STUDY OBJECTIVE: To review the tobacco industry's Asian environmental tobacco smoke (ETS) consultants programme, focusing on three key nations: China, Hong Kong, and Malaysia.
METHODS: Systematic keyword and opportunistic website searches of formerly private internal industry documents.
MAIN RESULTS: The release of the 1986 US Surgeon General's report on second hand smoke provoked tobacco companies to prepare for a major threat to their industry. Asian programme activities included conducting national/international symposiums, consultant "road shows" and extensive lobbying and media activities. The industry exploited confounding factors said to be unique to Asian societies such as diet, culture and urban pollution to downplay the health risks of ETS. The industry consultants were said to be "..prepared to do the kinds of things they were recruited to do".
CONCLUSIONS: The programme was successful in blurring the science on ETS and keeping the controversy alive both nationally and internationally. For the duration of the project, it also successfully dissuaded national policy makers from instituting comprehensive bans on smoking in public places.
One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
Rivers, the main source of the domestic water supply in Malaysia, have been threatened by frequent flooding in recent years. This study aims to assess human health risks associated with exposure to concentrated heavy metals in a flood-prone region of Malaysia and investigate the affected individuals' willingness to participate in managing water resources. Hazard indices and cancer risks associated with water contamination by heavy metals have been assessed following the method prescribed by the US Environmental Protection Agency. Yearly data of heavy metal contamination (Cd, Cr, Pb, Zn, Fe), water quality parameters (DO, BOD, COD, pH), and climatic information (annual rainfall, annual temperature) have been collected from the Department of Environment and Meteorological Department of Malaysia, respectively. The inductively coupled plasma mass spectrometry technique has been used by the department of environment for analyzing heavy metal concentration in river water samples. In this study, data from a stratified random sample of households in the affected region were analyzed, using partial least squares structural equation modeling, to predict the link between individuals' perceptions and attitudes about water resources and their willingness to engage in water management program. The health risk estimation indicated that the hazard index values were below the acceptable limit, representing no non-carcinogenic risk to adults and children residing in the study area via oral intake and dermal adsorption of water. However, the calculated value for cancer risk signified possible carcinogenic risks associated with Pb and Cd. In general, contamination due to pollution and flooding tends to increase in the basin region, and appropriate management is needed. The results identified perceived water quality as a significant factor influencing people's attitudes toward involvement in water management programs. As in many developing countries, there is no legal provision guaranteeing public representation in water management in Malaysia. The conclusion discusses the importance of these for the literature and for informing future policy actions.
A survey among beachgoers was conducted to determine the swimming associated health effects experienced and its relationship with beach water exposure behaviour in Morib beach. For beach water exposure behaviour, the highest frequency of visit among the respondents was once a year (41.9%). For ways of water exposure, whole body exposure including head was the highest (38.5%). For duration of water exposure, 30.8% respondents prefer to be in water for about 30 min with low possibilities of accidental ingestion of beach water. A total of 30.8% of beachgoers in Morib beach were reported of having dermal symptoms. Bivariate analysis showed only water activity, water contact and accidental ingestion of beach water showed significant association with swimming associated health effects experienced by swimmers. This study output showed that epidemiological study can be used to identify swimming associated health effects in beach water exposed to faecal contamination.
BACKGROUND: Studies on the effects of outdoor air pollution on the respiratory health of students in tropical countries such as Malaysia are limited.OBJECTIVE: To assess associations between outdoor air pollutants and peak expiratory flow (PEF) and fractional exhaled nitric oxide (FeNO).METHOD: PEF and FeNO levels of 487 students recruited in Melaka and Putrajaya, Malaysia, were measured in April and June 2014. Multiple linear regression with mutual adjustment was used to analyse the associations between exposure to air pollution and health.RESULTS: PEF was significantly associated with ozone for 1-day exposure (β = -13.3 l/min, 95% CI -22.7 to -3.8), carbon monoxide for 2-day exposure (β = -57.2 l/min, 95% CI -90.7 to -23.7) and particulate matter ≦10 μm in diameter for 3-day exposure (β = -6.0 l/min, 95% CI -9.2 to -2.8) and 7-day exposure (β = -8.6 l/min, 95% CI -13.0 to -4.1). Stratified analysis showed that associations between PEF and outdoor air pollutant exposures were similar in students with and without elevated FeNO levels.CONCLUSION: Outdoor air pollution in Malaysia may cause airway obstruction unrelated to eosinophilic airway inflammation among students as measured using FeNO.
For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children's health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects.Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans. What is known: • Very limited reviews are available on how BPA adversely affects children's health. • Previous papers mainly covered two systems in children. What is new: • Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives. • Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood.
The objective of this article is to study the influence of exposure and socio-economic variables on the blood lead level of Malaysian school children. Data on respirable lead and blood lead of 346 school children were obtained from Kuala Lumpur (urban), Kemaman (semi-urban) and Setiu (rural). Respirable lead and blood lead were highest for Kuala Lumpur (95 ng/m3 and 5.26 micrograms/dL) followed by Kemaman (27 ng/m3 and 2.81 micrograms/dL) and Setiu (15 ng/m3 and 2.49 micrograms/dL), and the differences were statistically significant. The percentage of school children with excessive blood lead of 10 micrograms/dL or greater was 6.36% overall, and highest for Kuala Lumpur (11.73%). Regression analyses show that urban children are at higher risk of exhibiting excessive blood lead levels. Kuala Lumpur's school children have a 25 times greater risk of having excessive blood lead levels when compared to Kemaman's and Setiu's school children. Respirable and blood lead were correlated (r = 0.999, p = 0.021). Urban school children acquire higher blood lead levels than their rural and semi-urban counterparts, even after controlling for age, sex, parents' education and income levels. In conclusion, it is time that lead in the Malaysian environment and population be monitored closely, especially its temporal and spatial variability. Only then can a comprehensive preventive strategy be implemented.
Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.
Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.
From the beginning of time, man has lived in a continuous state of interdependence with his environment. If the forces of nature are harnessed well, they are a source of great benefit to mankind, but when this balance is tipped, nature's backlash on man can be quite devastating. In recent times, we have seen many vivid examples of the magnitude of the destructive forces of nature, ranging from massive floods caused by typhoons such as Katrina and Rita, the hundreds of thousands of lives lost by the powerful tsunami and the destruction of the environment by the raging forest fires in Spain and California. Yet man has not learnt his lesson. Often greed, at times gross ignorance and more often than not, just indifference to the effects of his actions on the environment result in man upsetting his balance with the environment. In Malaysia, since 1990, the haze has become a predictable annual occurrence, varying only in its severity and duration. The cause being beyond our control, we are unable to prevent it from happening. However, it is within our means to be ready to take the necessary steps to minimize the effects of the haze on the health of Malaysians. In order to be able to give appropriate advice and to allay the anxiety of the general public, it is necessary to have a clear understanding about the various effects of haze on humans.
Objective: Epidemiological studies have reported the close relationship between risk for lung cancers and air pollution in particular, for non-smoking related lung cancers. However, most studies used residential address as proxies which may not estimate accurately an individual’s air pollution exposure. Therefore, the aim of this study was to identify risk factors such as occupation and mode of transportation associated with lung cancer diagnosis and death. Methods: Subjects with lung cancer (n=514) were evaluated both by chart reviews for clinical data and interviews to determine residential address for ten years, main occupation and main mode of transportation. Annual particulate matter with diameter size less than 2.5 micrometre (PM2.5) concentration were calculated based on particulate matter with diameter size less than 10 micrometre (PM10) data recorded by Malaysian Department of Environment. Logistic regression analysis, cluster analysis and the Cox regression analysis were performed to the studied variables. Results: This study concurred with previous studies that lung adenocarcinoma were diagnosed in predominantly younger, female non-smokers compared to the other types of lung cancers. Lung adenocarcinoma subjects had annual PM2.5 that was almost twice higher than squamous cell carcinoma, small cell carcinoma and other histological subtypes (p=0.024). Independent of smoking, the κ -means cluster analysis revealed two clusters in which the high risk cluster involves occupation risk with air pollution of more than four hours per day, main transportation involving motorcycle and trucks and mean annual PM2.5 concentration of more than 30 based on residential address for more than ten years. The increased risk for the high-risk cluster was more than five times for the diagnosis of lung adenocarcinoma (OR=5.69, 95% CI=3.14-7.21, p<0.001). The hazard ratio for the high-risk cluster was 3.89 (95% CI=2.12-4.56, p=0.02) for lung adenocarcinoma mortality at 1 year. Conclusion: High-risk cluster including PM2.5, occupation risk and mode of transportation as surrogates for air-pollution exposure was identified and highly associated with lung adenocarcinoma diagnosis and 1-year mortality.
Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.
Air pollution is a substantial environmental threat to children and acts as acute and chronic disease risk factors alike. Several studies have previously evaluated epigenetic modifications concerning its exposure across various life stages. However, findings on epigenetic modifications as the consequences of air pollution during childhood are rather minimal. This review evaluated highly relevant studies in the field to analyze the existing literature regarding exposure to air pollution, with a focus on epigenetic alterations during childhood and their connections with respiratory health effects. The search was conducted using readily available electronic databases (PubMed and ScienceDirect) to screen for children's studies on epigenetic mechanisms following either pre- or post-natal exposure to air pollutants. Studies relevant enough and matched the predetermined criteria were chosen to be reviewed. Non-English articles and studies that did not report both air monitoring and epigenetic outcomes in the same article were excluded. The review found that epigenetic changes have been linked with exposure to air pollutants during early life with evidence and reports of how they may deregulate the epigenome balance, thus inducing disease progression in the future. Epigenetic studies evolve as a promising new approach in deciphering the underlying impacts of air pollution on deoxyribonucleic acid (DNA) due to links established between some of these epigenetic mechanisms and illnesses.
Exposure to aflatoxins in the adult Malaysian diet was estimated by analysing aflatoxins in 236 food composites prepared as "ready for consumption". Dietary exposure to aflatoxin B1 (AFB1) ranged from 24.3 to 34.00 ng/kg b.w./day (lower to upper bound), with peanuts being the main contributor. Estimated liver cancer risk from this exposure was 0.61-0.85 cancers/100,000 population/year, contributing 12.4%-17.3% of the liver cancer cases. Excluding AFB1 occurrence data higher than 15 µg/kg reduced exposure by 65%-91% to 2.27-11.99 ng/kg b.w./day, reducing the cancer risk to 0.06-0.30 cancers/100,000 population/year (contributing 1.2%-6.1% liver cancer cases). Reducing further the ML of AFB1 from 15 to 5 µg/kg yielded 3%-7% greater drop in the exposure to 0.47-10.26 ng/kg b.w./day with an estimated risk of 0.01-0.26 cancers/100,000 population/year (0.2%-5.1% liver cancer cases attributed to dietary AFB1). These findings indicate that current MLs are adequate in protecting Malaysians' health.
Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.
Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.
IntroductionMany epidemiological studies have demonstrated associations between air pollution levels and human health in terms of hospital admissions. The aim of this paper is to gather evidence concerning air pollution effects on the risk of hospital admission. We hypothesised that increase in: particulate matter (PM), ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), and sulphur dioxide (SO2) levels would be associated with the increasing trend of hospital admission.MethodsA systematic review of literature was carried out. Literature search was done in Sage, Ovid Medline, Science Direct, Wiley and ProQuest from 2010 to 2016 using keywords "hospital admission and air pollution". Studies of any relevant design were included if they presented original data, included at least one analysis where hospital admission was the specific outcome, and one or more of the following exposures were investigated: PM, O3, CO, NO2 and SO2.ResultsA total of 175 potential studies were identified by the search. Twenty two studies qualified for the review. Air pollution was noted to have an excessive risk of 3.46 (95%CI, 1.67, 5.27) of total hospital admissions. Cardiovascular admission was noted to have an increased risk of hospitalization for PM2.5 of 1.5 to 2.0; PM10 (1.007 to 2.7); NO2 (1.04 to 1.17) and SO2 (1.007). For respiratory admission, PM2.5 can caused an increased risk of hospitalization by 1.1 to 1.8; PM10 (1.007 to 1.13); NO2 (1.08 to 1.94) and SO2 (1.02). While O3 have minimal effect on COPD and stroke, CO does not influence in the effect of these hospitalization.ConclusionThe exposure to air pollutants confers an increased risk of admission of several disease. Our findings call for greater awareness of environmental protection and the implementation of effective measures to improve the quality of air, which may reduce the risks of adverse effects on the population's health.
The adverse effects of traffic-related air pollution on children's respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8-9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00-1.02), NO2 (1.03, 1.00-1.06), PM10 (1.16, 1.04-1.28) and PM2.5 (1.38, 1.08-1.78), all per μg/m3 of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.