◆ Major Achievements and Contributions
Dr Pau-Chung Chen is Distinguished Professor of the Institute of Environmental and Occupational Health Sciences at the National Taiwan University College of Public Health and Director of the Office of Occupational Safety and Health at the National Taiwan University Hospital. He has conducted research on environmental and occupational exposures on fertility, fetuses, infants and children based on cohort studies. He is also interested in cancer causes and prevention by using health informatics research. Dr Chen has published more than 300 scientific articles and received the Distinguished Research Award from the Ministry of Science and Technology in 2015. He served as chair of the Scientific Committee on Reproductive Hazards in the Workplace (RHICOH), International Commission on Occupational Health (ICOH) in 2012-2018 and was the first chair of the Birth Cohort Consortium of Asia (BiCCA) in 2012-2014. Currently, he serves as President of the Taiwan Public Health Association. Finally, Dr Chen has also been invited to be the plenary speakers or scientific committee members in international conferences or symposia, special lectures in Asian universities, and guest editors and academic reviewers in well-known international journals.
- Reproductive Hazards in the Workplace and Environment
Silent Spring by Rachel Carson in 1962 was an eloquent and urgent warning about the dangers of the natural world contaminated by manmade pesticides. Our Stolen Future by Colborn et al in 1996 provided a vivid account of emerging scientific research about how a wide range of manmade chemicals disrupt delicate hormone systems, which play a critical role in processes ranging from human sexual development to behavior, intelligence, and the functioning of the immune system. Occupational or environmental exposures to heavy metals, organic solvents, persistent organic pollutants, pesticides, endocrine disrupting chemicals, and radiation could injure our reproduction and offspring and became important public health issues. Dr Pau-Chung Chen has been working in the research filed of reproductive and developmental epidemiology in recent decades and conducted several occupational or environmental cohort studies including lead-acid battery, semiconductor industry, and electronics worker cohorts, and a prospective pregnancy cohort in Taipei. Our team has achieved the continuing and unique contribution in this field and played a leading role in Asia as well as in the world. Dr Chen is honored to be a member of the executive board of the Scientific Committee on Reproductive Hazards in the Workplace, International Commission on Occupational Health since 2007 and was the chair of the committee in 2012-2018. We held the first International Symposium of Reproductive Hazards in the Workplace and Environment (RHICOH) in Taipei on April 20-21, 2010, the second symposium in Utrecht, The Netherlands on June 18-19, 2013, the third symposium in Barcelona, Spain on September 5-6, 2016, and the fourth symposium in Taipei, Taiwan on June 23-24, 2018.
- Children’s Environmental Health Based on Birth Cohort Studies
We started to conduct a longitudinal birth cohort follow-up study to investigate the environment, genetics, and children’s health issues in recent years. Children’s environmental health is increasingly recognized as a global public health issue of great importance. Given our current limited knowledge, the distribution of environmental contaminant exposure levels among reproductive-age, infants, and children is unknown; and the role of prenatal and postnatal exposures to environmental and genetic factors in the etiology of adverse child health is unsolved. The current problems in Taiwan we have identified to perform researches including: the prevalence of asthma is still increasing up to more than 10%; preterm delivery has been increasing up to 9% in 2003; neurodevelopmental disorders are highly prevalent and affected 8% of the examined children under the age of four years; and the prevalence of childhood obesity has doubled. Therefore, we started to conduct a project “Taiwan Birth Panel Study” to investigate prenatal and postnatal factors on infant and early childhood health. Through this prospective birth cohort, the main health outcomes focused on atopic diseases, child growth and development, and neurocognitive and language development. We investigated the main prenatal and postnatal factors including infection, herb use in pregnancy, breastfeeding, allergens and other pollutants such as environmental tobacco smoke, heavy metals, non-persistent pesticides, melamine, perfluoroalkyl substances (PFASs), phthalates, bisphenol-A, acrylamides, and psychosocial stress under the consideration of interaction of the environment and genes. Among them, our research team has been working on PFASs and children’s health since 2009 and we found that exposure to PFASs was related to reduced fetal growth, delayed children’s neurodevelopment, increasing IgE levels, increasing risk of childhood asthma and severity, disturbed thyroid and reproductive hormones, and increasing carotid artery intima-media thickness. We have published 30 related articles in international journals and have now become a leading research team to study the human health effects of perfluoroalkyl substances in the world. The list of related publications you can find on our website. Recently, we first reported that household incense burning exposure was associated with delay in gross motor neurodevelopmental milestones (Environ Int 2018). This project bridges knowledge gaps and answer unsolved issues in the low-level, prenatal or postnatal, and multiple exposures, genetic effect modification, and the initiation and progression of “environmentally-related childhood diseases.” In addition, we play an active role in education, research, and services in the field of “pediatric environmental health” via integrating multi-disciplines. To provide clinical service, exposure assessment, and risk communication, we set up the Environmental Medicine Coordination Center at the National Taiwan University Hospital since 2014, annually held the International Symposium of Environmental Medicine, and recently published a book “Understanding Toxics in Your Daily Life (毒懂您的生活)” for the general public.
- Birth Cohort Consortium of Asia (BiCCA)
The Millennium Developmental Goals (MDGs), which are derived from the United Nations Millennium Declaration, has rising the importance of child health and environmental sustainability in 2000. According to World Health Organization (WHO)’s survey, over 40% of the global burden of disease attributed to environmental factors falls on children below five years of age who account for only about 10% of the world’s population. The environmental health of children is one of the great global health concerns. What a developing child is exposed to in utero and in his/her early years has major consequences on later health. However, environmental risks or disease burdens vary from region to region. Birth cohort studies are ideal for investigating different environmental risks. The principal investigators of three birth cohorts in Asia including the Taiwan Birth Panel Study (TBPS), the Mothers and Children’s Environmental Health Study (MOCEH), and the Hokkaido Study on Environment and Children’s Health (Hokkaido Study) co-established the BiCCA. We held the first meeting for the Birth Cohort Consortium of Asia (BiCCA) to investigate the environment, genetics, and children’s health issues in Asia and Dr Pau-Chung Chen was elected as one of the executive committee members and the first chair in 2012-2014. To date, 31 birth cohorts have been established in 16 Asian countries, consisting of approximately 80,000 study subjects in the BiCCA. Our introduction article provides the study framework, environmental exposure and health outcome assessments, as well as maternal and infant characteristics of the participating cohorts (Epidemiology 2017). The BiCCA provides a unique and reliable source of birth cohort information in Asian countries. Further scientific cooperation is ongoing to identify specific regional environmental threats and improve the health of children in Asia (Sci Total Environ 2017; Environ Res 2019). Please see our website for further information.
- Preventive Actions of Banning Herbal Medicine Containing Aristolochic Acid
The consumption of Chinese herbs containing aristolochic acid has been associated with an increased risk of urothelial carcinoma. The International Agency for Research on Cancer listed that plants containing aristolochic acid are carcinogenic to humans (Group 1) in 2002 and that aristolochic acid is carcinogenic to humans (Group 1) in 2012. We conducted a series of studies of Chinese herbs containing aristolochic acid and reported increased risks of chronic kidney disease, kidney failure and urinary tract cancers in Taiwan. In addition, increased risk of kidney failure and urinary tract cancers were also found among Chinese herbalists. Further, Chen et al. investigated 152 patients with upper urinary tract urothelial carcinoma and found the 93 had been exposed to aristolochic acid based on the presence of aristolactam-DNA adducts and AA-mutational signature in the renal cortex. Finally, aristolactam-DNA adducts were also detected in 76% of clear cell renal cell carcinoma (ccRCC) and AA-mutational signature was evident in 6 of 10 sequenced ccRCC exomes from Taiwanese patients. Due to our early studies, we convinced our government to take preventive actions of banning Chinese herbs containing aristolochic acid. Recently, we first found that a significant linear dose-response relationship between aristolochic acid consumption and hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients. This suggests that aristolochic acid, which may be associated with HBV infection, plays an important role in HCC pathogenesis, and HBV and HCV patients who took those herbs should be followed up (Int J Cancer 2018; Cancer Epidemiol Biomarkers Prev 2019).
- Cancer Chemoprevention Based on Health Informatics Research
An ounce of prevention is better than a pound of cure. Cancer risk reduction using pharmacological means is an attractive modern preventive approach that supplements the classical prevention or treatment recommendations. Statins have potential protective effects against cancers, but no studies have focused on patients with chronic hepatitis B or C virus (HBV or HCV) infection. The purpose of this study was to investigate the association between the use of statins in HBV- or HCV-infected patients and the risk of hepatocellular carcinoma (HCC). We conducted a population-based cohort study from the Taiwan National Health Insurance Research Database. Statin use may reduce the risk for HCC in HBV- or HCV-infected patients in a dose-dependent manner. These findings have also been replicated in Denmark (N Engl J Med 2012), Sweden (Pharmacoepidemiol Drug Saf 2014; Ann Intern Med 2019), United States (Cancer Epidemiol 2014; Hepatology 2015; Clin Gastroenterol Hepatol 2019; J Clin Gastroenterol 2020), United Kingdom (JNCI 2015; Int J Cancer 2020), Hong-Kong (J Hepatol 2015), and Korea (J Hepatol 2017; Hepatology 2020) since then and cited by UpToDate. We published two original articles on Journal of Clinical Oncology, which have been listed as “Highly Cited Paper and Research Front Core Paper” by ISI Essential Science Indicators. We also reported that statin use was associated with a reduced risk of cirrhosis development in a dose-dependent manner among the patients with HCV infection (J Hepatol 2015). Another cancer chemopreventive agent acarbose, an alpha-glucosidase inhibitor, has been shown to reduce the risk of incident colorectal cancer in patients with diabetes in a dose-dependent manner (Diabetes Care 2015).
- Expert Witnesses for the RCA Corporation Employees Caring Association
In 1994, a hazardous waste site, polluted by the dumping of solvents from a former electronics factory, was discovered in Taoyuan, Taiwan. This subsequently emerged as a serious case of contamination through chlorinated hydrocarbons with suspected occupational cancer. We found that female workers with exposure to trichloroethylene (TCE) and/or mixture of solvents may have an excess risk of breast cancer. Female workers with potential exposure to organic solvents during periconception might increase risks of childhood cancers, especially for leukemia. There were increased risks of infant mortality and deaths due to congenital malformation in the offspring of male workers. The first witness was summoned to testify in court in November, 2009. Final argument was made on December 12, 2014, and the verdict was announced on April 17, 2015. The Court finds that RCA did expose the former workers at the RCA Plant to mixtures of contaminants, including TCE, tetrachloroethylene, trichloroethane, and methylene chloride. Routes of exposure include drinking groundwater contaminated with those organic solvents. Accepting testimonies of expert witnesses Drs Pau-Chung CHEN (陳保中) and Jung-Der WANG (王榮德), the Court finds that exposures to mixture of organic solvents such as TCE, TCA and their derivatives may result in aggravated harms to human body more hazardous than those caused by exposure to any single chemical within the mixture. RCA and its parent companies knew the health risks of the chemical substances, but they fail to fulfill their responsibility for environmental maintenance and pollution control, and they continue to expose the employees to organic solvents such as carcinogenic trichloroethylene and tetrachloroethylene, causing a large number of workers suffering from diseases. At least 133 people in this litigation have passed away and are still living and suffering from major injuries (including but not limited to cancers). Another group of 1,163 injured laborers and their families have already filed the Taipei District Court on 9 May 2016, requesting a total amount of NT$ 7.3 billion. The Supreme Court of Taiwan has upheld liability of RCA and its mother companies, General Electric, Thomson Electronics and Technicolor on August 16, 2018. The Supreme Court orders them to pay some NT$ 564 million (around US$ eighteen million) in compensation to 262 plaintiffs. For the remaining 246 plaintiffs, the Supreme Court sends the file back to the Taiwan High Court for reconsideration. The Taipei district Court also awarded NT$ 2.3 billion (around US$ 77.5 million) in compensation to the second batch of 1,115 former employees of RCA, Taiwan on December 27, 2019.