Ruey-Hong Wong

The Presence of Human Papillomavirus Type 16/18 DNA in Blood Circulation May Act as a Risk Marker of Lung Cancer in Taiwan

Lung cancer is the leading cause of cancer death in Taiwan, and the paucity of dependable risk markers has impeded the early management of lung cancer. An association of human papillomavirus (HPV) 16/18 infection with lung cancer among nonsmoking Taiwanese women was revealed in our previous study.

Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers

Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. VCM may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferases (GSTs). Thus workers with inherited variant metabolic enzyme activities may have an altered risk of genotoxicity. This study was designed to investigate which risk factors might affect sister chromatid exchange (SCE) frequency in polyvinyl chloride (PVC) workers. Study subjects were 44 male workers from three PVC factories. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. SCE frequency in peripheral lymphocytes was determined using a standardized method, and CYP2E1, GSTM1, GSTT1 and ALDH2 genotypes were identified by the polymerase chain reaction (PCR). Analysis revealed that smoking status and exposure to VCM were significantly associated with increased SCE frequency. The presence of ALDH2 1-2/2-2 genotypes was also significantly associated with an elevation of SCE frequency (9. 5 vs. 8.1, p<0.01). However, CYP2E1, GSTM1 or GSTT1 genotypes were not significantly associated with SCE frequency. When various genotypes were considered together, combination of CYP2E1 c1c2/c2c2 with ALDH2 1-2/2-2 showed an additive effect on SCE frequency. Similar results were also found for the combination of smoking with CYP2E1, or smoking with ALDH2. These results suggest that VCM workers with ALDH2 1-2/2-2 genotypes, who also smoke, may have increased risk of DNA damage.

GSTP1 genetic polymorphism is associated with a higher risk of DNA damage in pesticide-exposed fruit growers

Pesticide exposure is associated with various neoplastic diseases and congenital malformations. Animal studies also indicated that pesticides may be metabolized by cytochrome P450 3A5 (CYP3A5) enzymes, paraoxonases (PON1 and PON2), or glutathione S-transferases (GSTM1, GSTT1, and GSTP1). However, little is known about the genotoxicity of pesticides in people with various genetic polymorphisms of human CYP3A5, PON1, PON2, GSTM1, GSTT1, and GSTP1. Thus, this study was designed to investigate whether various metabolic genotypes are more susceptible to DNA damage in pesticide-exposed fruit growers. Using the Comet assay, the extent of DNA damage was evaluated in the peripheral blood of 91 fruit growers who experienced pesticide exposure and 106 unexposed controls. Questionnaires were administered to obtain demographic data, cigarette smoking habits, medical, and occupational histories. The genotypes for CYP3A5, PON1, PON2, GSTM1, GSTT1, and GSTP1 genes were identified by PCR. The results showed that subjects experiencing high or low pesticide exposure had a significantly greater DNA tail moment (DAN damage) than did controls. The multiple regression model also revealed that age (P < 0.01), high pesticide exposure (P < 0.01), low pesticide-exposure (P < 0.01), and CYP3A5 (P = 0.04) and GSTP1 (P = 0.02) genotypes were significantly associated with an increased DNA tail moment. Further analysis of environmental and genetic interactions revealed a significant interaction for GSTP1 genotypes to influence DNA tail moment for the high pesticide exposure group. These results suggest that individuals with susceptible metabolic GSTP1 genotypes may experience an increased risk of DNA damage elicited by pesticide exposure. (Cancer Epidemiol Biomarkers Prev 2006;15(4):659–66)

An increased standardised mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan

Aims: To determine the standardised mortality ratio (SMR) corresponding to different causes of death in workers from polyvinyl chloride polymerisation factories in Taiwan. Methods: Retrospective cohort study of workers from six polyvinyl chloride polymerisation factories in Taiwan. A total of 3293 male workers who had been employed for at least one year during the period 1 January 1950 to 31 December 1992, and were alive on 1 January 1985 were included for analysis. Using data acquired from Taiwans National Mortality Registry, it was found that 144 of these workers died during the period 1985–97. The follow up rate was 99% with a total number of person-years at risk of 40 557. Results: SMR for all causes of death was 0.78, indicating a possible “healthy worker” effect. The SMR for liver cancer decreased with increasing age of first exposure to vinyl chloride monomer. This association was more prominent for workers who were first employed in the industry prior to 1970 (SMR 4.82). Medical records indicated that most liver cancers in this study were hepatocellular carcinoma. Conclusions: Polyvinyl chloride workers may experience a higher risk of developing liver cancer, particularly hepatocelluar carcinoma.

Accumulation of chromium and nickel metals in lung tumors from lung cancer patients in Taiwan.

Metallic carcinogenicity is generally thought to generate of free radicals, and thus some metals were reported to play a role in lung tumorigenesis. In order to verify the role of heavy metals in the development of Taiwanese lung cancer, a case-control study was conducted to compare heavy metal contents between 60 tumor and 42 normal lung tissues surgically resected from lung cancer and noncancer patients. The tissue concentration of heavy metals, including cadmium (Cd), chromium (Cr), cobalt (Co), lead (Pb), and nickel (Ni), was measured using by atomic absorption spectrometry (AAS). Our results indicated that Cr and Ni contents in lung tumors of lung cancer patients were significantly higher than those in normal lung tissue of noncancer controls, but Co content was markedly lower in lung tumors. Additionally, Pb content in lung tumors was associated with nodal involvement, and Co amounts in squamous-cell carcinomas were relatively higher than those in adenocarcinomas. Data suggest that accumulation of Cr and Ni in lung tumors may play a role, at least in part, in the development of lung cancer in Taiwan.

Association of hepatitis virus infection, alcohol consumption and plasma vitamin A levels with urinary 8-hydroxydeoxyguanosine in chemical workers

Urinary 8-hydroxydeoxyguanosine (8-OHdG) DNA adduct has been used as a biomarker in epidemiological studies. However, the determinants for urinary 8-OHdG have not been clearly identified. We tested urinary 8-OHdG levels in 205 male workers who had been exposed to vinyl chloride monomer (VCM). Epidemiological information was obtained by an interviewer-administered questionnaire. Hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV) were also determined by immunoassay. Plasma antioxidants including Vitamins A and E, alpha- and beta-carotenes were assayed by high performance liquid chromatography. Median of urinary 8-OHdG level was 9.8 ng/mg creatinine (range, 1.4-60.1). Multiple linear regression analysis showed that alcohol drinkers had higher urinary 8-OHdG than those who did not, but there was no dose-response between the amount of alcohol consumption and urinary 8-OHdG. Workers with positive HBsAg, anti-HCV and elevated plasma Vitamin A level were independently associated with higher levels of urinary 8-OHdG, whereas age, smoking, body mass index, plasma alpha- and beta-carotenes, Vitamin E levels, or VCM exposure did not show such an association. The results suggest that active inflammation of hepatitis B and C, alcohol consumption and higher Vitamin A level can induce oxidative stress. Thus, we conclude that potential determinants need to be considered in epidemiological studies when urinary 8-OHdG is used as a biomarker.

Evaluation of internal consistency and re-test reliability of Bath ankylosing spondylitis indices in a large cohort of adult and juvenile spondylitis patients in Taiwan

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G) have been recommended for evaluating function and disability in patients with ankylosing spondylitis (AS). The aim of this study was to develop a Chinese version of the BASDAI, BASFI, and BAS-G and assess their reliability and validity. The Chinese version was obtained after a translation and back-translation process. A total of 447 patients with adult and juvenile AS were assessed using these three instruments. Reliability was tested by internal consistency and test–retest reliability. Internal consistency of the instrument was given as Cronbach’s alpha. Test–retest reliability was assessed by intraclass correlation coefficient. To assess the sensitivity to change, 153 patients were included in an 8-week follow-up study. In our analysis, the reliability of these three instruments—the BASDAI, BASFI, and BAS-G—for a 24-h test–retest showed acceptable intraclass correlation coefficients (0.92–0.94). Our Chinese versions of the BASDAI, BASFI, and BAS-G also showed 0.87, 0.94, and 0.90, respectively, with Cronbach’s alpha coefficient, indicating good reliability. For sensitivity to change in 8-week follow-up, all three instruments showed 5.0 to 5.4% changes. Our Chinese versions of the BASDAI, BASFI, and BAS-G showed adequate reliability, validity, and responsiveness to clinical change. Thus, disease activity and functional status in Chinese-speaking patients with AS may be adequately evaluated with these versions of the original instruments.

Association of IL-12B genetic polymorphism with the susceptibility and disease severity of ankylosing spondylitis.

Objective. Interleukin 23 (IL-23) stimulates the differentiation of T helper 17 (Th17) cells, which are involved in the pathogenesis of ankylosing spondylitis (AS). Binding of IL-23 to the IL-23 receptor complex activates Janus kinases 2 and tyrosine kinase 2, which phosphorylate IL-23R and subsequently promote the transcription of the IL-17 gene. IL-12B encodes a p40 subunit common to IL-12 and IL-23. We evaluated the effects of IL-12B and IL-23R genotype on the occurrence and clinical features of AS. Methods. A total of 362 patients with AS and 362 healthy controls were enrolled in the study. Genotypes of IL-12B A1188C (rs3212227) and IL-23R C2370A (rs10889677) were identified by polymerase chain reaction/restriction fragment-length polymorphism. Disease activity and functional status were assessed by Bath AS indices. Results. Subjects carrying IL-12B CC [matched relative risk (RRm) 1.93, 95% CI 1.23–3.03] and IL-12B AC (RRm 1.73, 95% CI 1.21–2.46) genotypes had a significantly greater risk of developing AS than subjects with the IL-12B AA genotype. Subjects carrying both IL-12B CC and IL-23R AA genotypes also had a significantly higher risk (RRm 2.98, 95% CI 1.51–5.89) of developing AS compared to those with IL-12B AA and IL-23R CC/CA genotypes, and this interaction between IL-12B and IL-23R was significant. Patients with AS who had IL-12B CC and IL-12B AC genotypes had an obviously increased Bath Ankylosing Spondylitis Disease Activity Index score compared to those who carried the IL-12B AA genotype (4.3 vs 3.7). Conclusion. The IL-12B A1188C genotype was associated with the development and disease severity of AS.

Chinese herbal medicine, sibship, and blood lead in children

OBJECTIVES: Risk factors for increased blood lead concentration (BPb) has been investigated. However, the effect of sibship and Chinese herbal medicine on BPb has not been systematically studied. In this study BPb data from voluntary testing was used to determine if Chinese herbal medicine and sibship were associated with BPb. METHODS: 319 children aged 1-7 were tested for BPb. Meanwhile, parents were interviewed to obtain information including consumption of Chinese herbal medicine, living environment, lifestyle, and sibship of the children tested. RESULTS: The mean (SD) BPb of 319 preschool children was 4.4 (2.4) micrograms/dl. The consumption of Ba-baw-san (a Chinese herbal medicine) was significantly associated with increased BPb in children (p = 0.038). Further multivariate regression analysis of BPb in 50 pairs of siblings showed the factors of being brothers explained 75% of variation for BPb, and being sisters and brother-sister explained 51% and 41% of variation respectively. CONCLUSION: Chinese herbal medicine and childrens play patterns within the family expressed in different types of sibship are the main determinants of low concentrations of BPb in preschool children of Taiwan.

Comparison of Source Identification of Metals in Road-Dust and Soil

Source identification of toxic metals is very critical for pollution prevention and human health protection. Many studies only use either road dust metal data or soil metal data to evaluate metal contamination and identify pollution sources, and this may lead to the exclusion of some important information. In this study, the differences of metal spatial distribution and source identification between road dust and associated soil in an industrial area were investigated. Results indicate the metal concentrations in road dust were generally higher than those in soil. Based on the average concentrations, the order for dust metal concentrations was Fe>>Zn>>Pb>Cu>Cr>Ni. The order for soil metal concentrations was slightly different, namely Fe>>Zn>>Cu∼Pb>Ni>Cr. The spatial distributions of metals in the road dust were very different from those in the soil, except for Fe. The GIS results indicate that elevated levels of Fe, Zn, and Pb were present in road dust near a steel plant. High concentrations of Cu, Cr, and Ni appeared at a road intersection. Elevated metal concentrations of Fe, Zn, Pb, Cu, and Cr were present in soil around the steel plant. A coal-fired power plant did not seem to be a significant metal source in this study. Significant correlations for dust metals imply that these were well mixed in the study area. The metal sources identified by PCA with soil metal data were obviously different from those identified with road dust metal data. When road dust metal data were used, the changes of PCA analyzed areas slightly influenced the source identification. The PCA results were obviously influenced by changes of analyzed areas when soil metal data were used.