Meng-Hsuan Cheng

Outdoor air pollution and female lung cancer in Taiwan.

To investigate the relationship between air pollution and female lung cancer, the authors conducted a matched case-control study using female deaths that occurred in Taiwan from 1994 through 2003. Data on all eligible female lung cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of women who died from causes other than cancer or diseases associated with respiratory problems. The controls were pair matched to the cases by sex, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. A municipality-based aggregate index of long-term exposure to air pollution was created by dividing the annual average of the measured values for each pollutant by the National Ambient Air Quality Standard for that pollutant. The ratios for each pollutant were scaled to a 100-point scale and then averaged together to generate an index value representing the net burden of these pollutants, with each weighted equally. The subjects were divided into tertiles according to the levels of the index just described. Women who lived in the group of municipalities with highest levels of air pollution exposure index were at a statistically significant increased lung cancer risk compared to the group living in municipalities with the lowest air pollution exposure index after controlling for possible confounders (OR = 1.28, 95% CI = 1.02–1.61). The findings of this study warrant further investigation of the role of air pollutants in the etiology of lung cancer.

Air pollution and hospital admissions for pneumonia in a subtropical city: Taipei, Taiwan.

This study was undertaken to determine whether there was an association between air pollutant levels and hospital admissions for pneumonia in Taipei, Taiwan. Hospital admissions for pneumonia and ambient air pollution data for Taipei were obtained for the period from 1996–2004. The relative risk of hospital admission was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single pollutant models, on warm days (>23°C) statistically significant positive associations were found in all pollutants. On cool days (<23°C), all pollutants were significantly associated with pneumonia admissions except SO2. For the two-pollutant model, O3 and NO2 were significant in combination with each of the other 4 pollutants on warm days. On cool days, PM1 0, CO, and O3 remained statistically significant in all the two-pollutant models. This study provides evidence that higher levels of ambient air pollutants increase the risk of hospital admissions for pneumonia.

Air Pollution and Hospital Admissions for Asthma in a Tropical City: Kaohsiung, Taiwan

This study was undertaken to determine whether there is an association between air pollutants levels and hospital admissions for asthma in Kaohsiung, Taiwan. Hospital admissions for asthma and ambient air pollution data for Kaohsiung were obtained for the period from 1996 through 2003. The relative risk of hospital admission was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (≥ 25°C) statistically significant positive associations were found in all pollutants except sulfur dioxide (SO2). On cool days (≤ 25°C) all pollutants were significantly associated with asthma admissions For the two pollutant models, CO and O3 were significant in combination with each of the other four pollutants on warm days. On cool days NO2 remained statistically significant in all the two-pollutant models. This study provides evidence that higher levels of ambient pollutants increase the risk of hospital admissions for asthma.

Statin use and the risk of female lung cancer: a population-based case-control study.

The aim of this study was to investigate whether the use of statins was associated with lung cancer risk. We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases consisted of all female patients who were aged 50 years and older and had a first-time diagnosis of lung cancer for the period between 2005 and 2008. We identified four control patients per case patient. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. We examined 297 female lung cancer cases and 1188 controls. The unadjusted odds ratios (ORs) for any statin prescription were 0.78 (95% confidence interval=0.57-1.07) and the adjusted OR was 0.82 (95% CI=0.58-1.15). Compared with no use of statins, the adjusted ORs were 0.83 (95% CI=0.54-1.28) for the group having been prescribed statins with cumulative defined daily dose (DDDs) below 92.41 and 0.79 (95% CI=0.50-1.25) for the group with cumulative statin use of 92.41 DDDs or more. The present data do not provide support for a beneficial association between statin use and female lung cancer risk.

Statin use and the risk of colorectal cancer: A population-based case-control study

AIM To investigate whether the use of statins is associated with colorectal cancer risk. METHODS We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National Health Insurance Research Database. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of colorectal cancer between the period 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS We examined 1156 colorectal cancer cases and 4624 controls. The unadjusted ORs for any statin prescription was 1.10 (95% CI = 0.94-1.30) and the adjusted OR was 1.09 (95% CI = 0.91-1.30). When statin use was categorized by cumulative dose, the adjusted ORs were 0.99 (95% CI = 0.78-1.27) for the group with cumulative statin use below 105 defined daily doses (DDDs); 1.07 (95% CI = 0.78-1.49) for the group with cumulative statin use between 106 and 298.66 DDDs; and 1.30 (95% CI = 0.96-1.75) for the group with cumulative statin use of 298.66 DDDs or more compared with nonusers. CONCLUSION This study does not provide support for a protective effect of statins against colorectal cancer.

B1, a novel topoisomerase II inhibitor, induces apoptosis and cell cycle G1 arrest in lung adenocarcinoma A549 cells.

In our previous studies, we demonstrated that 2,6-bis-(2-chloroacetamido) anthraquinone (B1) showed a highly significant cytotoxic effect. However, its influence in the cell cycle and apoptotic induction effects has not been investigated yet. Here we report the antiproliferative effect of B1, for which IC50 values were 0.57 &mgr;mol/l for lung cancer A549 cells, 0.63 &mgr;mol/l for colon cancer HT-29 cells, and 0.53 &mgr;mol/l for breast cancer MCF-7 cells. DNA topoisomerase II (Topo II), an essential enzyme in DNA synthesis and meiotic division, is highly expressed in cancer cells. Some currently used clinical anticancer drugs (doxorubicin and mitoxantrone) targeting Topo II are very effective antineoplastic agents. B1, sharing the basic structure of known Topo II inhibitors, demonstrated a significant inhibitory effect on Topo II bioactivity. In A549 cells, B1 increased apoptotic cell population with induction of Fas, Bax, and cleaved poly(ADP-ribose) polymerase and by reduction of Bcl-2 expression. Moreover, cell cycle analysis indicated that B1 induced G1 phase arrest through modulation of G1 cell cycle regulatory proteins, such as the downregulation of cyclin D1 and upregulation of Cip/p21, Kip1/p27, and p53. Thus, our study suggests that B1, with the ability to inhibit Topo II activity and cause cell cycle G1 arrest and apoptosis, has potential as a novel anticancer agent.

Parity and Risk of Death From Lung Cancer Among a Cohort of Premenopausal Parous Women in Taiwan

Background We examined the association between parity and risk of lung cancer. Methods The study cohort consisted of all women with a record of a first singleton birth in the Taiwanese Birth Register between 1978 and 1987. We tracked each woman from the time of their first childbirth to 31 December 2009. Follow-up was terminated when the mother died, when she reached age 50 years, or on 31 December 2009, whichever occurred first. The vital status of mothers was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for death from lung cancer associated with parity. Results There were 1375 lung cancer deaths during 32 243 637.08 person-years of follow-up. The mortality rate of lung cancer was 4.26 cases per 100 000 person-years. As compared with women who had given birth to only 1 child, the adjusted HR was 1.13 (95% CI, 0.94–1.35) for women who had 2 children, 1.10 (0.91–1.33) for those who had 3 children, and 1.22 (0.96–1.54) for those who had 4 or more children. Conclusions The findings suggest that premenopausal women of higher parity tended to have an increased risk of lung cancer, although the trend was not statistically significant.

B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB

We previously demonstrated that B1 induced significant cytotoxic effects, cell cycle G1 arrest and apoptosis in human lung cancer A549 cells through the inhibition of DNA topoisomerase II activity. In the present study, we focused on the histone deacetylase (HDAC) modulation of B1 in A549 cells. HDACs, important enzymes affecting epigenetic regulation, play a crucial role in human carcinogenesis. Our findings showed that B1 could suppress the growth of A549 cells in vitro through the inhibition of HDAC activity. Additionally, B1 caused disruption of the mitochondrial membrane potential and induced DNA double-strand breaks (DSBs) in a dose- and time-dependent manner, which consequently led to cell apoptosis. We also observed that B1 inhibited cancer cell migration and angiogenesis-related signal expression, including vascular endothelial growth factor (VEGF) and pro-matrix metalloproteinases-2 and -9 (pro-MMP-2/9). Gelatin zymography suggested that B1 decreased pro-MMP-2 and pro-MMP-9 activity. Transcription factors, signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB), are vital players in the many steps of carcinogenesis. B1 showed significant dose-response inhibitory effects on cytoplasmic expression and nuclear translocation of both phosphorylated STAT3 (pSTAT3) and NF-κB. It has been well documented that reactivated telomerase confers cancer cells the ability to repair DNA. Real-time PCR results indicated that B1 inhibited STAT3 and NF-κB mRNA expression and telomerase activity. Taken together, our results demonstrated that B1 exerted significant inhibitory effects on HDAC, telomerase activities, oncogenic STAT3 and NF-κB expression. The inhibition of the intricate crosstalk between STAT3 and NF-κB may be a major factor in the molecular action mechanism of B1. The multiple targeting effects of B1 render it a potential new drug for lung cancer therapy.