Dissertations / Theses on the topic 'Worker polymorphism'

碩士<br>高雄醫學大學<br>公共衛生學系公共衛生學碩士班<br>106<br>Introduction and aims: Lead is widely used in occupational environments and can enter the body through many ways, accumulate in tissues, affecting nerves, hematopoiesis, reproductive system etc. The nephrotoxicity caused by lead exposure will damage the proximal tubule and hurt the renal function. Some studies have shown that different genotypes have different susceptibility to lead. The aim of this study was to investigate the relationship between MT1A nucleotide polymorphism and renal function in chronic lead exposure workers. Methods: The chronic lead-exposed subjects were selected from the lead battery manufacturing factorys. The blood and urine samples were obtained during the annual worker’s health surveillance. Blood lead levels were evaluated by ICP-MS and put into the formula as indics of different blood lead exposures. The MT1A nucleotide gene polymorphisms were analyzed by RT-PCR with Sanger’s methods. Results: Lead exposure indics and renal function indics were statistically significant. The relationship between lead exposure indics and MT1A SNPs and renal function indics was statistically significant, and the interaction between lead exposure indics and genotype were statistically significant. Conclusion: This study found that the renal function of the chronic lead exposed workers were affected by the MT1A SNPs. It was also found that the creatinine adjusted urine NAG of the chronic lead exposed workers were increased with lead exposure. And there was shown an interaction between lead exposure and genotype. The eGFR of the chronic lead exposure workers were also affected by the interaction between lead exposure and genotype.

碩士<br>高雄醫學大學<br>職業安全衛生研究所碩士班<br>94<br>Objective：To investigate the variance among different Metallothionein 1A (MT1A) genotypes and the effects on biomarkers in lead workers. Materials and Methods：The subjects are lead workers from two plants in Taiwan. We obtained their annual health examination data and their renal function markers. The questionnaire information which contains demographic data, smoking, alcohol, and food consumptions was also collected. We extracted DNA from blood, and amplified DNA with real-time PCR, then verified the sequence of these DNA products. We obtained the MT1A gene A/C (Asn/Thr) and A/G (Arg/Lys) genotypes on exons 2 and 3. The descriptive analysis, one-way ANOVA, and multiple linear regression was performed. Results：There was significant difference on adjusted urine uric acid concentration among three genotypes on exon 2, while there was significant difference on adjusted NAG concentration among three genotypes on exon 3. After controlling potential confounding factors, blood uric acid concentration increased and urine creatinine adjusted γ-GT contentration decreased with blood lead level. The adjusted urine uric acid decreased with time weighted index of cumulated lead level. After controlling potential confounder, the adjusted urine uric acid concentration in exon 2 AC genotype workers is lower than those workers with CC genotype while exon 3 AG genotype workers was lower than AA genotype workers. The adjusted NAG concentration in exon 3 AG genotype workers was lower than those of workers with AA genotype after controlling confounders. Conclusion：There were significant difference on the creatinine adjusted urine uric acid and NAG concentrations among the two MT1A SNPs with controlling the other potential confounders.

碩士<br>高雄醫學大學<br>生物醫學檢驗學研究所碩士班<br>96<br>In Taiwan, Chinese restaurant cooks work more than 6 hours per day in the kitchen. They suffer serious health problems by being exposed to indoor air pollution arising from the cooking oil fumes (COF) in their daily lives. Several studies have established the presence of oxidative stress in cooking oil fumes, but the determinants of oxidative stress in cooking workers population and especially the contribution of the genotype of the xenobiotics- metabolizing enzymes (XME) to the observed oxidative stress are incompletely understood study. The aim of this study is to discuss the association between polymorphisms of metabolic genes with malondialdehyde (MDA) levels induced by COF. In our study, we investigated 192 Chinese restaurant workers in Northern Taiwan. In addition to a questionnaire survey, serum and urinary levels of MDA were measured as oxidative biomarkers. Cytochrome P450 (CYP) 1A1, CYP1A2, CYP1B1, CYP2E1, Glutathione S- transferase (GST) M1, GSTT1 and GSTP1 polymorphisms were evaluated to determine the effect of genetic modification on serum and urinary MDA. Levels of MDA were statistically significant difference with CYP1A1 and CYP2E1 genotype in service and culinary subjects, respectively (p<0.05). Both serum and urinary levels of MDA among total study participants found statistically significant difference (p < 0.05) between the genotypes of GSTT1 and GSTM1, respectively. Especially, both the average serum and urinary levels of MDA of the subjects with GSTT1 and GSTM1 present genotype was higher than null genotype in total participants (1.5 ± 0.6 μmol/L versus 1.3 ± 0.5 μmol/L, p=0.02; 2.4 ± 1.3 μmol/g creatinine versus 2.0 ± 1.0 μmol/g creatinine, p=0.015, respectively). In conclusion, we contribute the systemic detoxification reaction which involved metabolizing genes polymorphisms and oxidative stress in workers exposed to COF. Additionally, our results provided here regarding the influence of the GSTT1 and GSTM1 detoxifying genotype on MDA levels determination in Chinese restaurant workers, is valuable for future environmental- occupational studies using this biomarker, suggesting that GSTT1 and GSTM1 should be determined in future studies involving MDA determinate where COF exposed is a factor.

碩士<br>國防醫學院<br>公共衛生學研究所<br>94<br>(4, 4 methylene-bis(2- chloroaniliene); MBOCA) is used as curing agent in isocyanate polymer and epoxy resin. The chemical constitution of MBOCA is similar to benzidine (A1 carcinogen ). Due to limited evidence of carcinogenicity to human, MBOCA is considered to be a suspected carcinogen (A2) by American Conference of Governmental Industrial Hygienist (ACGIH), and is considered to be probably carcinogenic to human by International Agency of Research on Cancer (IARC). Recent studies have reported that workers exposed to MBOCA may lead to bladder cancer in Taiwan. The objective of this study is to investigate the association between biomarker of oxidative stress (8-OHdG) and MBOCA exposure and to study the modification effect (interaction) of genetic polymorphism of metabolizing enzyme N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2). The study population was recruited from four MBOCA-manufacturing factories in Taiwan. Based on the job titles and workplace, the study subjects was classified as exposed groups (n =57)and comparison groups (n =106). The personal characteristics and personal habits were collected by questionnaire. Urine was collected to measure MBOCA and its metabolite, N-acetyl MBOCA. Plasma was collected to measure 8-Hydroxydeoxyguanosine (8-OHdG) as oxidative stress index. MBOCA and N-acetyl-MBOCA of urine and plasma of 8-OHdG were measured by LC/MS/MS. DNA was extracted to measure NAT1 and NAT2 polymorphism. Genetic polymorphism of NAT1 and NAT2 were measured by polymerase chain reaction-based restriction fr agment length polymorphism (PCR-RFLP) methods. Urinary internal doses of MBOCA exposure were compared between this year (2005)and two years ago (2003)and between pre-manufacturing and post-manufacturing. The results showed that the concentration of MBOCA and N-acetyl-MBOCA in urine was significantly lower in 2005 than in 2003 (P =0.004 and 0.003). The period of producing MBOCA takes approximately 7 to 10 days. The urinary concentration of MBOCA and N-acetyl-MBOCA in post-manufacturing period was higher than pr e-manufacturing period, but the difference was not significant (P =0.164, P =0.253). However, the results revealed a cumulative effect of MBOCA exposure. The main metabolism for MBOCA is N-acetylation and results in N-acetyl-MBOCA metabolite. The ratio of N-acetyl-MBOCA to MBOCA is around 10% in exposed workers. Due to the ability of N-acetylation, We found that rapid acetylator in NAT2 metabolizes more MBOCA into Acetyl (CoA) and lead to higher N-acetyl-MBOCA and N-acetyl-MBOCA/MBOCA ratio. On the other hand, slow acetylators in NAT2 had higher concentration of MBOCA, lower concentration of N-acetyl-MBOCA and N-acetyl-MBOCA/MBOCA ratio. These findings are compatible with that slow acetylators in NAT2 have greater risk in cancer than in rapid acetylators. No significant difference of mean 8-OHdG was found between MBOCA-exposed and comparison groups (p value =0.297). Oxidative stress index of 8-OHdG was further studied of modification effect by genetic polymorphism. Genotype AA in NAT1 1058 or 1069 alleles had a higher risk of having high 8-OHdG (>6.17 pg/mL) with comparison to genotype TT or CC (OR =1.33)in the exposed group. While in comparison group, Genotype AA in NAT1 1058 or 1069 alleles had a lower risk compared to genotype TT or CC (OR =0.30). But both associations were not statistically significant. The 8-OHdG concentration was significantly associated with NAT2 phenotypes. In the exposed group, slow acetylator has the highest 8-OHdG level (7.66 pg/mL), followed by intermediate acetylator (6.06 pg/mL), and rapid acetylator has the lowest 8-OHdG level (5.70 pg/mL). Both the p-value for group difference and p-value for trend test are statistically significant (P =0.016, P for trend =0.031). Even after adjusted some confounders, the difference was still significant between slow acetylators and intermediate plus rapid acetylators. But there was no trend found in the comparison group and in total subjects. After adjusted for some confounders in logistic regression model, slow acetylators in total population was 10.35 times (95% C.I. =1.04-103.15)higher risk to have high 8-OHdG than rapid and intermediate acetylators. NAT2 slow acetylators in the exposed group only had 15.0 times higher risk. These results showed MBOCA exposure and NAT2 polymorphism had interaction on 8-OHdG concentration. The findings suggest a gene - environment interaction. This study showed that polymorphism of N-acetyltransferase plays an important role in MBOCA-exposed workers. In order to protect workers from health hazards, improvement of the work environment and wearing of personal protective equipments are required. If the above-mentioned methods are not appropriate, selection of rapid acetylators by screening may be applied in occupational health to reduce the risk of cancer.

碩士<br>國立臺灣大學<br>職業醫學與工業衛生研究所<br>92<br>Vinyl chloride monomer (VCM) is a known human carcinogen. Previous studies also showed that vinyl chloride exposure might lead to abnormal liver function and chronic liver diseases. However, the dose-response between vinyl chloride and chronic liver diseases remains unclear. Thus, we reconstructed the VCM cumulative dose according to job exposure matrix model, environmental assessment and detail working history of PVC workers. The aim of this study is to evaluate the dose-response relationship between chronic liver diseases and VCM exposure. Further, VCM is metabolized by CYP2E1 to the electrophilic metabolites. These metabolites may affect the function of cell. Thus, we also investigate the effects of genetic polymorphism of metabolic genes and DNA repair gene on VCM-induced chronic liver diseases. A total of 327 male workers with VCM exposure from five polyvinyl chloride plants were included in this study. Their specimens and epidemiology information had been collected during 1995 to 1999. The chronic liver diseases were diagnosed by ultrasonography. The result revealed that the OR of chronic liver diseases increased with increasing cumulative dose. The lowest exposure group (less than 40 ppm-years) was used as a reference group. The adjusted odds ratio for the presence of the chronic liver diseases increased from 3.5 (95%CI=0.4-32.1) for those with dose of 40-1000 ppm-years to 4.1 (95%CI=0.4-43.9) for those dose of 1000-10000 ppm-years and 5.6 (95%CI=0.5-68.4) for those with dose more than 10000 ppm-years. HBs-Ag positive and/or anti-HCV positive were independent factors for chronic liver diseases (OR=6.2, 95%CI=2.3-16.9). We did not observe an interaction between VCM exposure and chronic liver diseases. Subjects experiencing the cumulative dose more than 1000 ppm-years and with variants of XRCC1 Gln-Gln demonstrated greater risk of chronic liver diseases among those having different combinations of VCM cumulative dose and XRCC1 genotypes (OR=10.1, 95%CI=1.2-85.1 ). Similarly, individuals experiencing the cumulative dose more than 1000 ppm-years and with CYP2E1 c2c2 genotype had higher risk of chronic livers diseases among those having different combinations of VCM cumulative dose and CYP2E1 genotypes (OR=7.8, 95%CI=1.3-46.1). Further, we found the polymorphism of DNA repair gene XRCC1 and HBs-Ag and/or anti-HCV infection for chronic liver diseases had greater risk among those having different combinations of HBV and/or HCV infection and XRCC1 genotypes (OR=28.0, 95%CI=3.4-231.8). Our results revealed that VCM exposed workers had increased risk with VCM exposure and the workers with susceptible XRCC1 and CYP2E1 genes had higher risk for chronic liver diseases. Lastly, the workers with susceptible XRCC1 gene and HBs-Ag and/or anti-HCV infection had greater risk for chronic liver diseases. Thus, the VCM levels at worksite need to be considered, when workers with susceptible genotype and HBV or HCV infection are placed in this environment.

碩士<br>國立成功大學<br>環境醫學研究所<br>96<br>Benzene was common by-product in coal chemistry process, and it was one of the major occupational benzene exposure sources. Reports reveal that employees who are exposed to high benzene concentrations could have elevated risk of leukemia, and the complete blood count (CBC) decreases even at low exposure. Moreover, the latency period extended about 4 months to 10 years, but few study have researched the long term hematological parameters among low benzene-exposed healthy workers. After inhalatary and dermal exposure, the remainder of benzene is metabolized in the body and excreted through urine. S-phenylmercapturic acid（S-PMA）is the specific metabolite of benzene, and hydroquinone（HQ）is a benzene-derived toxicity found by in vitro study. These metabolites modulated by enzymes, Cytochrome P450 2E1（CYP2E1）, Glutathione S-transferase（GST）and NAD(P)H:Quinone Oxidoreductase （NQO1）with genetic polymorphisms. Thus, the genetic polymorphism of aforementioned enzymes could affect the metabolic pathway of exposed benzene and human susceptibility of benzene-derived toxicity. The objectives of this study were （1） to study the effects of various genetic polymorphisms on levels of HQ and S-PMA;（2） to investigate the dose-response between the levels of HQ and alteration of hemotological parameters; and （3） to investigate the CBC outcomes over years in relation to individual genotype of CYP2E1, NQO1, GST. Eighty-four workers were recruited based on different benzene-exposed levels in a coal chemistry plant from southern Taiwan. We have analyzed the airborne benzene, the hematological parameters, single nucleotide polymorphisms (SNPs) in CYP2E1- c.-1259C>T, CYP2E1- c.7668T>A, NQO1- c.609C>T, GSTM1, GSTT1, and long term physical examination records since 1990 to 2006 for each participant. Genetic polymorphisms of CYP2E1 and NQO1 were analyzed by restriction fragment length polymorphism（RFLP）, and GSTs were analyzed by polymerase chain reaction（PCR）. The levels of S-PMA and HQ in urine samples were determined by high performance liquid chromatography- electrospray ionization tandem mass spectrometry（HPLC-ESI-MS/MS）and Gas Chromatography-Mass Spectrophotometer（GC-MS）respectively. We found:（1）personal airborne benzene concentration showed log normal distribution. Medium levels of air-Bz and urinary S-PMA were 29.44 ppb and 0.055 μg/g creatinine, respectively, and those levels far below the current permissible exposure limit and biological exposure index; （2）The level of HQ in workers was increased significantly in the end-shift, and it indicated that the benzene exposure in work place would cause personal urinary HQ rising. However, significant correlation was not found between air benzene and HQ（r=0.18，p=0.116）due to the low benzene concentration; （3）The genotype of CYP2E1- c.-1259C>T, CYP2E1- c.7668T>A might not effect the level of HQ and S-PMA in low benzene-exposed workers; （4）The level of S-PMA might not be effect by the genetic polymorphism of GSTT1, but GSTM1. Our data revealed subjects with GSTM1 null type have more S-PMA in urine than GSTM1 non null type; （5）No significant relationship was found between urinary HQ level and genotype of GSTs in benzene-exposed workers.（6）Urinary HQ level were found significantly higher in individuals with NQO1 c.609 T/T compared to those with NQO1 c.609 C/T（or C/C）; （7）No significant odds ratios in genotypes of CYP2E1, NQO1, GST between all hematological parameters in 2006 physical examination were found.（8）Individuals with NQO1 c.609 T/T×CYP2E1 c.-1259 C/T（or T/T）, NQO1 c.609 T/T×CYP2E1 c.7668 T/A（or A/A） tended to be more susceptible to have abnormal red blood cell counts（RBC）, mean corpuscular volume（MCV）, mean corpuscular hemoglobin（MCH） than NQO1 c.609 C/T（or C/C）×CYP2E1 c.-1259 C/C, NQO1 c.609 C/T（or C/C）×CYP2E1 c.7668 T/T （odds ratio=6.56∼7.61）; （9） We also observed a 10.5-fold increased risk among workers with GSTs null type compared to those with GSTs non null type; （10） Long term benzene-exposed workers who carry genotypes of CYP2E1 c.-1259 T/C（or T/T） have significant higher risk of abnormal lymphocytes than those carry CYP2E1 c.-1259 wild type;（11）Subjects with NQO1 c.609 T/T× GSTT1 null genotype and smoked was found decreased long term average WBC and RBC respectively.

碩士<br>中國醫藥學院<br>環境醫學研究所<br>89<br>Abstract The issue of environmental pollution in incinerating the medical waste has been concerned by the general public. In this study, DPC in peripheral blood lymphocytes were measured as an endpoint of cytogenetic damage. However, this kind of study is frequently complicated by variants confounding factors, both endogens (sex, age) and exogenous(life style, smoking , alcohol abuse ,diet habits etc.)In this study ,31 medical waste incinerator workers and 31 normal subjects as a matched control were enrolled. The purpose of the present study is to investigate whether genetic polymorphisms in CYP1A1 and GSTM1 could explain some of the variation in DPC. DPC levels were significantly higher in the medical waste incinerator workers compare to the control group (1.5 versus 0.9 DPC% , p<0.01).We measured the association between GSTM1 null genotype, which results in loss of enzyme activity, and DPC levels, hypothesizing that subjects with this genotype would have higher levels of DPC. However, there was no association with the GSTM1 polymorphism and DPC levels both in workers (for GSTM1 non null , DPC%=1.5; for GSTM1 null, DPC%=1.5; p=0.4)and controls (for GSTM1 non null , DPC%=0.9; for GSTM1 null, DPC%=1.1; p=0.27).Similarly, there was no association with the CYP1A1 MspⅠpolymorphism and DPC levels in workers(for CYP1A1 MspⅠwt/wt+wt/vt , DPC%=1.6; for CYP1A1 MspⅠvt/vt , DPC%=1.5; p=0.3) and controls (for CYP1A1 MspⅠwt/wt+wt/vt , DPC%=0.9; for CYP1A1 MspⅠvt/vt , DPC%=1.0; p=0.17). Higher DPC levels in medical waste incinerator workers suggest that this group are at increased risk for exposing to ambient air pollution contaminated with PAHs . Key word: medical waste incinerator, DPC (DNA protein crosslinks), CYP1A1, GSTM1.

碩士<br>高雄醫學大學<br>公共衛生學系職業安全衛生碩士班<br>103<br>Background Lead toxicity is an important public health issue. It causes multiple organs damage, and nephrotoxicity is included. Metallothionein (MT) is a cysteine-rich, low molecular weight protein with function of heavy metal detoxification. Among the functional MT gene, MT1A and MT2A are existed in all organs in human. However, study about how the MT1A and MT2A single nucleotide polymorphisms (SNPs) influence the lead nephropathy is relatively scarce. Objectives Our aim is to investigate the association of blood lead levels and renal biomarkers in chronic occupational lead-exposed workers, and to study whether the association was affected by the combinations of MT1A and MT2A SNPs. Materials and Methods Blood samples were collected from 485 participants during their annual health examination after informed consent letters were obtained. The blood lead level, serum creatinine, serum uric acid, urinary creatinine, urinary uric acid, and urinary N-acetyl-beta-d-glucosaminidase (NAG) were measured and analyzed. DNA was extracted and used for real-time PCR of type 2 MT1A SNPs (rs11640851 and rs8052394) and 2 MT2A SNPs (rs10636 and rs28366003). Furthermore, we classified our participants into wild type genetic carriers and variant type ones. In MT1A rs11640851, we regarded the CC carrier as wild type, while CA and AA carriers as variant types. The same principle of classification was also applied in MT1A rs8052394, MT2A rs10636 and rs28366003. Then, we combined the wide type and variant type of these 4 SNPs into 16 different groups. Data was treated for descriptive analysis, one-way ANOVA, and multiple linear regressions by SPSS. Result Urine uric acid had significantly negative association with time-weighted index of cumulative blood lead (TWICL) after adjusting other potential confounders except 16 groups of MT1A2A SNPs combination (β -0.20, p value 0.0018). Moreover, the association was modified by 16 groups of SNPs combination. For urine uric acid, group 6th, 7th, 9th and group 12th were more susceptible to lead toxicity (β -13.52, p value 0.0008; β -9.20, p value 0.019; β -9.70, p value 0.041; β -10.97, p value 0.0047), while group 5th was less susceptible to lead toxicity (β 12.47, p value 0.0047). Conclusion In conclusion, urinary uric acid and urinary NAG might be considered as proper indicators of lead nephrotoxicity. Moreover, MT1A2A combination 16 groups is a modifier of TWICL on urinary uric acid. Group 6th, 7th, 9th, and 12th are more susceptible to lead toxicity, while group 5th is less susceptible to lead toxicity.

碩士<br>高雄醫學大學<br>醫學研究所<br>101<br>Aim: The goal of this study is to investigate the lead induced health effects whether modified byMetallothionein-2A (MT-2A) genetic polymorphisms. Materials and Methods: The study subjects were lead workers and adults participating in the health examination. The data of demographic and health examination were collected. Genomic DNA was extracted and stored until genotyping. Single nucleotide polymorphism (SNP) rs10636 and rs28366003 were genotyped using Real-time multiplex polymerase chain reaction (PCR). We performed descriptive analyses, Pearson correlation, analysis of variance (ANOVA), and linear regression models to examine the association of MT-2A polymorphisms and blood lead levels on results of health examination. Result: The data grouped by rs10636 genotypes with multiple linear regression analysis showed that people carrying rs10636 GC & CC genotypes may reduce high-density lipoprotein (HDL) 0.149 mg/dL if their blood lead values increase 1 μg/dL, but the low-density lipoprotein (LDL) was not significant; while people with rs10636 GG genotype will increase LDL significantly 0.467 mg/dL with blood lead per unit increasing, but no significant effect on HDL. Grouped according to rs28366003 genotypes, use of multiple linear regression analysis, people with rs28366003 AA genotype showed that each additional 1 μg/dL blood lead levels may reduce HDL 0.121 mg/dL significantly, and their LDL significantly increased 0.369 mg/dL; people with rs28366003 AG genotype increased 1 μg/dL blood lead level may reduce HDL 0.224 mg/dL significantly, but no significant effect on LDL. Conclusions: The association of blood lead levels with HDL and LDL concentrations may be modified by MT2A genetic variations.

碩士<br>高雄醫學大學<br>職業安全衛生研究所<br>91<br>We followed up a group of lead workers (n=530) from 1997 to 2002. The health examination data consisted of: blood lead levels, serum creatinine and uric acid levels, blood pressure levels. A questionnaire was used to collect potential confounder in the health examination. DNA was isolated from the whole blood of each worker. The ACE I/D and a-adducin G460W polymorphism are investigated by polymerase chain reaction and restriction fragment length polymorphism amplification of genomic DNA to define the The ACE I/D and a-adducin G460W genotypes. The main purpose of this study is to investigate the association among the different ACE I/D and a-adducin G460W genotypes to the renal functions and blood pressure in long-term lead exposed workers. The interaction of lead and gene polymorphism on renal functions and blood pressure was also evaluated in this study. In 2002, totally 530 lead workers were recruited. Of them, 312（59%）were men. The average age was 43（SD=7.9）years, and , mean working duration was 13（SD=7.8）years. Among them, blood pressure（mean systolic pressure: 123 mmHg; mean diastolic pressure: 77 mmHg）, renal function tests（mean creatinine: 0.95 mg/dL）, uric acid（mean: 6.37 mg/dL）were found. Their average blood lead level was 22 mg/dL. ACE I/D genotypes distributed as II: 192（42%） people, DI: 116（26%） people, II: 144（32%） people. a-adducin G460W genotypes distributed as GG: 124（28%）people, GW: 235（53%）people, WW: 88（19%）people. Regarding renal functions using general linear mixed models analyses with adjustment of age, gender, body mass index, smoking habit, we found that the interaction of blood lead levels and ACE I/D types associated to serum creatinine levels and creatinine clearance rate. The analyses of uric acid levels with general linear mixed models found that blood lead levels significantly related with serum uric acid levels after adjusting the confounders. For blood pressures by general linear mixed models analyses with adjustment of age, gender, body mass index, smoking habit, there was no relation between blood pressure levels and ACE I/D, a-adducin G460W genotypes, blood lead levels. In conclusion, the toxicity of lead to renal function may be affected by differential ACE I/D genotypes. Further studies and further assessment are clearly needed.

碩士<br>高雄醫學大學<br>公共衛生學研究所<br>98<br>Past researches almost explored the relationship between a single gene with a single disease. Our study aims to investigate into the interaction of multi-gene with a single disease by using Genetic Algorithms.Our research focuses on the 506 employees of a lead battery factory in Taiwan, in 2009. We collected the data of their bone density, blood lead level and 6 SNPs (ACE,alpha-adducin, Bsm, Tag, Apa, ALAD). However, not each of them has complete 6 SNPs, thus we use AMELIA II to estimate the missing SNP. We found the results by using Genetic Algorithms and logistic regression analysis that the genotype in an individual which are Bsm bb type and ALAD 1-1 type plays an important role in protecting bone density among 245 male employees and 261 female employees. In other words, the lead employees who has the genotype could protect against low bone density in comparison to other genotypes. Besides, no significant association between blood lead level and bone density can be found owing to the similarity in age among this population (the average age is 45.1±10.5) . In conclusion, our study found Bsm gene and ALAD gene influence bone density. However, the mechanism and the exact relationship between two genes and bone density need further investigation.

碩士<br>國立成功大學<br>環境醫學研究所<br>95<br>Both urinary trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (SPMA) are currently suggested as biological exposure indices (BEIs) for benzene exposure by American Conference of Governmental Industrial Hygienists (ACGIH). The BEI values of ttMA and SPMA are 500 and 25 μg/g creatinine, respectively, based on the threshold limit values-time weighted average (TLV-TWA) of 0.5 ppm. According to previous studies show the GST (Glutathione S-transferase) genotype polymorphism can influence the excretion of urinary ttMA and SPMA. Nevertheless, these observations are not consistent in these reports of which the GST genotypes influence the levels of benzene metabolites. These results also revealed that the concentration ratio of urinary ttMA level to SPMA level may be influenced by GST genotype polymorphism. In previous report, CYP2E1 (Cytochrome P450 2E1) genotype may affect the metabolism of benzene. Therefore, the purposes of this study are (1) to investigate the correlation of the urinary benzene metabolites, SPMA and ttMA, to the benzene exposure; (2) to investigate whether different genotypes, including CYP2E1 and GST, can affect the ttMA and SPMA levels and ratio of ttMA to SPMA or not. The urinary ttMA, SPMA level and ttMA to SPMA concentration ratio showed no significant difference among subgroups of CYP2E1 Rsa1 & Pst1 genotype polymorphism. In GST genotype polymorphism, the SPMA levels of GSTT1 positive genotype subjects were higher than the GSTT1 deficient genotype subjects. In addition, the ttMA to SPMA concentration ratios of GSTT1 positive subjects were lower than that of GSTT1 deficient subjects. The data represented that the urinary ttMA excretion levels may be influenced by GSTT1. GSTT1 genotype should be considered as factor of susceptibility for assessment of benzene metabolism.

碩士<br>台北醫學院<br>公共衛生學研究所<br>88<br>In the cancerization process, congenital factors and environmental factors may jointly or separately affect one into the phases of initiation, promotion and progression. Formerly, academic world just only to probe into the environment factors. But under the same exposure, human shows differential susceptibility to diseases. Therefore, our study aims to confer the variation of molecular and enzyme between man to man which inherited. There is a lot of epidemiology data supported that human being increases the probability getting bladder cancer when they were exposed to aromatic amines. In the past, Taiwan dyestuff industries used amounts of intermediate (Benzidine) in the manufacturing process. Consequently, a total of 207 workers in our study were sampled from a dyestuff manufacturing factory which established for 28 years and located at northern part of Taiwan. With the techniques of Polymerase Chain Reaction and Restriction Fragment Length Polymorphism, we discovered the genotype distribution of CYP1A2(-2964 G→A mutant) is W(G)：M(A) = 72.7%：27.3% and NAT1 is 3：4：10：11 = 23%：49%：27%：1.4%. By the way of comparing genotype and DNA ploidy of urothelial cells, we hope to investigate the association between susceptible factors and urothelial cell damage in dyestuff manufacturing workers. As a result of our study exhibit those who carries genotype of CYP1A2 W/W+NAT1 10/10 would influence the DNA ploidy of urothelial cells to become abnormal under the exposure of smoking or benzidine, especially obvious in smoking group. In the modeling analyses, we still found the influence of CYP1A2 W/W+NAT1 10/10 genotype on abnormal DNA ploidy of urothelial cells after adjusted by several confounders, although it is not statistically significant, it still offers us to realize the roles of CYP1A2 and NAT1 in the mechanism of human metabolize aromatic amines.

碩士<br>高雄醫學大學<br>職業安全衛生研究所碩士班<br>95<br>Aims: To investigate the effects of blood lead and other related factors on ALAD activity in lead workers. Methods: In 121 lead workers and 117 reference subjects, the following data were collected from health examination: blood lead, BMI, glucose AC, and Hct. A questionnaire including of demographic data, medical history, smoking and alcohol consumption was completed by each of subjects. ALAD activity was determined by the standardized method of the European Community. ALAD genotyping was using a method of PCR-RFLP. Results: Blood lead levels in lead workers and reference subjects were 19.5 μg/dL (SD = 14.7) and 2.9 μg/dL (SD = 1.9), respectively. Lead workers had significantly lower ALAD activity then reference subjects (42.6 ± 22.4 U/L vs. 64.3 ± 13.8 U/L, P < 0.001). To all subjects, the relationship between blood lead and ALAD activity was expressed with ALAD (U/L) = -1.208 PbB + 66.10 (r = -0.760, P < 0.001). According to the multiple regression results, the following independent variables were significant related to ALAD activity. ALAD activity in females were much lower 8.15 U/L then males (P < 0.001). Blood lead and glucose AC were inversely associated with ALAD activity (P < 0.001), but the effect of blood lead was profound. The regression coefficient (BETA) of blood lead and glucose AC were 1.04 and 0.11, respectively. Individuals with alcohol consumption showed lower ALAD activity (P = 0.049). The possible threshold value of blood lead for ALAD activity was determined around 10 μg/dL. In this study, 229 ALAD1-1 homozygotes (96.2%), 8 ALAD1-2 heterozygotes (3.8%) were identified, and none of ALAD2-2 homozygote was observed. Conclusions: ALAD activity was inhibited by lead sensitively and stoichiometrically, thus ALAD activity may be adopted as a reliable biomarker of lead toxicity in humen.

碩士<br>國立臺灣大學<br>職業醫學與工業衛生研究所<br>90<br>Part I The association between metabolic polymorphisms and cigarette smoking-induced cancers has been documented. However, the role of DNA repair polymorphism in carcinogenesis is less clear. To investigate if the polymorphisms of metabolic traits and DNA repair modulate smoking-related DNA damage, we used sister chromatid exchange (SCE) as a marker of genetic damage to explore the relationship of microsomal epoxide hydrolase (mEH), glutathione S-transferase M1 (GSTM1), and x-ray cross-complementing group 1 (XRCC1) and cigarette smoking-induced SCE. Sixty-one workers without significant exposure to mutagens were recruited. Questionnaires were completed to obtain detailed occupational, smoking, and medical histories. SCE frequency in peripheral lymphocytes was determined using a standard cytogenetic assay and GSTM1, mEH (exon 3, eoxn 4), XRCC1 (codon 399) genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP). Smokers had higher SCE frequency than nonsmokers (8.4 vs. 7.1, p < 0.05). Among workers who had smoked equal to or greater than 10 cigarettes each day, those with XRCC1 Arg/Gln + Gln/Gln had higher SCE frequency than those with XRCC1 Arg/Arg after adjusting for potential confounders (9.0 vs. 7.9, p < 0.05). The interaction of XRCC1 and cigarettes smoked per day on SCE frequency was also observed (p = 0.02). There was no significant interaction between cigarettes smoked per day with GSTM1 and mEH on SCE frequency. Our results support previous epidemiological studies that XRCC1 may play a role in cigarette smoking-induced lung cancer. Part II The presence of mutant Asp13-K-ras protein, p53 overexpression and anti-p53 antibody have been reported to be associated with vinyl chloride monomer (VCM)-related cancers. The aim of this study was to compare the relationship between VCM-induced p53 and K-ras oncoproteins, and to further investigate the role of polymorphisms of metabolic and DNA repair genes on VCM-induced oncoprotein expression. We examined the plasma samples of 218 male workers occupationally exposed to VCM. Plasma mutant p53 protein and anti-p53 antibody were detected with enzyme-linked immunosorbent assay (ELISA), and Asp13-K-ras proteins were detected using enhanced chemiluminescence Western blotting. Genotypes of cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), glutathione S-transferase T1 (GSTT1) and X-ray repair cross-complementing group 1 (XRCC1, exon 10) were identified using the polymerase chain reaction (PCR). The results revealed that the plasma mutant p53 protein was positive in 10.1% of workers, anti-p53 antibody was positive in 5% of workers and Asp13-K-ras protein was positive in 10.1% of workers. High VCM exposure group (>40 ppm-years) had significantly higher mutant oncoprotein (mutant p53 protein, anti-p53 antibody or Asp13-K-ras protein) expression as compared to low VCM exposure group (<40 ppm-years) (OR=2.0, 95%CI=1.0-3.8). Among high exposure workers, subjects with XRCC1 Gln/Gln genotypes demonstrated significantly higher risk of mutant oncoproteins expression as compared to those with XRCC1 Arg/Arg or Arg/Gln variants (OR=8.5, 95%CI=1.9-38.9) after adjusting for potential confounders. Moreover, there was an interaction between VCM exposure and XRCC1 polymorphisms on oncoprotein expression (p=0.06). In our further analysis, amongst low exposure workers, subjects with CYP2E1 c2c2 genotypes demonstrated greater risk than subjects with CYP2E1 c1c1 or c1c2 genotypes (OR=3.1, 95%CI=0.3-37.8). However, there was no interaction between VCM exposure and genotypes of CYP2E1, GSTM1, and ALDH2 on oncoproteins. We found that p53 overexprssion was significantly associated with VCM cumulative dose (OR=2.5, 95%CI=1.0-6.2). After adjusted for smoking, age, drinking, and hepatitis infection, amongst high exposure workers, subjects with XRCC1 Gln/Gln demonstrated significantly greater risk of p53 overexpression than subjects with Arg/Arg or Arg/Gln (OR=17.0, 95%CI=4.3-198.5). Amongst low exposure workers, subjects with CYP2E1 c2c2 genotypes have significantly higher risk than CYP2E1 c1c1 and c1c2 genotypes (OR=19.9, 95%CI=1.6-253.2). Mutant Asp13-K-ras oncoprotein was not associated with VCM cumulative exposure dose; however, it was significantly associated with current high exposure experience within 5 years of sample collection (OR=2.9, 95%CI=1.1-7.9). After further analysis, we found that subjects experiencing high exposure job within 5 years with XRCC1 Gln/Gln had greater risk of K-ras oncoprotein than those with XRCC1 Arg/Arg or Arg/Gln (OR=1.7, 95%CI=0.1-23.3) although didn’t reach statistical significance. Similarly, subjects with ALDH2 1-2 or 2-2 genotypes demonstrated greater risk than those with ALDH2 1-1 genotypes (OR=2.5, 95%CI=0.6-11.2). Further, subjects experiencing high exposure job within 5 years with GSTT1 non-null genotype revealed significantly higher risk than those GSTT1 null type. Our results suggest that mutant p53 protein and mutant K-ras oncoprotein revealed differential expression in VCM-exposed workers. Mutant K-ras oncoprotein was associated with current exposure, and it became undetected when exposure ends. However, mutant p53 protein was associated with cumulative dose. One possible explanation is mutant p53 gene provide selective growth advantage which making mutant p53 protein sustained in the cell persistently. In contratst, K-ras mutants may be demolished by p53 through the apoptosis. Furthermore, the relationship between p53 overexpression and DNA repair gene and metabolic genes was consistent with our previous study, but the association of mutant K-ras oncoprotein and DNA repair gene and metabolic traits are not clear in this study because of small sample size. Therefore, further studies are needed to elucidate the exact mechanism.

碩士<br>國防醫學院<br>公共衛生學研究所<br>92<br>Motor vehicles are an important source of ambient air pollution in urban areas. The emission of traffic exhausts contain carcinogenic agents, such as polycyclic aromatic hydrocarbons (PAHs). Pyrene is commonly found in mixtures of PAHs, and its metabolites, such as 1-hydroxy pyrene (1-OHP) and 1-hydroxy pyrene glucuronide (1-OHP-gluc), can be measured in human urine. Genetic polymorphisms have been suggested to explain interindividual differences in the PAHs metabolizing enzymes. The aim of present study was to evaluate the influence of genetic polymorphisms on the urinary excretion of PAHs metabolite. A cross sectional study of 45 highway toll station workers and 27 office workers in Taipei was used to evaluate the influence of CYP1A1 (Ile462Val), UGT1A7 (Trp208 Arg) and GSTM1 (non-null/null) genetic polymorphisms on the urinary excretion of 1-OHP -gluc. Demographic variables and risk factors were collected by the questionnaire and daily diary. We used polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and synchronous fluorescence spectroscopy (SFS) to detect genetic polymorphisms and the intensity of 1-OHP-gluc in urine. Univariate and linear regression analysis were used to examine the relation between genetic polymorphisms and urinary 1-OHP-gluc. After exclude the smokers, the mean urinary 1-OHP-gluc concentrations were statistically different between highway toll station workers and office workers (p = 0.027). The amount of the exposure of PAHs was not correlated with urinary 1-OHP-gluc among highway toll station workers. After we stratified as bus/truck lane and car lane categories, there was a borderline significance among car lane (r = 0.473, p = 0.055). The use of mask had protective effect only in highway toll station workers with low PAHs exposure. In the linear regression model, smoking was a dominant factor which was statistically significant correlated with urinary 1-OHP-gluc (p＜0.001). The genotype of GSTM1 was a borderline significantly determined urinary 1-OHP-gluc excretion (p = 0.094). The urinary 1-OHP-gluc excretion in GSTM1 (null) smokers was higher than that in GSTM1 (non-null) smokers (p = 0.023), and there was a interaction between smoking and GSTM1 (p = 0.002). The inducible effect of GSTM1 (null) was only on CYP1A1 (Ile/Ile) (p = 0.048). In the present study GSTM1 on the indirect way of pyrene metabolize to 1-OHP- gluc, the influence of urinary 1-OHP-gluc of GSTM1 on interaction with smoking and the inducibility of CYP1A1 which probably played a more and important role.

碩士<br>高雄醫學大學<br>公共衛生學研究所<br>101<br>Background and Purpose: Lead are one of the most toxic heavy mentals.The mental lead is widely used in our life and in the industry.Popele may expose to lead not only in the job but also in the life.Exposed to lead is harmful various organs in human.Several lines of evidence have indicated that Pb is able to stimulate the expression of tumor of necrosis factor-alpha(TNF-α).Previous reports indicate that Pb2+ can entry into cells by activating mediators of inflammation vis the plasma membrane EGFR,and by store-operated Ca2+ channel(SOC).Thus,we investigate the association among EGFR/ORAI1(the key subunit of store-operated Ca2+ channel) gene polymorphisms,blood lead levels,and serum TNF-alpha. Materials and Methods: The present study included 426 lead-exposed subjects and controls in Taiwanese population.The questionnaire and blood sample collected information about demographic characteristics,biochemical data,blood lead levels,and serum TNF-α levels.DNA was also extracted for Genotyping. Genotyping was performed using TaqMan® SNP Genotyping Assays.The EGFR 3 SNPs (rs763317,rs2280653,rs2072454) and ORAI1 5 SNPs (rs712853,rs6486795,rs12313273,rs12320939,rs7135617) were genotyped in all subjects. Results: First,we divided blood lead levels into four groups (0≦BPb≦5, 5< BPb≦10, 10< BPb≦30 ,and BPb>30).After analysing,we found that serum TNF-α levels increased with blood lead levels.And then,using multiple regression analysis.After adjusting potential confounder,the association with blood lead levels and serum TNF-α levels was found.When blood lead levels increased 1μg/dL,serum TNF-α levels increased 0.34~0.38pg/mL.Two of ORAI1 SNPs(rs712853 and rs12313273)effected the lead-induced TNF-α expression. After adjusting blood lead levels and other confounder,the CT genotype of rs712853 polymorphism had significantly decreased the level of TNF-α 3.20(SE=1.39)pg/mL compared with the TT genotype. The CC genotype of rs712853 polymorphism had decreased the level of TNF-α 3.32(SE=2.15)pg/mL compared with the TT genotype.The CT genotype of rs12313273 had significantly increased the level of TNF-α 2.77(SE=1.36)pg/mL compared with the TT genotype. The CC genotype of rs12313273 polymorphism had increased the level of TNF-α 1.07(SE=2.18)pg/mL compared with the TT genotype.But all three EGFR SNPs were not. Conclusions: We showed that two of ORAI1 SNPs were associated with blood lead levels and serum TNF-α levels in Taiwanese population.

碩士<br>高雄醫學大學<br>公共衛生學系職業安全衛生碩士班<br>103<br>Background and objective: Lead had neurotoxicity in peripheral sensory systems. Variant vitamin D receptor (VDR) genes and polymorphisms of Metallothioneins (MTs) were associated to lead toxicity. But no relationship between lead neurotoxicity and polymorphisms were discussed before. This study investigated the relationship among the polymorphisms of the VDR, MT1A, MT2A and lead toxicity to sensory nervous system in chronic lead – exposed workers Methods: We measured 181 workers’ vibration perception thresholds (VPT) and current perception thresholds (CPT) as neurological outcomes since 1990~1995. The outcome variables were then correlated to the subject’s index of long-term lead exposure that was calculated by the subject’s serial blood lead data in a period of working duration. The polymorphisms of VDR (Bsm rs1544410, Apa rs7975232 and Taq rs731236), MT1A (rs11640851 and rs8052394) and MT2A (rs10636 and rs28366003) are defined. The potential confounders, including age, gender, body height, smoking, alcohol consumption and working life span, were also collected and analyzed in linear regressions. Results: The regression coefficients of some gene polymorphisms were at lease 20 times larger than regression coefficients of TWICL. The regression analyses showed MT2A rs28366003(AG/AA) had significant different in all neurological outcomes except foot VPT and had the negative regression coefficients. All regression coefficients of TWICL mildly increased at the same time. MT1A rs11640851 (AA/CC) had significant difference in all neurological outcomes except hand and foot VPT. MT1A rs8052394 (GG/AA) had significant difference in hand and foot CPT 2000Hz. In MT2A rs10636, more C allele showed more influence in all three frequency of hand CPT. Among VDR, Apa rs7975232 (CC/AA) had most difference in all three frequency of hand CPT. Conclusion: TWICL needed to increase at lease 20μg/dL to have the same influence on neurotoxicity comparing with some different gene polymorphisms. Individuals with AG genotype for MT2A rs28366003 had neural protective effects by increasing sensitivity. CC genotype for Apa (rs7975232) of VDR and CC genotype for MT2A rs10636 increased the neurotoxicity on CPT more significant on hands. MT1A rs8052394 GG genotype has the protective effect on large myelinated nerve. MT1A rs11640851 AA genotype has susceptibilities to neurotoxicity. The interaction between zinc and lead to neurotoxicity needs further studies.

碩士<br>高雄醫學大學<br>醫學研究所<br>99<br>Introduction and aims : The lead-induced injury is multiple organs in human, which the factors of the injury was considered oxidative stress, inflammation and functional NO deficiency. Some studies have shown that TNF-alpha?ncan induce extra-reactive oxygen species which are related with oxidative stress and inflammation. The aim of this study is to investigate the effects of oxidative stress, inflammation induced by lead exposure among the different types of TNF-alpha?? promoter polymorphisms. Methods : The lead-exposed subjects came from a lead factory and the controls collected from the public but no lead exposed. The blood lead levels were evaluated by AAS(Atomic Absorption Spectrophotometer) assay. The serum TNF-alpha???nlevels were detected by ELISA. The TNF-alpha?npromoter polymorphisms were analyzed by Specific primer-probes to run Real-Time PCR. Results : In this study, the lead-exposed subjects had higher blood lead levels and serum TNF-alpha?nlevels than those of the controls. The polymorphisms of the lead-exposed subjects and the controls were not significantly different. Dividing into 4, the highest blood lead level group had significantly higher serum TNF-alpha?nlevel. But The polymorphisms of the all groups of blood lead levels were not significantly different. With the multiple regression model, the rise of serum TNF-alpha?nlevel was only associated with the increased blood lead levels and the decreased BMI level. Discussion : The study has shown that exposure to lead induced TNF-alpha?nbut the TNF-alpha?npromoter polymorphisms did not effect the lead-induced TNF-alpha?nexpression. However, the other polymorphisms could effect the mechanism, which need further investigation.

Background: Shift work has recently been identified as a breast cancer risk factor, where meta-analysis has indicated an approximately 50% increased risk among long-term shift workers. However, additional studies with more comprehensive methods of shift work exposure assessment are needed to capture the diversity of shift patterns. The hypothesized mechanism for this relationship involves chronodisruption (altered circadian rhythms), where increased exposure to light at night during night shifts may decrease production of the cancer-protective hormone melatonin. Further, coordination of circadian rhythms, including melatonin production, is governed by the interactions of a set of central clock genes. Recent studies have suggested that variants in clock genes are associated with cancer risk at multiple sites, including breast cancer, although few studies have considered potential interactions with shift work. Methods: This thesis examined relationships of both shift work and clock gene polymorphisms (and their interactions) with breast cancer risk in a case-control study of 1,142 cases and 1,178 controls. The association between light exposure and melatonin production was also investigated in a longitudinal biomarker study conducted among 123 nurses working a two-day, two-night rotating shift pattern. Results: In the case-control study, an association between breast cancer and ≥30 years of shift work (OR = 2.20, 95%CI = 1.13 – 4.28) was detected, although no relationship with short (0 – 14 years) or medium (15 – 29 years) term shift work was observed. As well, variants in 14 clock-related genes were not associated with breast cancer and there were no apparent interactions with shift work history. In the biomarker study, both peak melatonin levels and daily change in melatonin levels were similar when nurses were working their day and night shifts. Further, on the night shift, a slight inverse relationship between light and change in melatonin was observed (p = 0.04). Conclusions: Taken together, these results contribute to the understanding of both the association between shift work and breast cancer, and the biologic mechanisms underlying this relationship. Since shift work is required for many occupations, understanding the mechanisms through which it impacts breast cancer is important to the development of healthy workplace policy.<br>Thesis (Ph.D, Community Health & Epidemiology) -- Queen's University, 2012-09-26 20:59:40.209

碩士<br>國立陽明大學<br>公共衛生研究所<br>93<br>Coke-oven workers (COWs) are occupationally exposed to high concentrations of polycyclic aromatic hydrocarbons (PAHs), especially workers near the topside of the oven. Uninary 8-hydroxy-2-deoxyquanosine (8-OH-dG) and 1-hydroxypyrene (1-OHP) are biomarkers of oxidative DNA damage and PAH metabolism, respectively. Previously, we found that glycine N-methyltransferase (GNMT) can bind benzo(a)pyrene (BaP) and inhibit DNA adducts formation. Since methionine synthase (MS), 5,10-methylene- tetrahydrofolate reductase (MTHFR) and GNMT are involved in the one-carbon metabolism pathway, we would like to study the associations of the genetic polymorphisms of these genes and the urinary biomarkers in coke-oven workers. Questionnaires and lymphocyte DNA were collected from 217 coke-oven workers which including 54 workers from the topside of the oven (high exposure group, group A) ,92 workers from both sides of the oven (medium exposure group, group B) and 71 administrative persons from the same factory (low exposure group, group C). Three genotypes of GNMT-SNP1, INT/DEL, and STRP1 were analyzed using TagMan and GeneScan methods; both A2756G genotype of MS gene and C677T genotype of MTHFR gene were analyzed using PCR-RFLP. Results：The preliminary results indicate that there is a reverse relationship between the urinary levels of 1-OHP and 8-OH-dG in the group A workers with different GNMT genotypes. Use logistic regression analysis indicated that workers with GNMT STRP1-B/B genotypes had higher 8-OHdG level than those with STRP1-A/A or A/B genotype in the group A (OR= 4.41, 95%CI =1.04-18.81, p= 0.044, respectively).For the GNMT haplotype study, workers with SNP1+INS-DEL+STRP1-C/T+INS/INS+A/A had lower 8-OHdG level than those with SNP1+INS-DEL+STRP1-C/T + INS/DEL + B/B in group A（7.6 ± 7.3 ng/ml < 32.9 ± 26.8 ng/ml, p = 0.01）. In conclusion, GNMT may have a protective effect against the exposure to carcinogens such as PAHs, and the interactions of the genetic polymorphisms of GNMT, MS, MTHFR were associated with different 1-OHP and 8-OHdG level in coke-oven workers. This study may be useful for the genetic counseling of workers who expose to environment carcinogens related to PAHs.