Biomedical subjects

L L Hsieh

Publications and source records attributed to L L Hsieh.

At least 37 records · Page 2Linked to original sources

PubMed1999

Increased chromosome-type chromosome aberration frequencies as biomarkers of cancer risk in a blackfoot endemic area.

To examine whether biomarkers such as sister chromatid exchanges (SCEs) and chromosome aberrations (CAs) can predict cancer development, a nested case-control study was performed in a blackfoot endemic area with a known high cancer risk. A cohort of 686 residents was recruited from three villages in the blackfoot endemic area. Personal characteristics were collected, and venous blood was drawn for lymphocyte culture and stored in a refrigerator. The vital status and cancer development were followed using the National Death Registry, Cancer Registry, and Blackfoot Disease Registry. The follow-up period was from August 1991 to July 1995. During this 4-year period, 31 residents developed various types of cancer. Blood culture samples from nine of these subjects were unsuitable for experiments due to improper storage. Finally, a total of 22 cancer cases had cytogenetic samples that could be analyzed. Twenty-two control subjects were selected from those who did not develop cancer in the study period, and these subjects were matched to cases by sex, age, smoking habits, and residential area. The results showed that there was no significant difference in the frequencies of SCE and chromatid-type CAs between the case and control groups. However, the frequencies of chromosome-type CAs, e.g., chromosome-type gaps, chromosome-type breaks, chromosome-type breaks plus exchanges, total chromosome-type aberrations, and total frequencies of CAs in the case group, were significantly higher than those in the control group (P < 0.05). The odds ratio of cancer risk in subjects with more than zero chromosome-type breaks was 5.0 (95% confidence interval = 1.09-22.82) compared to those with zero chromosomal breaks. The odds ratios for more than zero chromosome-type breaks plus exchanges and a frequency of total chromosome-type aberrations of >1.007% were 11.0 and 12.0, respectively (P < 0.05). Subjects with a total CA frequency of >4.023% had a 9-fold increase for cancer risk. These results indicate that chromosome-type CAs are good biomarkers for the prediction of cancer development, whereas SCEs and chromatid-type CAs cannot predict cancer risk.

Adult↗

PubMed1999

Glutathione S-transferase (GST) M1 and GST T1 genotypes and hematopoietic effects of benzene exposure.

This study investigated whether or not the genotypes glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with low white blood cell (WBC) count found in benzene exposed workers. We found that individuals with genotypes positive for both GST T1 and GST M1 showed the highest prevalence of low WBC [odds ratio (OR) = 4.67, P = 0.046, 95% confidence interval (CI) = 1.02-24.15] when the benzene exposure was high. Multiple logistic regression showed that benzene exposure (OR = 2.81, P = 0.062, 95% CI = 0.96-8.30) was associated with increased OR on low WBC and interactions between the benzene exposure and the genotype of GST T1 were also observed. These observations suggest that GST T1 and GST M1 may play important roles in the biotransformation of benzene, the effect which leads to its hematotoxicity.

Benzene↗

PubMed1998

Absence of APC gene mutation in the mutation cluster region in hepatocellular carcinoma.

APC gene mutations have been demonstrated not only in colorectal carcinoma but also in a variety of human cancers. To define the possible role of mutations of the APC gene in hepatocarcinogenesis, we examined 46 pairs of hepatocellular carcinomas and corresponding non-tumorous liver tissue by polymerase chain reaction and single strand conformation polymorphism. All 46 hepatocellular carcinomas had no altered electrophoretic mobility to suggest the presence of APC gene mutation in the mutation cluster region. We also examined the possible loss of heterozygosity of APC and MCC gene loci by fragment length polymorphism analysis and by polymerase chain reaction. None of the cases showed a loss of heterozygosity at the APC and MCC gene loci. The results suggested that the possibility of APC and MCC as the gene defect in the genesis of human hepatocellular carcinoma may be very rare.

Adult↗

PubMed1998

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.

Adult↗

PubMed1998

Frequency of Epstein-Barr virus-associated gastric adenocarcinoma in Taiwan.

Eighty-two gastric adenocarcinomas (32 intestinal and 50 diffuse type) were investigated for the presence of Epstein-Barr virus (EBV) DNA by amplifying the 78-bp fragment from the EBNA1 gene with polymerase chain reaction. EBV was detected in 17 (20.7%) of the 82 gastric tumorous specimens. Of these 17 EBV-positive cases, only one was EBV-positive in the adjacent non-tumorous tissue. EBV-positive gastric adenocarcinoma was present in 15.6 and 24.0% of the intestinal and diffuse type tumors, respectively, but within the two classes there was significant non-homogeneity by type. EBV was found more frequently in adenocarcinomas of the tubular (25%) and poorly differentiated (30.3%) types. EBV involvement was found more in male than in female patients. Eighty of the 82 tumors were also checked for the prevalence of p53 gene mutation. Of the 17 EBV-positive gastric adenocarcinomas, only two showed p53 gene mutations. The p53 mutation rate was lower in EBV-positive tumors (11.8%) than in EBV-negative tumors (25.4%).

Adenocarcinoma↗

PubMed1998

Hepatocellular carcinoma complicated with coexisting hepatolithiasis: pitfalls in diagnosis and management.

Nineteen patients with hepatocellular carcinoma associated with hepatolithiasis were retrospectively analyzed. Eleven of the 19 patients presented with hepatolithiasis-related biliary infection. Diagnosis was erroneously assumed to be hepatolithiasis alone, liver abscess, or cholangiocarcinoma in five of 11 patients before surgery was attempted. Middle-age, male sex, liver cirrhosis, hepatitis B or C infection, abnormal alpha-fetoprotein, and negative carcinoembryonic antigen raised the suspicion of associated hepatocellular carcinoma rather than cholangiocarcinoma in patients with hepatolithiasis. Antibiotics and nonoperative methods to resolve biliary infection first, followed by hepatectomy, in selected cases, to eradicate hepatocellular carcinoma and hepatolithiasis simultaneously provides the best chance for long-term survival. Otherwise, patients often died of hepatolithiasis-related biliary sepsis rather than hepatocellular carcinoma per se in the long run.

Adult↗

PubMed1998

Lung function and general illness symptoms in a semiconductor manufacturing facility.

Large quantities of potent gases, dopants, photoactive chemicals (photoresists, photoinitiators), solvents, and ionizing radiation are used in the semiconductor manufacturing process, but little is known about the occurrence of respiratory disease from exposures in this industry. The purpose of this study was to assess the pulmonary risk by conducting pulmonary function tests and symptoms survey in a semiconductor plant in Taiwan. This study is part of a clinical survey conducted on 926 workers in a semiconductor plant in Taiwan in July 1995. The study items included a standard self-administered questionnaire, chest x-rays, pulmonary function tests, and physical examinations in 249 workers. There was a borderline significance of higher prevalence (P = 0.06) of restrictive lung abnormality in male photolithographic workers (4 of 21; 19.1%) than in male control workers (0 of 17; 0%), and the smoking- and age-adjusted odds ratio was 4.1 (95% confidence interval [CI], 0.41-41.6). There was a significantly higher prevalence (P = 0.02) of restrictive lung abnormality in male ion-implantation workers (5 of 19; 26.3%) than in male control workers (0 of 17; 0%), and the smoking- and age-adjusted odds ratio was 3.7 (95% CI, 0.52-26.7). There were significantly higher prevalences of airway irritation, eye irritation, headache, stress, tiredness, and poor memory in female photolithographic or etch/diffusion workers than in control workers. This study suggests that restrictive lung abnormality is a potential health effect in male silicon-wafer fabrication workers in the semiconductor industry. The tasks of male process, maintenance, and equipment engineers put them at risk for intermittent short-term peak exposure. This may account for a higher prevalence of mild restrictive lung abnormality among male engineers of photolithographic and ionimplantation sections. The findings of this medical surveillance are tentative, but they suggest that further investigation of the etiologic factors and the subsequent health effects is necessary.

Adult↗

PubMed1997

The GST T1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function.

Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylene oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) correlated with abnormal liver function found in vinyl chloride exposed workers. For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups (high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alanine aminotransferase (ALT) was used as the parameter of liver function. The genotypes CYP2E1, GST T1 and GST M1 were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes CYP2E1, GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positive GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly associated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of which leads to liver damage.

Adult↗

PubMed1997

Arsenic methylation capacity, body retention, and null genotypes of glutathione S-transferase M1 and T1 among current arsenic-exposed residents in Taiwan.

In order to elucidate the relationships among arsenic methylation capacity, body retention, and genetic polymorphisms of glutathione S-transferase (GST) M1 and T1, a total of 115 study subjects were recruited from Lanyang Basin located on the northeast coast of Taiwan. Specimens of drinking water, blood, urine, hair and toenail were collected from each study subject. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic absorption spectrometry. Arsenic concentration in hair and toenail were quantitated by atomic absorption spectrophotometry. The polymerase chain reaction was used to determine genetic polymorphisms of GST M1 and T1. Arsenic concentrations in urine, hair, and toenail of study subjects were positively correlated with arsenic levels in their drinking water. Percentages of various arsenic species in urine (mean +/- standard error (SE) were 11.8 +/- 1.0, 26.9 +/- 1.2 and 61.3 +/- 1.4, respectively, for inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Men and women had similar arsenic methylation capability. No associations were observed between arsenic methylation capability and arsenic content in either drinking water or urine. Ratios of arsenic contents in hair and toenail to urinary arsenic content (mean +/- standard error) were 6.2 +/- 0.7 and 16.5 +/- 1.7, respectively. Genetic polymorphisms of GST M1 and T1 were significantly associated with arsenic methylation. Subjects having the null genotype of GST M1 had an increased percentage of inorganic arsenic in urine, while those with null genotype of GST T1 had an elevated percentage of DMA in urine. Arsenic contents in hair and toenail were significantly correlated with the increase in arsenic concentrations of drinking water and urine, while no significant associations were observed between arsenic contents in hair and toenail and polymorphisms of GST M1 and T1. The relationship between arsenic methylation capability and body retention was modified by genetic polymorphisms of GST M1 and T1. Arsenic contents in hair and toenail were negatively associated with MMA percentage and positively associated with DMA percentage among subjects having null genotypes of GST M1 and T1, but not among those with non-null genotypes.

Arsenic↗

PubMed1996

p53 gene mutation in cerebral primitive neuroectodermal tumor in Taiwan.

p53 mutation has been rarely reported in cerebral primitive neuroectodermal tumors (PNET). To determine the significance of p53 mutations in the development of cerebral PNET, we studied cerebral PNET samples from 14 patients, 8 females and 6 males with a mean age of 38 years (range 10 months to 77 years) who had total or subtotal surgical resection. Histological typing of PNET with neuronal (N) and non-neuronal (NN) differentiation groups revealed 8 and 6 cases, respectively. Six (43%) of the 14 patients had p53 mutation. The p53(+) and p53(-) groups had an age range of 19-77 with a mean of 49 years and 10 months to 57 years with a mean of 30 years, respectively. p53 expression between the PNET-N and PNET-NN groups was 5 of 8 (62.5%) and 1 of 6 (16.7%), respectively. The mutations contained 3 transitions, 2 transversions and 1 frameshift; none of them occurred at the site of 'hot-spot' residues (codons 175, 248, 273). The results suggest that: (1) p53 mutation in cerebral PNET tends to show a higher incidence of neuronal differentiation and occurs in the older age group in Taiwan, (2) there was no difference in survival time between the PNET-N and PNET-NN groups (7 months and 6 months) (P = 0.54), and between p53(+) and p53(-) groups (6 months and 7 months) (P = 0.57), and (3) PNET may be an entity of a heterogenous group of tumors with different genetic mechanisms controlling their trends of differential lineage. Further studies are needed to determine the significance of p53 mutations in PNET development, especially the role of carcinogens in the genesis of PNET in Taiwan.

Adolescent↗

PubMed1996

L-myc, GST M1 genetic polymorphism and hepatocellular carcinoma risk among chronic hepatitis B carriers.

In order to assess associations between the genetic polymorphism of L-myc and glutathione S-transferase M1 (GST M1) and the risk of hepatocellular carcinoma (HCC), a total of 46 surgically treated HCC patients who were seropositive in hepatitis B surface antigen (HBsAg) and 88 HBs-Ag positive controls were recruited for this study. L-myc and GST M1 genetic polymorphism was examined using a polymerase chain reaction-based restriction fragment length polymorphism assay on DNA extracted from liver and peripheral blood samples. There was no significant difference in GST M1 genotypes between HCC patients and matched controls. A gene dosage trend of association with HCC risk was observed for L-myc genotype. The dose-response relationship remained statistically significant in the multiple logistic regression analysis.

Age Factors↗

PubMed1996

p53 gene mutation in thyroid carcinoma.

The pattern of p53 protein expression was examined in 92 cases of thyroid carcinoma. When the cases were divided into two groups with regard to their cytoplasmic staining only or nucleus staining only, the frequency of the nucleus staining group was significantly higher in the poorly differentiated carcinoma (PDC) and undifferentiated carcinoma (UDC) groups (10.5% and 25%) compared with the other groups of histologic subtype (0%). The results suggest positivity in nucleus staining for p53 may be a marker for the biologically worse carcinomas, PDC and UDC, however, tumors showing only cytoplasmic staining of p53 favor a fair prognosis. In this paper, we also elucidate the spectrum of genotypic aberrations of p53 in each histological subtype. Of 92 thyroid tumor samples analyzed, the overall frequency of p53 mutation was 8.5%. The mutations occurred in 4.35% (2/46) ot WDC, 17.2% (5/29) of PDC, and 16.7% (1/6) of oncocytic carcinoma. Two of five PDC cases and one papillary carcinoma revealed point mutations in exon 8 as follows; GTG (val) to CTG (leu) at codon 272 in case 23T, CGA (arg) to CCA (pro) at codon 306 in case of 30T, and CGG (arg) to AGG (arg) at codon 282 in case 28T. All of the p53 mutations detected were represented by single nucleotide changes including two missense and one silent mutation. In contrast to the missense mutations found in PDC, it is interesting to note that the silent mutation was checked in 28T of well differentiated papillary carcinoma. These results represents molecular evidence that p53 gene aberration associated with overexpression of the mutant form of p53 protein plays a crucial role in the biologically aggressive subtypes of thyroid carcinoma, and point mutation only was not sufficient to be a prognostic marker for the biologically aggressive malignancy of thyroid tumors. There was no p53 gene aberration found in four cases of undifferentiated carcinoma (UDC) studied. The results suggest that other unknown factors should be responsible for the aggressiveness in some UDC of thyroid carcinoma except overexpression of p53.

Carcinoma↗

PubMed1996

p53 mutations in gastric cancers from Taiwan.

Mutations of the p53 gene were investigated in 80 surgical specimens of primary gastric cancer by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations were detected in 18 tumors (22.5%) and localized to exons 5, 7 and 8. Mutations did not follow a random distribution among different subtypes, but instead clustered in the group of papillary adenocarcinomas, in which 7/12 (58.3%) cases were mutated. Positivity for p53 mutation was significantly higher in intestinal-type (37.5%) than in diffuse-type carcinomas (12.5%). These results suggest that gene alterations of p53 are not rare and may participate in the carcinogenesis of intestinal-type carcinomas of the stomach. Twenty of 21 p53 mutations were represented by single nucleotide changes, mostly missense mutations (19 events) and one nonsense mutation. Transversional mutations constitute the majority of p53 mutations (65%) and only 20% of mutations show G:C to A:T transitions. It is possible that the etiologies of gastric cancer in different geographical areas are different.

Adult↗

PubMed1995

Loss of heterozygosity of APC/MCC gene in differentiated and undifferentiated gastric carcinomas in Taiwan.

Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and also shown to be associated with the development of esophageal and lung cancers. To determine if these genes are also involved in the development of gastric cancer, 79 primary human gastric cancers were examined for loss of heterozygosity of APC or MCC or both. Loss of APC was detected in 20% of 15 informative differentiated cases, but not in 20 informative undifferentiated cases, while loss of MCC occurred in 23.5% of 17 informative undifferentiated cases, but not in 19 informative differentiated cases. These data suggest that loss of heterozygosity of APC/MCC gene is involved in the development of gastric carcinomas, and that distinctly different molecular mechanism(s) may be responsible for the development of differentiated and undifferentiated gastric carcinomas.

Base Sequence↗

PubMed1995

Absence of p53 gene mutation and infrequent overexpression of p53 protein in hepatoblastoma.

Ten cases of hepatoblastoma were studied for overexpression of p53 protein by immunohistochemistry and for possible p53 gene mutation by single strand conformation polymorphism (SSCP) analysis and direct DNA sequencing of the polymerase chain reaction products. Only one case of the macrotrabecular type at stage IV showed overexpression of p53 protein. No DNA mobility shift was found in any of these cases studied by SSCP analysis. DNA sequencing performed on the case showing overexpression of p53 protein revealed no mutation within exons 5 to 8. The associated adrenal cortical carcinoma of the same case also showed overexpression of p53 protein, but no mutation of the p53 gene. These results indicate that mutation of the p53 gene is infrequent in hepatoblastoma. This observation supports the view that mutation of the p53 gene is not as important in the oncogenesis of childhood neoplasms as in adult cancers.

Base Sequence↗

PubMed1994

Arsenic-related Bowen's disease and paraquat-related skin cancerous lesions show no detectable ras and p53 gene alterations.

We have investigated point mutations of codons 12, 13, and 61 in H-, K-, and N-ras oncogenes as well as p53 tumour suppressor gene exon 5 through exon 9 by PCR-SSCP analysis in 26 skin biopsy tissues from 16 arsenic-related Bowen's disease patients and 6 skin samples from 4 paraquat manufacturing workers. No mutation was found. These results are different from findings with UV associated skin cancers. Interestingly, a silent change at codon 27 of H-ras in one allele was detected in all 4 paraquat manufacturing workers and in 2 of 16 arsenic-related Bowen's disease patients. It is likely that the molecular mechanisms involved in arsenic and paraquat induced skin cancers differ from sunlight-related skin malignancies.

Arsenic↗

PubMed1994

p53 gene mutations in brain tumors in Taiwan.

Mutations of the p53 gene were investigated in 116 surgically removed primary brain tumor tissues by PCR-SSCP analysis. The mutations did not follow a random distribution among the various different subtypes, but occurred in 21.0% (13/62) of astrocytomas, 13.0% (3/23) of oligodendrogliomas and 35% (7/20) 35% (7/20) of PNETs. No mutation was found in the ependymomas. The majority of mutations identified in this study were G:C to A:T or C:G to T:A transitions (56.0%, 14 of 25) and occurred most frequently (56.0%, 14 of 25) at sites of CpG dinucleotides. Interestingly, codon 158 is a new hot spot which occurred with a frequency of 16.0% (4 of 25) in the samples analyzed.

Base Sequence↗

PubMed1994

Ethnic variation in the CYP2E1 gene: polymorphism analysis of 695 African-Americans, European-Americans and Taiwanese.

Human cytochrome P4502E1 (CYP2E1) is inducible by ethanol and is involved in metabolism of many known carcinogens including N-nitrosodimethylamine, butadiene, benzene, and carbon tetrachloride. A 50-fold variability in CYP2E1 enzyme activity in humans has been observed but it is unknown whether the basis for this variation is genetic or environmental. Recently, two restriction fragment length polymorphisms (RFLPs) within the CYP2E1 gene have been suggested as genetic markers of risk for cancer. The first was a Rsa I polymorphism in the 5' regulatory region that appeared to alter transcriptional activation of the gene and the second was a Dra I polymorphism located approximately 7000 bp downstream in an intron. Rare alleles at each of these loci have been associated with a reduced risk for lung cancer in Japanese and Swedish populations. We have used a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to determine the genotype frequency for each of these CYP2E1 RFLPs in 695 individuals of Taiwanese, African-American or European-American background. Genotype and allele frequencies for Taiwanese were significantly different from those of African-Americans and European-Americans at either Rsa I or Dra I sites (p < 0.0001). Allele frequencies for African-Americans and European-Americans were significantly different at the Rsa I site (p = 0.03). The rare alleles (c2 and C) occurred at frequencies of 0.28 and 0.24 in Taiwanese, 0.01 and 0.08 in African-Americans, and 0.04 and 0.11 in European-Americans. In addition, we describe three haplotypes common to all three population samples and a fourth haplotype that was only detected in the Taiwanese population sample. This fourth haplotype may have been caused by a recombination event between these markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Asian People↗