Shih-Meng Tsai

Mortality for Certain Diseases in Areas with High Levels of Arsenic in Drinking Water

Blackfoot disease was prevalent in a limited area on the southwest coast of Taiwan, where artesian well water containing arsenic (median = 0.78 ppm arsenic) had been used for many years. Previous studies of arsenic exposure in the blackfoot disease endemic area have been focused on malignant tumors. We, therefore, conducted this study to analyze mortality of all death causes in blackfoot disease endemic areas and to determine other neglected cancers or noncancer diseases related to artesian well water containing high levels of arsenic. We calculated standardized mortality ratios for cancer and noncancer diseases, by sex, during the period from 1971 to 1994 and compared them to the local reference group (i.e, Chiayi-Tainan County) and the national reference group (i.e., Taiwan population). The results revealed marked standardized mortality ratio differences for the 2 reference groups. Greater mortality was found for males and females with bladder, kidney, skin, lung, nasal-cavity, bone, liver, larynx, colon, and stomach cancers, as well as lymphoma than in the local reference population. With respect to noncancer diseases, we found greater mortality for males and females who had vascular disease, ischemic heart disease, diabetes mellitus, and bronchitis than in the local reference group. Mortalities for other diseases--including rectal cancer, cerebrovascular disease, and other diseases--were higher among cases than the local reference group. Our results indicated that the hazardous effect of arsenic is systemic. Diseases related to arsenic exposure included those reported previously by other investigators, as well as diseases reported in the present study.

Different impact from betel quid, alcohol and cigarette: risk factors for pharyngeal and laryngeal cancer.

The risks of betel quid chewing with or without tobacco, alcohol drinking and cigarette smoking have been well explored in the oral cavity but not in the pharynx and larynx. We conducted a case‐control study to investigate the association of these three risk factors to cancers of the pharynx and larynx in Taiwan. A total cases of 148 pharyngeal cancer, 128 laryngeal cancer and 255 hospital controls, all men, were recruited. Betel quid chewing was a significant independent risk factor (adjusted odds ratio [aOR] = 7.7; 95% confidence interval [CI] = 4.1–15.0) similar to that of alcohol drinking (aOR = 6.6; 95% CI = 3.5–13.0) for pharyngeal cancer, but not for laryngeal cancer (aOR = 1.3; 95% CI = 0.7–2.5) on which cigarette smoking (aOR = 7.1) exerts a stronger significant independent risk than alcohol drinking (aOR = 3.8). For pharyngeal cancers, chewers who consumed >20 quid/day, chewed with inflorescence in the quid or swallowed the betel quid juice were at higher risks; significant dose‐response effects were found in daily quantity of drinking and chewing, and cumulative quantity of drinking. Synergistic effects from the 3 risk factors existed both on the pharynx (aOR = 96.9) and the larynx (aOR = 40.3), and attributed for 93.1% and 92.9% respectively. Our study is the first evidence to show that betel quid chewing without tobacco has different impact on the pharynx (digestive tract) and the larynx (airway), and supports the concept that exposure quantity and direct mucosal contact with the betel quid juice may contribute to carcinogenesis. Our results show an important insight into the impact of betel quid chewing on other sites of the digestive tract other than the oral cavity.

Interaction between cigarette, alcohol and betel nut use on esophageal cancer risk in Taiwan

Objective  In 2003 esophageal cancer was the sixth leading cause of death among men in Taiwan, but it is the fastest increasing (70%) alimentary tract cancer. The aim of this study was to investigate the impact of different habits of betel nut chewing on esophageal squamous cell carcinoma (SCC) and its interaction with cigarette use and alcohol consumption.

Cancer mortality trends in a blackfoot disease endemic community of Taiwan following water source replacement.

Blackfoot disease is an endemic peripheral vascular disease found among people in a limited area on the southwest coast of Taiwan, where artesian well water has a high concentration of arsenic and was used since the turn of this century. This is an important public health problem and was noted by the authorities, who began improving the water supply in such communities in 1956. This enabled us to test the relationship between arsenic and malignant tumors using a specific exposed community. Study subjects were divided into four groups according to age (under or over 40 yr) and gender. Two methods were used for the estimation of the age-adjusted mortality rate ratios. First using the first time interval (1971-1973) as the standard, the mortality rate ratio for all malignant tumors was estimated from this interval through to the last interval (1992-1994) using Poisson regression. Cancers that were found to be related to arsenic in previous reports, such as liver, lung, bladder, kidney, and skin cancers, were examined and other malignant tumors except these cancers were also assessed. The same calculations were performed for all of Chiayi and Tainan counties, excluding the study areas, which were used as the local reference, and for the general population of Taiwan, which was used as a national reference group. Second, mortality rate ratios for the study area were compared to the local and national reference for the same time intervals for each disease category. From our results, significantly declining trends for mortality rate ratios of all malignant tumors with 1971-1973 as the standard were found for the study areas, especially in females. A decrease of mortality rate ratios from malignant cancers, compared to the local or national references, was found in those aged over 40 yr for both sexes. The decreases are mainly due to a fall in internal and skin cancer mortality rates. In conclusion, our results suggest that the improvement of drinking water supply to eliminate arsenic exposure from artesian well water decreased the mortality incidence of arsenic-related cancers in blackfoot disease endemic communities.

Changes of lipid peroxide levels in blood and liver tissue of patients with obstructive jaundice

Plasma lipid peroxide levels, hereafter referred to as PLP levels, were measured in a group of 40 apparently healthy controls and 64 cholelithiasis patients, 40 with and 24 without jaundice. Hepatic lipid peroxide (HLP) levels were also measured in 26 patients, 15 with and 11 without jaundice. There was a significantly higher mean concentration of PLP in the jaundiced patients than in the control or jaundice-free cases. However, the difference in PLP levels between the jaundice-free and the control cases was insignificant. Meanwhile, patients with jaundice had significantly higher HLP levels than those without jaundice. In the jaundiced cases, the increased PLP and HLP levels were clearly related to the serum levels of bilirubin respectively. In addition, the HLP levels were positively correlated with the PLP levels; however, in the non-jaundiced cases, there was little evidence of these two relationships. Patients with or without jaundice had lower plasma vitamin E levels in comparison to the control cases. The correlation of plasma vitamin E and PLP levels was weak in all of the jaundiced. However, when we subdivided the jaundiced into two groups, the correlation was strong in those with plasma vitamin E levels < 8.5 micrograms/ml, while the correlation was weak in those with plasma vitamin E levels > 8.5 micrograms/ml. Consequently, these results suggest that there is an involvement of lipid peroxidation in liver cells damaged by obstructive jaundice in cholelithiasis patients and there exists a negative correlation between low vitamin E and lipid peroxide levels in plasma.

Side effects after docetaxel treatment in Taiwanese breast cancer patients with CYP3A4, CYP3A5, and ABCB1 gene polymorphisms

BACKGROUND Breast cancer patients initiating TEC (including docetaxel, epirubicin, and cyclophosphamide) treatment were genotyped for CYP3A4, CYP3A5, and ABCB1 to identify variability factors of side effects for docetaxel. METHODS The planned dose of docetaxel per course was formulated according to each patients height and weight. Each participant had received TEC treatment for 6 consecutive cycles. The single nucleotide polymorphisms (SNPs) of CYP3A4*4 (352A > G), CYP3A4*5 (653C > G), and CYP3A4*18A (20070T > C) for the CYP3A4 gene, CYP3A5*3A (6986A > G) for the CYP3A5 gene, and -41A > G, -145C > G, 1236C > T, 2677G > T(A), and 3435C > T SNPs for the ABCB1 gene were determined by using the restriction fragment length polymorphism of polymerase chain reaction products and the restriction enzymes. RESULTS Fifty-nine Taiwanese women (mean age, 46 y; range, 30-64 y) treated for breast cancer with TEC were recruited. We found that patients carrying the CYP3A5*1/*3 genotype demonstrated more side effects of fever, pleural effusion, and febrile neutropenia than those with the CYP3A5*3/*3 genotype (p = 0.075, 0.077, and 0.030, respectively); moreover, patients with the ABCB1 2677G/G genotype also showed more side effects of fever and febrile neutropenia than those with other genotypes (p = 0.024 and 0.027), In regard to ABCB1 3435C>T, patients with ABCB1 3435C/C tended to suffer leucopenia (p = 0.057). CONCLUSIONS There could be correlations between certain side effects of docetaxel treatment and polymorphisms of these metabolic enzymes. Unfortunately, there is not so much evidence due to the small sample size of this study which restricts the statistical power.

The neoplastic impact of tobacco-free betel-quid on the histological type and the anatomical site of aerodigestive tract cancers

Little is known about any consequences of swallowing tobacco‐free betel‐quid (TF‐BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to gastrointestinal tract (GIT). We investigated the neoplastic impact of TF‐BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case–control study examining patients with 2,163 pathology‐proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose‐dependent structures and cancer risks. Contrary to nonsignificant GIT‐adenocarcinoma risk (aOR = 0.9), TF‐BQ users experienced a 1.7‐ to 16.2‐fold higher risk of UADT‐squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF‐BQ dose‐risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first‐piecewise increased risk of esophageal cancer was recognized among areca‐fluid swallowers than among nonswallowers (continuous aOR = 1.12 vs. 1.03). TF‐BQ use accounted for 66.1–78.7% and 17.8–33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF‐BQ consumption to low‐to‐moderate consumption only reduced 11.3–34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra‐additively modified the risk of TF‐BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF‐BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.

The association between lipid profiles and breast cancer among Taiwanese women.

Abstract Background: Breast cancer incidence increased seven-fold from 1979 to 2002, and it has become the second most common cancer in Taiwanese women. Although the relationship between high-density lipoprotein cholesterol (HDL-C) and breast cancer has been studied, no consistent association has been explicitly confirmed. The aim of this study was to demonstrate the relationship between breast cancer and lipid profiles in Taiwanese women. Methods: A total of 150 breast cancer patients before treatment and 71 healthy controls were enrolled. Lipid profiles in fasting serum were measured after participants gave their consent. Results: The breast cancer patients had significantly lower values for HDL-C and apolipoprotein A-I (apoA-I), lower apoA-I/apoB ratios and higher values for very-low-density lipoprotein cholesterol (VLDL-C) than controls. After logistic regression analysis, the breast cancer patients had significantly higher values for VLDL-C and lower values for apoA-I after controlling for HDL-C and the apoA-I/apoB ratio. Conclusions: Our findings demonstrate that higher VLDL-C and lower apoA-I values were significantly associated with breast cancer, with a greater association between apoA-I values and the development of breast cancer than for HDL-C values. Clin Chem Lab Med 2007;45:1219–23.

Evaluation of redox statuses in patients with hepatitis B virus-associated hepatocellular carcinoma.

Background Excess reactive oxygen species related to neoplasia of liver has been established. Essentially, the human body has developed different antioxidant systems for defence against these attacks. To evaluate the redox status in hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV), the most important aetiological factor in Taiwan, changes in O2 . generation, lipid peroxidation as well as antioxidant status in the blood of HCC patients with HBV carriers for more than 20 years were measured. Methods Superoxide anion radical (O2 .−) generation and the levels of malondialdehyde (MDA) served as an index of lipid peroxidation along with the analyses of activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx); also, glutathione status, including reduced glutathione (GSH) and oxidized glutathione (GSSG), and the levels of vitamins A, C and E were determined. Results In 54 patients, the levels of O2 .−, MDA and GSSG, and the activities of SOD and GRx of blood were significantly higher than those of 57 controls. Conversely, the levels of GSH and total GSH, and GSH/GSSG ratio, and vitamins A and C were significantly decreased. Additionally, there were no significant changes in the activity of GPx and the levels of vitamin E. Conclusions Our data suggest that the redox statuses in patients with HBV-associated HCC were elevated or decreased in certain parameters. However, the increased activities of antioxidant enzymes may be a compensatory up-regulation and the decrease antioxidant statuses were responses to the enhanced oxidative stress in those patients.

The clinical significance between activation of nuclear factor kappa B transcription factor and overexpression of HER-2/neu oncoprotein in Taiwanese patients with breast cancer.

BACKGROUND This study investigated the role of nuclear factor-kappa B (NF-kappaB) activity in human breast cancer with overexpression of HER-2/neu oncoprotein, as well as its role on expression of different histological grades of cancer cells taken from Taiwanese breast cancer patients. MATERIALS AND METHODS Specimens were collected from 82 female breast cancer patients. The HER-2/neu oncoprotein was measured by immunohistochemistry. NF-kappaB activity expression was assessed by the electrophoretic mobility shift assay, and confirmed by the supershift technique using anti-P65 antibody in both breast cancer tissue and the adjacent normal tissue. The histological grades were measured by Modified Bloom-Richardson Grading Scheme. RESULTS Of the 82 cancer specimens, 81 (98.7%) showed higher or equal expressions of NF-kappaB activity when compared to the adjacent normal tissue. Fifty-five cases (67.1%) had higher levels of NF-kappaB activity in the cancerous tissue than in the adjacent normal tissue (p<0.005). With regard to tumor size, steroid receptors, stages, histological types, and node status, there were no statistically significant differences in NF-kappaB activity between cancerous tissues and adjacent normal tissues. However, significantly higher expressions of NF-kappaB activity were seen in those cases with positive HER2/neu oncoprotein, poorly differentiated histological grades, high nuclear pleomorphisms, and high mitotic counts (p<0.05). Positive HER-2/neu overexpression of oncoprotein had higher NF-kappaB activity (86%) than negative overexpression (60%) (p<0.05). It has been shown that the NF-kappaB activity increases in the HER-2/neu oncoprotein overexpression in human breast cancer. CONCLUSION Overexpression of HER-2/neu gene could induce NF-kappaB activity in human breast cancer cells, as has been confirmed in other research on cell lines.