、位置无关（P＞0.05）;结肠癌患者LncRNA NR2F1-AS1低表达组术后36个月总生存率(OS)、无病生存率(DFS)明显低于LncRNA NR2F1-AS1高表达组OS、DFS（P＜0.05）;COX回归分析显示,TNM分期、淋巴结转移是影响结肠癌患者预后的独立危险因素（P＜0.05）,LncRNA NR2F1-AS1是影响结肠癌患者预后的独立保护因素（P＜0.05）。结论:LncRNA NR2F1-AS1在结肠癌患者癌组织中表达水平明显降低,且低水平LncRNA NR2F1-AS1与结肠癌患者不良预后密切相关,有利于判定结肠癌患者预后情况。     

长链非编码RNA PCBP1-AS1在乳腺癌组织中的表达及临床意义

目的:研究多聚胞嘧啶结合蛋白1反义长链非编码RNA（lncRNA PCBP1-AS1）在乳腺癌组织中的表达及临床意义。方法:选取2013年5月至2016年4月在本院进行手术治疗的105例乳腺癌患者作为研究对象,将切除的癌组织作为试验组,同时取同一患者的癌旁（距肿瘤边缘＞2 cm）组织作为对照组。用实时荧光定量PCR（qRT-PCR）检测lncRNA PCBP1-AS1表达情况;分析lncRNA PCBP1-AS1与乳腺癌病理参数关系;分析lncRNA PCBP1-AS1表达情况对乳腺癌患者生存情况的影响;Cox回归分析影响乳腺癌的预后因素。结果:试验组lncRNA PCBP1-AS1表达明显低于对照组（P<0.05）;乳腺癌患者癌组织中lncRNA PCBP1-AS1表达水平与患者年龄、肿瘤直径、绝经情况和病理类型相关性不明显（P>0.05）,与淋巴结转移和TNM分期有关（P<0.05）;绘制乳腺癌患者术后36个月生存曲线,lncRNA PCBP1-AS1高表达患者的总生存率明显高于低表达患者（P<0.05）;对lncRNA PCBP1-AS1表达、淋巴结转移和TNM分期进行Cox回归分析,显示lncRNA PCBP1-AS1表达是影响乳腺癌患者预后的独立保护因素,TNM分期是影响乳腺癌患者预后的独立危险因素。结论:乳腺癌患者癌组织中lncRNA PCBP1-AS1呈低表达,其表达水平与淋巴结转移和TNM分期有关,lncRNA PCBP1-AS1表达是乳腺癌预后独立保护因素,可作为乳腺癌预后判断指标之一,有望成为乳腺癌治疗的潜在靶点。     

胃癌组织中lncRNA FOXF1-AS1的表达及其与临床病理特征及预后的关系

目的:探究胃癌组织中长链非编码叉头蛋白F1-反义RNA1（lncRNA FOXF1-AS1）表达水平及其与临床病理特征及预后的关系。方法:以2014年2月至2015年7月于本院就诊胃癌患者87例为研究对象。术中取患者胃癌组织及癌旁（＞5 cm）组织,荧光定量PCR检测胃癌组织及癌旁组织中lncRNA FOXF1-AS1表达水平,收集分析患者临床资料及临床病理特征,Kaplan-Meier分析胃癌患者3年生存情况,COX回归分析影响胃癌不良预后发生的危险因素。结果:胃癌组织中lncRNA FOXF1-AS1表达水平显著低于癌旁组织（P＜0.05）;根据lncRNA FOXF1-AS1表达平均值将患者分为高表达组和低表达组,lncRNA FOXF1-AS1表达水平与胃癌患者浸润深度、淋巴结转移、TNM分期有关（P＜0.05）,与患者年龄、病理类型、肿瘤直径大小无关（P＞0.05）;Kaplan-Meier分析结果显示lncRNA FOXF1-AS1高表达患者3年无进展生存率和总生存率显著高于lncRNA FOXF1-AS1低表达组（P＜0.05）;COX多因素分析结果显示肿瘤淋巴转移、lncRNA FOXF1-AS1表达水平是影响胃癌患者预后的独立危险因素（P＜0.05）。结论:lncRNA FOXF1-AS1在胃癌组织中表达下调,与胃癌患者浸润深度、淋巴结转移及生存情况有关,是影响患者预后的独立危险因素,可作为患者预后判断的参考指标。     

Skp1蛋白在非小细胞肺癌组织和外周血中的表达水平及其临床意义

目的：检测S期激酶相关蛋白1（Skp1）在非小细胞肺癌（NSCLC）组织和外周血中的表达水平并探讨其临床意义。方法：采用Western blot检测34例NSCLC组织及相应癌旁组织中Skp1蛋白的表达水平。采用组织芯片和免疫组织化学染色检测Skp1在86例NSCLC组织及相应癌旁组织中的表达情况,并分析Skp1蛋白的表达与NSCLC临床病理指标及患者预后的关系。采用酶联免疫吸附试验（ELISA）检测39例NSCLC患者及27例健康人血浆中的Skp1蛋白水平。结果：Western blot和免疫组化法分析结果显示Skp1蛋白在NSCLC组织中的表达水平均显著高于相应癌旁组织（P < 0.001）。ELISA法分析结果显示NSCLC病人血浆中的Skp1蛋白表达水平显著高于健康人群（P=0.003）。Kaplan-Meier单因素生存分析显示Skp1蛋白在NSCLC组织中的高表达与中晚期（Ⅱ+Ⅲ） NSCLC患者的不良预后显著相关（P=0.001）,多因素Cox回归分析显示Skp1蛋白能够作为影响中晚期（Ⅱ+Ⅲ） NSCLC患者预后的独立危险因素。Skp1蛋白表达水平与病理类型、临床分期、分化程度、淋巴结转移等因素无显著相关关系（P > 0.05）。结论：Skp1蛋白在NSCLC患者中高表达,并且Skp1蛋白在NSCLC组织中的高表达与中晚期（Ⅱ+Ⅲ） NSCLC患者的不良预后显著相关,可作为中晚期NSCLC患者预后的独立危险因素。     

非编码RNA肌动蛋白纤维相关蛋白1-反义RNA对子宫内膜癌的诊断价值

目的 探究长链非编码RNA(LncRNA)肌动蛋白纤维相关蛋白1-反义RNA(AFAP1-AS)在子宫内膜癌(EC)中的表达意义,并分析其对EC的诊断价值。方法 选取郑州人民医院2017年1月至2022年1月收治的45例确诊的EC患者为研究对象,作为观察组,选择同期确诊为子宫肌瘤并接受子宫切除手术的50例患者为对照组。收集观察组癌组织和对照组正常子宫内膜组织,采用实时荧光定量PCR(qRT-PCR)法检测2组患者组织样本中LncRNAAFAP1-AS表达水平,分析其在不同临床病理特征癌组织中的表达情况,并采用受试者工作特征(ROC)曲线分析LncRNA AFAP1-AS对EC的诊断价值。结果 EC患者癌组织中LncRNA AFAP1-AS相对表达量明显高于对照组,差异有统计学意义(t=37.106,P<0.001)。FIGOⅢ～Ⅳ期、病理Ⅲ级、肌层深浸润均为EC患者LncRNA AFAP1-AS高表达的危险因素(OR=0.172,P=0.044;OR=0.151,P=0.014;OR=0.214,P=0.040)。ROC曲线显示,LncRNA AFAP1-AS对EC具有较高诊断价...     

溶血卵磷脂胆碱酰基转移酶1与非小细胞肺癌患者临床特征及预后的关系

目的 分析溶血卵磷脂胆碱酰基转移酶1(LPCAT1)与非小细胞肺癌(NSCLC)患者临床特征及预后的关系.方法 收集95例NSCLC患者癌旁组织及肿瘤组织,采用实时定量逆转录聚合酶链反应(qRT-PCR)法对其癌旁组织及肿瘤组织中的LPCAT1 mRNA相对表达量进行比较,分析LPCAT1 mRNA相对表达量与NSCLC患者临床特征及预后的关系.结果 NSCLC患者癌旁组织LPCAT1 mRNA相对表达量为(0.069±0.017),明显低于肿瘤组织的(0.621±0.124),差异有统计学意义(P﹤0.01).TNM分期为Ⅲ期、有淋巴结转移的NSCLC患者肿瘤组织中LPCAT1 mRNA相对表达量均明显高于TNM分期为Ⅰ～Ⅱ期、无淋巴结转移者(P﹤0.01);不同年龄、性别、病理类型、肿瘤直径、分化程度及是否吸烟NSCLC患者的肿瘤组织中LPCAT1 mRNA相对表达量比较,差异均无统计学意义(P﹥0.05).LPCAT1 mRNA相对表达量高水平组患者总生存率为37.50％,低于低水平组的68.09％,差异有统计学意义(P﹤0.05).结论 NSCLC患者肿瘤组织中LPCAT1 mRNA相对表达量高于癌旁组织,且NSCLC患者临床特征及预后与LPCAT1 mRNA相对表达量有关.     

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.