Spatial consistency of co-exposure to air and surface water pollution and cancer in China.

Humans can be exposed to multiple pollutants in the air and surface water. These environments are non-static, trans-boundary and correlated, creating a complex network, and significant challenges for research on environmental hazards, especially in real-world cancer research. This article reports on a large study (377 million people in 30 provinces of China) that evaluated the combined impact of air and surface water pollution on cancer. We formulate a spatial evaluation system and a common grading scale for co-pollution measurement, and validate assumptions that air and surface water environments are spatially connected and that cancers of different types tend to cluster in areas where these environments are poorer. We observe "dose-response" relationships in both the number of affected cancer types and the cancer incidence with an increase in degree of co-pollution. We estimate that 62,847 (7.4%) new cases of cancer registered in China in 2016 were attributable to air and surface water pollution, and the majority (69.7%) of these excess cases occurred in areas with the highest level of co-pollution. The findings clearly show that the environment cannot be considered as a set of separate entities. They also support the development of policies for cooperative environmental governance and disease prevention.

Per- and polyfluoroalkyl substances (PFAS) and cancer: Detection methodologies, epidemiological insights, potential carcinogenic mechanisms, and future perspectives.

Per- and polyfluoroalkyl substances (PFAS), known as "forever chemicals," are synthetic chemicals which have been used since the 1940s. Given their remarkable thermostability and chemical stability, PFAS have been widely utilized in commercial products, including textiles, surfactants, food packages, nonstick coatings, and fire-fighting foams. Thus, PFAS are widely distributed worldwide and have been detected in human urine, blood, breast milk, tissues and other substances. Growing concerns over the risks of PFAS, including their toxicity and carcinogenicity, have attracted people's attention. Recent reviews have predominantly emphasized advancements in the detection, adsorption, and degradation of PFAS through their chemical structures and toxic properties; however, further examination of the literature is needed to determine the link between PFAS exposure and cancer risk. Here, we introduced different PFAS detection methods based on sensors and liquid chromatography-mass spectrometry (LC-MS). Then, we discussed epidemiological investigations on PFAS levels and cancer risks in recent years, as well as the mechanisms underlying the carcinogenesis. Finally, we proposed the "4C principles" for ongoing exploration and refinement in this field. This review highlights PFAS-cancer associations to fill knowledge gaps and provide evidence-based strategies for future research.

Effects of pesticide exposure on the expression of selected genes in normal and cancer samples: Identification of predictive biomarkers for risk assessment.

Pesticides pivotal in controlling pests, can represent a threat for human health. Regulatory agencies constantly monitor their harmful effects, regulating their use. Several studies support a positive association between long-term exposure to pesticides and chronic pathologies, such as cancer. Geno-toxicological biomonitoring has proven to be valuable to assess genetic risks associated with exposure to pesticides, representing a promising tool to improve preventive measures and identify workers at higher risk. In this study, a differential gene expression analysis of 70 candidate genes deregulated upon pesticide exposure, was performed in 10 GEO human gene expression DataSets. It was found that six genes (PMAIP1, GCLM, CD36, SQSTM1, ABCC3, NR4A2) had significant AUC predictive values. Also, CD36 was upregulated in non-transformed cell samples and healthy workers, but downregulated in cancer cells. Further validation in larger groups of workers will corroborate the importance of the identified candidates as biomarkers of exposure/effect.

In vivo Evaluation of Antioxidant Activity of Chamomile Extract against Procyclidine-Induced Oxidative Stress: Potential Application in Cancer Prevention.

The study aimed to investigate the effect of the aqueous extract of the chamomile plant on oxidative stress induced by procyclidine in rats. 30 rats were randomly divided into five groups, with 6 rats in each group. The first group was given distilled water only, while the second group was administered procyclidine (1 mg/kg body weight) in three doses daily for a period of 60 days. The third group was given procyclidine in the same doses as the second group for 30 days. Afterward, they were administered an aqueous extract of chamomile (300 mg/kg) for another 30 days. The fourth group was administered the aqueous extract (300 mg/kg) for 30 days. Subsequently, they were given procyclidine in the same doses as the second group for another 30 days. On the other hand, the fifth group was administered the aqueous extract of chamomile (300 mg/kg) for a period of 60 days to investigate the potential effects of the extract. Afterward, blood samples were drawn to measure various biological parameters, including Total Oxidant Status (TOS), Malondialdehyde (MDA), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Acetylcholinesterase (AChE) activity. Finally, an anatomical study was conducted on the kidneys, brain, and liver to enhance the research. The results displayed a significant increase in the levels of TOS, MDA, AST, ALT enzymes, and Ach-E activity in the second group compared to the first group. Groups 3 and 4 significantly decreased compared to the second group based on the same standards. In regard to Group 5, there are no significant moral differences between it and Group 1. Finally, this study demonstrated the importance of using chamomile extract as an antioxidant and its potential in cancer prevention against the oxidative stress induced by excessive doses of procyclidine. (p ≤ 0.005).

Application of an in vitro new approach methodology to determine relative cancer potency factors of air pollutants based on whole mixtures.

Air pollution is an example of a complex environmental mixture with different biological activities, making risk assessment challenging. Current cancer risk assessment strategies that focus on individual pollutants may overlook interactions among them, potentially underestimating health risks. Therefore, a shift towards the evaluation of whole mixtures is essential for accurate risk assessment. This study presents the application of an in vitro New Approach Methodology (NAM) to estimate relative cancer potency factors of whole mixtures, with a focus on organic pollutants associated with air particulate matter (PM). Using concentration-dependent activation of the DNA damage-signaling protein checkpoint kinase 1 (pChk1) as a readout, we compared two modeling approaches, the Hill equation and the benchmark dose (BMD) method, to derive Mixture Potency Factors (MPFs). MPFs were determined for five PM2.5 samples covering sites with different land uses and our historical pChk1 data for PM10 samples and Standard Reference Materials. Our results showed a concentration-dependent increase in pChk1 by all samples and a higher potency compared to the reference compound benzo[a]pyrene. The MPFs derived from the Hill equation ranged from 128 to 9793, while those from BMD modeling ranged from 70 to 303. Despite the differences in magnitude, a consistency in the relative order of potencies was observed. Notably, PM2.5 samples from sites strongly impacted by biomass burning had the highest MPFs. Although discrepancies were observed between the two modeling approaches for whole mixture samples, relative potency factors for individual PAHs were more consistent. We conclude that differences in the shape of the concentration-response curves and how MPFs are derived explain the observed differences in model agreement for complex mixtures and individual PAHs. This research contributes to the advancement of predictive toxicology and highlights the feasibility of transitioning from assessing individual agents to whole mixture assessment for accurate cancer risk assessment and public health protection.

In silico attempt to reveal the link between cancer development and combined exposure to the maize herbicides: Glyphosate, nicosulfuron, S-metolachlor and terbuthylazine.

Pesticides are crucial for crop protection and have seen a 50 % increase in use in the last decade. Besides preventing significant crop losses their use has raised health concerns due to consumer exposure through residues in food and water. The toxicity data from individual components is often used to assess overall mixture toxicity, but uncertainty persists in understanding the behaviors of individual chemicals within these mixtures. Assessing the risk of pesticide mixture exposure remains challenging, potentially leading to overestimation or underestimation of toxicity. This study aims to establish a possible link between exposure to a herbicide mixture and genotoxic effects, focusing on cancer development. Our analysis was focused on four herbicides glyphosate, nicosulfuron, S-metolachlor and terbuthylazine. To determine the link between genes associated with cancer development due to exposure to herbicide mixture, a CTD database tools were used. Through the ToppFun tool molecular function and biological process associated with genes common to the disease of interest and selected herbicides were evaluated. And finally, GeneMANIA was used in order to analyze the function and interaction between common genes of herbicide mixture. Among the 7 common genes for herbicide mixture and cancer development coexpression characteristics were dominant at 65.41 %, 22.14 % of annotated genes shared the same pathway and 7.88 % showed co-localization. Among six target genes involved in genetic disease development co-expression was dominant at 87.34 %, colocalization at 8.03 % and shared protein domains at 4.52 %. Comprehensive molecular analyses, encompassing genomics, proteomics, and pathway analysis, are essential to unravel the specific mechanisms involved in the context of the studied mixture and its potential carcinogenic effects.

The toxicological analysis and safety assessment of heavy metals (Hg, Pb, Cd, and As) in food for special medical purposes (FSMP) available in Polish pharmacies for oncological patients.

The presence of heavy metals in food products may seem an archaic concern; however, our study reveals that the risk is significant, unexpectedly in Food for Special Medical Purposes (FSMP) for oncology patients available in Polish pharmacies. This investigation fills that gap through a detailed toxicological analysis and health risk assessment of these heavy metals in FSMP products (n = 23) using inductively coupled plasma mass spectrometry (ICP-MS). Our comprehensive risk assessment involved evaluating (1) the concentrations of As, Cd, Hg, and Pb in both liquid and powdered FSMP formulations, (2) the amount of heavy metals ingested per serving as specified by the manufacturer, and (3) the cumulative daily and weekly intake adjusted for body weight, benchmarked against the provisional tolerable weekly intake (PTWI). While most samples were below PTWI limits, Cd levels raised concerns due to potential cumulative exposure risks, particularly for oncology patients consuming these products regularly. This study underscores the hidden dangers of heavy metal contamination in FSMP, emphasizing the need for vigilant monitoring and stringent regulatory frameworks to ensure patient safety. By uncovering these latent risks through meticulous toxicological assessment, our research provides crucial insights that could safeguard vulnerable populations. This study is significant due to concerns related to the complex risk assessment of FSMP for cancer patients, considering the complexity of oncological diseases and other comorbid factors, as well as the verification of available legal and regulatory acts of FSMP at the European Community level.

The alarming link between environmental microplastics and health hazards with special emphasis on cancer.

Microplastic contamination is a burgeoning environmental issue that poses serious threats to animal and human health. Microplastics enter the human body through nasal, dermal, and oral routes to contaminate multiple organs. Studies have advocated the existence of microplastics in human breast milk, sputum, faeces, and blood. Microplastics can find their ways to the sub-cellular moiety via active and passive approaches. At cellular level, microplastics follow clathrin and caveolae-dependent pathways to invade the sub-cellular environment. These environmental contaminants modulate the epigenetic control of gene expression, status of inflammatory mediators, redox homeostasis, cell-cycle proteins, and mimic the endocrine mediators like estrogen and androgen to fuel carcinogenesis. Furthermore, epidemiological studies have suggested potential links between the exposure to microplastics and the onset of various chronic diseases. Microplastics trigger uncontrolled cell proliferation and ensue tissue growth leading to various cancers affecting the lungs, blood, breasts, prostate, and ovaries. Additionally, such contamination can potentially affect sub-cellular signaling and injure multiple organs. In essence, numerous reports have claimed microplastic-induced toxicity and tumorigenesis in human and model animals. Nonetheless, the underlying molecular mechanism is still elusive and warrants further investigations. This review provides a comprehensive analysis of microplastics, covering their sources, chemistry, human exposure routes, toxicity, and carcinogenic potential at the molecular level.

Identifying high-risk volatile organic compounds in residences of Chinese megacities: A comprehensive health-risk assessment.

Indoor volatile organic compounds (VOCs) pose considerable health hazards. However, research on hazardous VOCs in Chinese residences has been conducted on a limited spectrum. This study used Monte Carlo simulations with data from Beijing, Shanghai, and Shenzhen to assess VOC health risks in Chinese homes. We identified high-risk VOCs and analyzed the impact of geographic location, age group, activity duration, and inhalation rate on VOC exposure, including lifetime risks. Formaldehyde, acrolein, naphthalene, and benzene posed the highest risks. Notably, acrolein made the leading contribution to non-cancer risks across all megacities. Naphthalene had elevated cancer and non-cancer risks in Shenzhen. This study highlights the need to investigate acrolein and naphthalene, which are currently unregulated but pose substantial health risks. The cumulative cancer risk (TCR) decreases from adults to children, while the cumulative non-cancer risk (HI) is higher for children. In all cities, the average TCR for adults exceeds the tolerable threshold of 10-4, and the average HI values surpass the safety threshold of 1. Nearly 100 % of the population faces a lifetime cancer risk above 10-4, and over 71 % face a non-cancer risk exceeding 10 (tenfold the benchmark). This study underscores the critical need for developing control strategies tailored to VOCs.

Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC Monographs experience.

OBJECTIVES: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) Monographs on the Identification of Carcinogenic Hazards. METHODS: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies. RESULTS: The case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents' specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies. CONCLUSIONS: Exposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.

Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis.

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

Carcinogenicity of asbestos-free talc and talcum powder: A systematic review of the epidemiological evidence after the 2006 monograph of the International Agency for Research on Cancer.

BACKGROUND: in 2006, the International Agency for Research on Cancer (IARC) concluded that the evidence of carcinogenicity for asbestos-free talc was inadequate (group 3), whereas perineal use of talcum powder was classified as possibly carcinogenic (group 2B). OBJECTIVES: to assess whether later studies provide more solid information on the carcinogenic risk from asbestos-free talc and talcum powder and a better characterization of exposure. DESIGN: systematic review. METHODS: cohort studies of talc miners and millers exposed to asbestos-free talc, as well as cohort and case-control studies reporting cancer risk in talc powder consumers published from 2006 onwards were identified through PubMed and reference lists. Pooled analyses were included, but not reviews and meta-analyses. In the case of repeatedly reported studies, the article with the longest follow-up or the largest number of observed cases was selected for data abstraction. Notice was taken of studies which were both reported individually and included in pooled analyses. RESULTS: publications meeting inclusion criteria were: 2 cohort studies on talc miners and millers, 10 cohort studies on talcum powder users (4 of which estimated ovarian cancer risk), and 14 case-control studies (13 on ovarian and 1 on endometrial cancer) on the risk from talcum powder use. No excess cancer mortality has been reported among asbestos-free talc miners and millers. Case-control studies consistently led to estimates of ovarian cancer excesses associated with the use of perineal talcum powder (odds ratios up to 1.5). Most studies quantifying exposure also provided evidence of a dose-response relationship. Individual cohort studies estimated hazard ratios (HR) just above 1. In an analysis of pooled cohorts for a total of 3,112 cases, the HR for women with patent reproductive tract was 1.13 (95%CI 1.01-1.26) with a correlation between HR and frequency of use (p for trend 0.03). In all cohort studies, the perineal use of talcum powder was measured only once in the early phases of follow-up, thus producing an inaccurate measure of cumulative exposure. Results of epidemiological studies regarding cancer risk in other organs are limited and inconsistent. CONCLUSIONS: epidemiological studies updated or published after IARC 2006 evaluation indicate that: no increase in cancer risk is apparent among miners and millers of asbestos-free talc; risk for ovarian cancer increases following the perineal use of commercial talcum powder. A correlation between indicators of quantity of use and cancer risk is suggested by a number of studies. The composition of talcum powders considered in such studies is not known.

Understanding the link between aspartame and cancer.

INTRODUCTION: Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results. AREAS COVERED: Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer. EXPERT OPINION: The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health.

Cancer incidence in Swedish oil refinery workers exposed to benzene.

BACKGROUND: Oil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers' exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma. AIM: The objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries. METHODS: Cancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35-47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. RESULTS: In total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95-1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18-4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1-31.1). DISCUSSION: The study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure. CONCLUSION: The present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.

Talc and human cancer: a systematic review of the experimental animal and mechanistic evidence.

The potential carcinogenicity of talc has been evaluated in many studies in humans and experimental animals published in the scientific literature over the last several decades, with a number of these studies reporting no associations between talc exposure and any type of cancer. In order to fully understand the current state of the science regarding the potential for talc to induce human cancers, we conducted a comprehensive and systematic review of the available experimental animal and mechanistic evidence (in conjunction with a systematic review of the epidemiology evidence in a companion analysis) to evaluate whether it supports talc as being carcinogenic to humans. We considered study quality and its impact on the interpretation of results and evaluated all types of cancer and all exposure routes. We also evaluated the evidence on the potential for talc to migrate in the body to potential tumor sites. We identified seven experimental animal carcinogenicity studies and 11 mechanistic studies of talc to systematically review. We found that several of the experimental animal carcinogenicity studies of talc have limitations that preclude their sensitivity to detect increases in tumor incidence. Regardless, the studies cover multiple exposure routes, species, and exposure durations, and none indicate that talc is a carcinogen in experimental animals except in rats under conditions of extremely high exposure that likely resulted in lung particle overload, a nonspecific effect of high exposures to poorly soluble particles, and not from any carcinogenic properties of talc. Lung particle overload leading to lung tumor formation has only been observed in rats and not in any other species, including humans. The mechanistic studies indicate that talc is not genotoxic or mutagenic, but can induce some effects that could be events on a possible pathway to carcinogenicity, mainly at high exposures or in in vitro studies with exposures of unclear relevance in vivo, but these effects are not consistent across studies and cell types. This systematic review of the experimental animal carcinogenicity and mechanistic evidence for talc indicates that an association between talc exposure and cancer is not expected in humans. Talc carcinogenicity is not plausible in any species except rats, and only when the exposure conditions are high enough to induce lung particle overload, which is not relevant to human exposures.

Global, regional, and national burden of cancers attributable to particulate matter pollution from 1990 to 2019 and projection to 2050: Worsening or improving?

Particulate matter pollution (PMP) has been identified as a substantial contributor to cancer. However, accurately delineating the evolving trends in cancer burden attributable to PMP remains an ongoing challenge. The 1990-2019 disability-adjusted life years (DALYs) were used for cancers attributable to PMP from the Global Burden and Disease Study (GBD) 2019, including ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP). The joinpoint regression and the Bayesian age-period-cohort (BAPC) model were employed to assess the corresponding trends over the periods 1990-2019 and 2020-2050, respectively. Additionally, statistical models such as frontier analysis and health inequality analysis were also utilized. During the 30-year period, cancer DALYs attributable to APMP increased globally, while those attributable to HAP and PMP decreased. Cancer DALYs attributable to APMP were positively correlated with socio-demographic index (SDI), while those attributable to PMP and HAP were negatively correlated with SDI. Frontier analysis identified the countries and regions requiring urgent action to mitigate PMP-attributable cancer. Finally, it was anticipated that the cancer burden attributable to APMP would increase during 2020 to 2050, while the burden attributable to HAP and PMP would decrease. This study conducted an epidemiological investigation of the burden of cancer attributable to APMP, HAP and PMP in various regions and populations worldwide, providing epidemiological insights into the global burden of cancer attributable to PMP and guiding policy and research directions.

Maternal Exposure to Heavy Metals From Industrial Sources During Pregnancy and Childhood Cancer Risk in California.

OBJECTIVE: The study investigated maternal exposure to heavy metals from industrial sources during pregnancy as potential risk factors for childhood cancer. METHODS: Cases ages 0-19 were identified from California Cancer Registry. Controls (20:1 ratio) were randomly selected from California Birth Registry, frequency-matched by birth year (1998-2016). We estimated maternal exposure to lead, nickel, and cobalt in ambient air from the Toxics Release Inventory. We examined "ever/never" and "high/low" exposures categorized by median exposure. Models were adjusted for maternal age, race/ethnicity, method of payment for prenatal care, neighborhood socioeconomic status, and urban/rural residence. RESULTS: Among highly exposed persons, lead was associated with an increased teratoma risk (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 0.97, 2.37), whereas nickel was associated with an increased rhabdomyosarcoma risk (aOR: 1.45; 95% CI: 1.03, 2.04). Cobalt was associated with an increased glioma risk (aOR: 2.25; 95% CI: 1.39, 3.65) among ever-exposed persons. Inverse associations were found between Wilms tumor and nickel among the ever exposed and highly exposed (ever: aOR: 0.75; 95% CI: 0.59, 0.96; high: aOR: 0.64; 95% CI: 0.45, 0.93). CONCLUSIONS: Findings suggest that air pollution from heavy metals released by industrial sources may elevate childhood cancer risk.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

Arsenic inorganic exposure, metabolism, genetic biomarkers and its impact on human health: A mini-review.

Inorganic arsenic species exist in the environment as a result of both natural sources, such as volcanic and geothermal activities, and geological formations, as well as anthropogenic activities, including smelting, exploration of fossil fuels, coal burning, mining, and the use of pesticides. These species deposit in water, rocks, soil, sediments, and the atmosphere. Arsenic-contaminated drinking water is a global public health issue because of its natural prevalence and toxicity. Therefore, chronic exposure to arsenic can have deleterious effect on humans, including cancer and other diseases. This work describes the mechanisms of environmental exposure to arsenic, molecular regulatory factors involved in its metabolism, genetic polymorphisms affecting individual susceptibility and the toxic effects of arsenic on human health (oxidative stress, DNA damage and cancer). We conclude that the role of single nucleotide variants affecting urinary excretion of arsenic metabolites are highly relevant and can be used as biomarkers of the intracellular retention rates of arsenic, showing new avenues of research in this field.