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Background: Air pollution-related neoplasms are a major global public health issue and are one of the leading causes of death worldwide. Air pollution is one of the important risk factors of air pollution-related neoplasms and is associated with a variety of air pollution-related neoplasms.The primary objective of this study was to estimate the epidemiological patterns of death rates and disability-adjusted life years (DALYs) associated with air pollution-related neoplasms on a global scale, covering the period from 1990 to 2019. Furthermore, we aimed to predict the trends in these epidemiological patterns up to 2050. By achieving these goals, our study seeks to provide a comprehensive understanding of the potential causes underlying the observed disparities in neoplasm-related health outcomes, ultimately contributing to the development of effective strategies for addressing this major public health issue., Methods: Based on data from the 2019 Global Burden of Disease (GBD) study, the indicators of the air pollution-related neoplasms disease burden was the numbers and age-standardized rates (ASR) of deaths and disability-adjusted life years (DALYs) from 1990 to 2019. First, we compared the burden of air pollution-related neoplasms and temporal trends by gender, age, socio-demographic index (SDI), region, and country. Furthermore, driving factors and improvement potential were evaluated using decomposition and frontier analysis. Finally, forecasting analyses of the changing trend in the burden of air pollution-related neoplasm up to 2050 was conducted based on time series forecasting models., Results: In 2019, air pollution-related neoplasms accounted for 387.45 million (95 % UI 288.04-490.06 million) deaths and 8951.97 million (95 % UI 6680.89-11342.60 million) DALYs globally. Deaths and DALYs demonstrated an upward trend from 1990 to 2019, while their ASR showed a downward trend. The disease burden and the decline degree of males were both significantly higher than that of females, and the high burden was mainly in the elderly groups. The middle SDI region possessed the highest burden with the most significant upward trend, while the high SDI region had the lowest burden with the most significant downward trend. Decomposition analyses represented that the increase in the overall deaths and DALYs of air pollution-related neoplasms was mainly driven by population growth. The predictive analyses expected that the deaths and DALYs of air pollution-related neoplasms will continue to rise, while their corresponding ASR will decrease by 2050., Conclusion: The global burden of air pollution-related neoplasms remained high, and deaths and DALYs will be on upward trends up to 2050, with differences among genders, ages, SDI levels, GBD regions, and countries. It is essential to understand the air pollution-related neoplasm burden and contributing epidemiological factors for implementing effective and factor-tailored interventions to reduce the global burden., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Wildfires have devastating effects on society and public health. However, little evidence from population-based cohort has been performed to analyze the relationship of wildfire-related PM 2.5 , an important component of wildfire smoke, with cancer-specific mortality. We aimed to explore this relationship and identify vulnerable populations in UK with lower levels of wildfire-related PM 2.5 exposure. The study consisted of 492394 participants (age: 38-73 years) recruited by UK Biobank during 2004-2010. The cumulative wildfire-related PM 2.5 within 10 kilometers of residence over three years was used as exposure, which was assessed by chemical transport and machine learning models. A time-varying Cox regression was utilized to explore the relationship of exposure with diverse cancer-specific mortality outcomes. Subgroup analyses of a range of potential modifiers were performed. Each 10 μg/m 3 increment of 3-year cumulative exposure was related to a 0.4 % greater risk of total cancer (95 %CI: 1.001-1.007), a 1.1 % greater risk of lung cancer (95 %CI: 1.004-1.018), and a 2.7 % greater risk of lip, oral cavity and pharynx (LOP) cancer (95 %CI: 1.005-1.049). Higher vulnerability in the wildfire-related PM 2.5 -lung cancer relationship was found among participants being retired than those with other employment status. Even lower levels of exposure to PM 2.5 from wildfires were related to elevated mortality risks for cancer from total, lung, LOP, highlighting the importance of wildfire prevention and control. Further investigations are warranted to enrich and extend existing knowledge in this field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cadmium (Cd) is classified as a class 1 carcinogen by the IARC, yet uncertainty persists regarding the total burden of cancer (incidence and mortality) caused by exposure to it, due to the still limited evidence with regard to its aetiological role in cancer at several body sites., Objectives and Methods: We searched PubMed and EMBASE for meta-analyses and original articles published by February 1st, 2024, that focused on the link between cadmium measured in biological samples (blood, urine, finger-/toe-nails, and hair) and site-specific cancer risk and mortality., Results: We included 9 meta-analyses and 57 original articles (of these, the design was retrospective in 38 and prospective in 19, and Cd levels were quantified in blood, n=33, urine, n=19, both blood and urine, n=2, or finger-/toenail, n=3). Current data consistently suggest a causal role of exposure to cadmium in pancreas, lung, and bladder carcinogenesis. Total cancer risk and mortality are also positively correlated with Cd levels in biological samples. The evidence is weak or inconclusive for the remaining cancer sites (including breast and prostate), mostly due to the limited number of studies available to date and/or methodological limitations., Discussion: Exposure to cadmium poses a risk for increased cancer incidence and mortality. Cadmium-related cancer burden might indeed be currently underestimated, as the amount of available evidence for most cancer sites and types is currently limited, and more research in the field is warranted. Continuing efforts to contain Cd pollution and mitigate associated health risk are also needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated., Objective: This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer., Methods: We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0., Results: A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03)., Conclusion: SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methodological limitations in studying the association between the use of fertility drugs and cancer include the inherent increased risk of cancer in women who never conceive, the increased risk of cancer because of factors (endometriosis and unopposed estrogen) associated with infertility, the low incidence of most of these cancers, and that the diagnosis of cancer is typically several years after fertility drug use. On the basis of available data, there does not appear to be an association between fertility drugs and breast, colon, or cervical cancer. There is no conclusive evidence that fertility drugs increase the risk of uterine cancer, although women with infertility are at higher risk of uterine cancer. There are insufficient data to comment on the risk of melanoma and non-Hodgkin lymphoma associated with fertility drug use. Women should be informed that there may be an increased risk of invasive and borderline ovarian cancers and thyroid cancer associated with fertility treatment. It is difficult to determine whether this risk is related to underlying endometriosis, female infertility, or nulliparity., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Heck, Chen, Van Deventer, Nianogo, Vinceti, Kang, Cockburn, and Federman have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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).

The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA., (© 2024 John Wiley & Sons Ltd.)

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., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Endocrine disrupting chemicals or carcinogens have been known for decades for their endocrine signal disruption. Endocrine disrupting chemicals are a serious concern and they have been included in the top priority toxicants and persistent organic pollutants. Therefore, researchers have been working for a long time to understand their mechanisms of interaction in different human organs. Several reports are available about the carcinogen potential of these chemicals. The presented review is an endeavor to understand the hazard identification associated with endocrine disrupting carcinogens in relation to the human body. The paper discusses the major endocrine disrupting carcinogens and their potency for carcinogenesis. It discusses human exposure, route of entry, carcinogenicity and mechanisms. In addition, the paper discusses the research gaps and bottlenecks associated with the research. Moreover, it discusses the limitations associated with the analytical techniques for detection of endocrine disrupting carcinogens., Competing Interests: Declaration of Competing Interest It is declared that all the authors mutually agreeing to submit this manuscript to the journal. It is also declared that co-authors do not hold any conflict of interest that may affect the publication of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 PM 2.5 samples covering sites with different land uses and our historical pChk1 data for PM 10 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, PM 2.5 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest or potential competing interests associated with this research. The authors have no financial or commercial interests that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 PM 1 , PM 2.5, and PM 10 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 PM 1 , PM 2.5, and PM 10 , 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 PM 1 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 PM 1 , respectively. The effect of PM 1 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Over the past several decades, there have been many epidemiology studies on talc and cancer published in the scientific literature, and several reviews and meta-analyses of talc and respiratory, female reproductive, and stomach cancers, specifically. To help provide a resource for the evaluation of talc as a potential human carcinogen, we applied a consistent set of examination methods and criteria for all epidemiology studies that examined the association between talc exposure (by various routes) and cancers (of various types). We identified 30 cohort, 35 case-control, and 12 pooled studies that evaluated occupational, medicinal, and personal-care product talc exposure and cancers of the respiratory system, the female reproductive tract, the gastrointestinal tract, the urinary system, the lymphohematopoietic system, the prostate, male genital organs, and the central nervous system, as well as skin, eye, bone, connective tissue, peritoneal, and breast cancers. We tabulated study characteristics, quality, and results in a systematic manner, and evaluated all cancer types for which studies of at least three unique populations were available in a narrative review. We focused on study quality aspects most likely to impact the interpretation of results. We found that only one study, of medicinal talc use, evaluated direct exposure measurements for any individuals, though some used semi-quantitative exposure metrics, and few studies adequately assessed potential confounders. The only consistent associations were with ovarian cancer in case-control studies and these associations were likely impacted by recall and potentially other biases. This systematic review indicates that epidemiology studies do not support a causal association between occupational, medicinal, or personal talc exposure and any cancer in humans.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Urbanization has numerous benefits to human society, but some aspects of urban environments, such as air pollution, can negatively affect human health. Two major air pollutants, particulate matter (PM) and polycyclic aromatic hydrocarbons (PAH), have been classified as carcinogens by the International Agency for Research on Cancer. Here, we answer two questions: (1) What are the carcinogenic effects of PM and PAH exposure? (2) How does carcinogenic risk vary across geographical regions? We performed a comprehensive literature search of peer-reviewed published studies examining the link between air pollution and human cancer rates. Focusing on studies published since 2014 when the last IARC monograph on air pollution was published, we converted the extracted data into relative risks and performed subgroup analyses. Exposure to PM 2.5 (per 10 μg/m 3 ) resulted in an 8.5% increase in cancer incidence when all cancer types were combined, and risk for individual cancer types (i.e. lung cancer and adenocarcinoma) was also elevated. PM 2.5 was also associated with 2.5% higher mortality due to cancer when all types of cancer were combined, and for individual cancer types (i.e., lung and breast cancer). Exposure to PM 2.5 and PM 10 posed the greatest risk to lung cancer incidence and mortality in Europe (PM 2.5 RR 2.15; PM 10 RR 1.26); the risk in Asia and the Americas was also elevated. Exposure to PAH and benzo[a]pyrene significantly increased the pooled risk of cancer incidence (10.8% and 8.0% respectively) at the highest percentile of exposure concentration. Our meta-analyses of studies over the past decade shows that urban air pollution in the form of PM 2.5 , PM 10 , and PAH all elevate the incidence and mortality of cancer. We discuss the possible mechanisms of carcinogenesis of PM and PAH. These results support World Health Organization's conclusion that air pollution poses among the greatest health risks to humans living in cities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, we aimed to use the loss of happy life expectancy (LHpLE), an indicator that enables risk assessment considering wellbeing, to compare the risks of environmental carcinogenic chemicals in Japan. First, we surveyed Japanese people to determine their emotional happiness by age and sex and evaluated whether cancer incidence reduced emotional happiness. Questionnaires were administered to a general population panel and a panel of patients with cancer in 2022, recruiting a predetermined number of responses of 5000 and 850, respectively. Second, using the survey data, LHpLE was calculated for radon, arsenic, and fine particulate matter (aerodynamic diameter <2.5 μm; PM 2.5 ) and compared to psychological distress, considering increased mortality and decreased emotional happiness due to these risks. We discovered no significant decrease in emotional happiness due to cancer incidence and no significant associations between emotional happiness and cancer type, history, or stage. LHpLE was calculated to be 6.4 × 10 -3 years for radon, 2.6 × 10 -3 years for arsenic, 1.1 × 10 -2 years (2012 exposure) and 8.6 × 10 -4 years (2020 exposure) for PM 2.5 , and 9.7 × 10 -1 years for psychological distress. The fraction of losses caused by these carcinogenic chemicals to HpLE exceeded 10 -5 , suggesting that risk reduction for these chemicals is important in environmental policies. The LHpLE indicator allows for comparing different types of risks, such as environmental chemicals and psychological distress. This is the first study to compare chemical risks using the LHpLE indicator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to assess Italian consumers' risk of cancer and burden of disease due to dietary exposure to acrylamide. Our model considered six age groups such as infants, toddlers, other children, adolescents, adults, and the elderly, and the consumption of 31 food items. Using a risk-assessment-based approach, we first characterized the risk of neoplastic effects using the margin of exposure method. Then the risk of kidney, endometrial, breast, ovarian cancer, and total cancer was estimated using adjusted cancer slope factors while the burden of disease was quantified using Disability-adjusted Life Years (DALYs). The highest risk for females was related to breast cancer while the lowest was for kidney cancer. We found a comparable risk of total cancer among Italian males and females, estimated at around 1.59 to 3.57 cases per 100,000 individuals annually with the burden ranging between 12.3 - 25.4 and 11.4 - 24.1 DALYs respectively. Our findings provide insights on the multifaceted impact of acrylamide on public health by offering detailed insights into age-specific exposure levels, diverse cancer risks, and the dietary burden of disease related to acrylamide. Targeted interventions and policies can be developed towards mitigating the health risks associated with acrylamide exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Accumulating evidence suggests that domestic water hardness is linked to health outcomes, but its association to all-cause and cause-specific cancers warrants investigation., Objective: The aim of this study was to investigate the association of domestic hard water with all-cause and cause-specific cancers., Methods: In the prospective cohort study, a total of 447,996 participants from UK Biobank who were free of cancer at baseline were included and followed up for 16 y. All-cause and 22 common cause-specific cancer diagnoses were ascertained using hospital inpatient records and self-reported data until 30 November 2022. Domestic water hardness, measured by CaCO 3 concentrations, was obtained from the local water supply companies across England, Scotland, and Wales in 2005. Data were analyzed using Cox proportional hazard models, with adjustments for known measured confounders, including demographic, socioeconomic, clinical, biochemical, lifestyle, and environmental factors., Results: Over a median follow-up of 13.6 y (range: 12.7-14.4 y), 58,028 all-cause cancer events were documented. A U-shaped relationship between domestic water hardness and all-cause cancers was observed ( p for nonlinearity < 0.001 ). In comparison with individuals exposed to soft water ( 0 - 60 mg / L ), the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause cancer were 1.00 (95% CI: 0.98, 1.02) for those exposed to moderate hard water ( > 60 - 120 mg / L ), 0.88 (95% CI: 0.84, 0.91) for those exposed to hard water ( > 120 - 180 mg / L ) and 1.06 (95% CI: 1.04, 1.08) for those exposed to very hard water ( > 180 mg / L ). Additionally, domestic water hardness was associated with 11 of 22 cause-specific cancers, including cancers of the esophagus, stomach, colorectal tract, lung, breast, prostate, and bladder, as well as non-Hodgkin lymphoma, multiple myeloma, malignant melanoma, and hematological malignancies. Moreover, we observed a positive linear relationship between water hardness and bladder cancer., Discussion: Our findings suggest that domestic water hardness was associated with all-cause and multiple cause-specific cancers. Findings from the UK Biobank support a potentially beneficial association between hard water and the incidence of all-cause cancer. However, very hard water may increase the risk of all-cause cancer. https://doi.org/10.1289/EHP13606.

Background: Cannabis use is increasing annually but the relationship between cannabis use and cancer incidence is not uniform because of confounding factors. We aimed to assess the effect of cannabis use on cancer risk using a two-sample Mendelian randomization (MR) approach., Methods: Secondary data analyses were performed on pooled data based on Genome-Wide Association Study (GWAS), selecting data from the ICC and UK-Biobank and 23andMeInc lifetime cannabis use and cannabis use disorder related to the substance use disorders working group from the Psychiatric Genomics Consortium, then selecting highly correlated SNPs as instrumental variables. The substance use disorders working group, iPSYCH, and deCODE GWAS data, and then highly correlated SNPs were selected as instrumental variables for two-sample Mendelian randomization analyses using inverse variance weighting, MR-Egger regression, and weighted median, respectively, to evaluate the relationship between lifetime cannabis use and nine tumors, and subsequently analyzed these results in the same way using cannabis use disorders., Results: The risk of all cancers except breast cancer was not associated with lifetime cannabis use. Our inverse variance weighting method found that lifetime marijuana use reduced the breast cancer risk (P = 0.016, odds ratio [OR] = 0.981), and we subsequently conducted analyses of cannabis use disorders and cancer risk, which showed that cannabis use disorders elevated the risk of breast cancer (P = 0.007, OR = 1.007) as well as the risk of lung cancer (P = 0.014, OR = 1.122)., Conclusion: Large MR analyses suggest that lifetime cannabis use may reduce breast cancer risk, but cannabis use disorder exacerbates the risk of breast and lung cancer. The mechanisms responsible for this outcome remain to be investigated., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer., Methods: The present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy., Results: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74)., Conclusions: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Fifty-two consecutive PM 2.5 samples from December 2021 to February 2022 (the whole winter) were collected in the center of Chongqing, a humid metropolitan city in China. These samples were analysed for the 16 USEPA priority polycyclic aromatic hydrocarbons (16 PAHs) to explore their composition and sources, and to assess their cancer risks to humans. The total concentrations of the 16 PAHs (ng m -3 ) ranged from 16.45 to 174.15, with an average of 59.35 ± 21.45. Positive matrix factorization (PMF) indicated that traffic emissions were the major source (42.4%), followed by coal combustion/industrial emission (31.3%) and petroleum leakage/evaporation (26.3%). The contribution from traffic emission to the 16 PAHs increased from 40.0% in the non-episode days to as high as 46.2% in the air quality episode during the sampling period. The population attributable fraction (PAF) indicates that when the unit relative risk (URR) is 4.49, the number of lung cancer cases per million individuals under PAH exposure is 27 for adults and 38 for seniors, respectively. It was 5 for adults and 7 for seniors, when the URR is 1.3. The average incremental lifetime cancer risk (ILCR) for children, adolescents, adults and seniors was 0.25 × 10 -6 , 0.23 × 10 -6 , 0.71 × 10 -6 , and 1.26 × 10 -6 , respectively. The results of these two models complemented each other well, and both implied acceptable PAH exposure levels. Individual genetic susceptibility and exposure time were identified as the most sensitive parameters. The selection and use of parameters in risk assessment should be further deepened in subsequent studies to enhance the reliability of the assessment results.

The recent scientific focus on polycyclic aromatic hydrocarbons (PAHs) has stemmed from their recognized genotoxic, mutagenic, and carcinogenic properties. This systematic review seeks to evaluate the nexus between exposure to water sources contaminated with PAHs and the associated cancer risk among global populations, encompassing both children and adults. Web of Science (WoS), Cochrane Library, PubMed, ProQuest, Scopus, and Google Scholar, were searched following the PRISMA guidelines, until December 31, 2023. Quality assessment of the selected studies was performed using the Newcastle-Ottawa Scale. The increased lifetime cancer risk (ILCR) attributed to PAH exposure through ingestion and dermal absorption was thoroughly examined across diverse age groups. After extensive searching, screening, and eligibility, 30 articles were included in this review, which was conducted in different parts of the world, including Nigeria (n = 11), China (n = 7), India (n = 4), Iran (n = 3), South Africa (n = 2), Italy (n = 1), Colombia (n = 1), and Iraq (n = 1). Our analysis underscores Nigeria's alarming prevalence of PAH contamination in its rivers, groundwaters, and seawater. Remarkably, the highest cancer risk was identified among children and adults, notably in proximity to the Atlas Cove jetty (seawater) and various Nigerian rivers. This elevated risk is primarily attributed to the combined effects of ingestion and dermal absorption. Furthermore, our findings emphasize the prominent role of combustion-derived and pyrogenic sources of PAH in the examined aquatic ecosystems. This study unequivocally establishes that PAH-contaminated water sources significantly amplify the risk of cancer among both children and adults. The extent of risk variation is influenced by the specific water source, duration of exposure, and age group. Consequently, proactive identification of contaminated water sources and their pollution origins, coupled with targeted educational campaigns, holds promise for reducing the global burden of PAH-related cancer., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Protein kinases play pivotal roles in various biological functions, influencing cell differentiation, promoting survival, and regulating the cell cycle. The disruption of protein kinase activity is intricately linked to pathways in tumor development. This manuscript explores the transformative impact of protein kinase inhibitors on cancer therapy, particularly their efficacy in cases driven by targeted mutations. Focusing on key tyrosine kinase inhibitors (TKIs) like Bcr-Abl, Epidermal Growth Factor Receptor (EGFR), and Vascular Endothelial Growth Factor Receptor (VEGFR), it targets critical kinase families in cancer progression. Clinical trial details of these TKIs offer insights into their therapeutic potentials. Learning from FDA-approved kinase inhibitors, the review dissects trends in kinase drug development since imatinib's paradigm-shifting approval in 2001. TKIs have evolved into pivotal drugs, extending beyond oncology. Ongoing clinical trials explore novel kinase targets, revealing the vast potential within the human kinome. The manuscript provides a detailed analysis of advancements until 2022, discussing the roles of specific oncogenic protein kinases in cancer development and carcinogenesis. Our exploration on PubMed for relevant and significant TKIs undergoing pre-FDA approval phase III clinical trials enriches the discussion with valuable findings. While kinase inhibitors exhibit lower toxicity than traditional chemotherapy in cancer treatment, challenges like resistance and side effects emphasize the necessity of understanding resistance mechanisms, prompting the development of novel inhibitors like osimertinib targeting specific mutant proteins. The review advocates thorough research on effective combination therapies, highlighting the future development of more selective RTKIs to optimize patient-specific cancer treatment and reduce adverse events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atmospheric distribution of polycyclic aromatic hydrocarbons and associated human health risks have been studied in India. However, a comprehensive overview is not available in India, this review highlights the possible sources, and associated cancer risks in people living in different zones of India. Different databases were searched for the scientific literature on polycyclic aromatic hydrocarbons in ambient air in India. Database searches have revealed a total of 55 studies conducted at 139 locations in India in the last 14 years between 1996 and 2018. Based on varying climatic conditions in India, the available data was analysed and distributed with four zone including north, east, west/central and south zones. Comparatively higher concentrations were reported for locations in north zone, than east, west/central and south zones. The average concentrations of ∑PAHs is lower in east zone, and concentrations in north, west/central and south zones are higher by 1.67, 1.47, and 1.12 folds respectively than those in east zone. Certain molecular diagnostic ratios and correlation receptor models were used for identification of possible sources, which aided to the conclusion that both pyrogenic and petrogenic activities are the mixed sources of PAH emissions to the Indian environment. Benzo(a)pyrene toxicity equivalency for different zones is estimated and presented. Estimated Chronic daily intake (CDI) due to inhalation of PAHs and subsequently, cancer risk (CR) is found to be ranging from extremely low to low in various geographical zones of India., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The ten key characteristics (KCs) of carcinogens are based on characteristics of known human carcinogens and encompass many types of endpoints. We propose that an objective review of the large amount of cancer mechanistic evidence for the chemical bisphenol A (BPA) can be achieved through use of these KCs. A search on metabolic and mechanistic data relevant to the carcinogenicity of BPA was conducted and web-based software tools were used to screen and organize the results. We applied the KCs to systematically identify, organize, and summarize mechanistic information for BPA, and to bring relevant carcinogenic mechanisms into focus. For some KCs with very large data sets, we utilized reviews focused on specific endpoints. Over 3000 studies for BPA from various data streams (exposed humans, animals, in vitro and cell-free systems) were identified. Mechanistic data relevant to each of the ten KCs were identified, with receptor-mediated effects, epigenetic alterations, oxidative stress, and cell proliferation being especially data rich. Reactive and bioactive metabolites are also associated with a number of KCs. This review demonstrates how the KCs can be applied to evaluate mechanistic data, especially for data-rich chemicals. While individual entities may have different approaches for the incorporation of mechanistic data in cancer hazard identification, the KCs provide a practical framework for conducting an objective examination of the available mechanistic data without a priori assumptions on mode of action. This analysis of the mechanistic data available for BPA suggests multiple and inter-connected mechanisms through which this chemical can act., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Conflicts of interest Dr S. Chen has received consulting fees from Pfizer, Argenx, Novartis, Scholar Rock, and VisualDx. Dr Y. Semenov is an advisory board member/consultant and has received honoraria from Incyte Corporation, Pfizer, Castle Biosciences, Galderma, and Sanofi outside of the submitted work. The other authors have no conflicts of interest to declare.

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.

Background: Gasoline-powered vehicles and equipment are an important source of air pollution in California. Many gasoline-related pollutants pose significant health concerns. The California Air Resources Board strictly regulates the state's gasoline formulation and vehicle emissions., Objective: To investigate exposure trends for gasoline-related air pollutants between 1996 and 2014, capturing the period before and after the removal of methyl t-butyl ether (MTBE)., Methods: We identified gasoline-related chemicals with known or suspected health concerns and adequate ambient air monitoring data. Average exposures to the general public were estimated from 1996 to 2014 in five major air basins and statewide. We determined the fractions of exposures attributable to gasoline use and evaluated cancer and non-cancer risks for chemicals with available cancer potencies and health reference values., Results: We found that average gasoline-attributable cancer risks for the general California population from the most highly emitted carcinogens (acetaldehyde, benzene, 1,3-butadiene, and formaldehyde) declined by over 80% between 1996 and 2014. This decline occurred despite roughly constant statewide gasoline sales, an increase in vehicle miles traveled, and an approximately 10% increase in vehicle registrations over this same period. Naphthalene, measured as a volatile organic compound (VOC), was the most abundant gasoline-related polycyclic aromatic hydrocarbon (PAH). From 1996 to 2014, gasoline-attributable cancer risks for naphthalene were estimated to drop approximately threefold in the South Coast Air Basin. Exposures to gasoline-related chemicals associated with non-cancer health effects, such as chronic respiratory toxicity or neurotoxicity, were generally below levels of concern. The exception was acrolein, with gasoline-related exposures in 2014 estimated to be high enough to pose risks for respiratory toxicity., Impact Statement: Our historical analysis demonstrated the success of California's regulatory efforts to reduce gasoline-related air pollutant exposures and risks to the general public. New efforts are focused on addressing gasoline-related and other air pollution in heavily impacted communities affected by multiple environmental and social stressors., (© 2023. The Author(s).)

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic persistent chemicals, which are used in many industrial and commercial applications. Hundreds of different PFAS have been identified in the environment and they are commonly found also in human blood. Due to the chemical stability and extensive use, PFAS pose a risk for human health and wildlife. Mounting evidence indicates that PFAS-exposure adversely affects many organs including liver, kidney, and reproductive tissues and induces tumors in laboratory rodents. Epidemiological studies show association between PFAS-exposure and some tumors also in humans. Effects of PFAS-exposure are complex and obviously do not depend only on the concentration and the structure of PFAS, but also on age and sex of the exposed individuals. It has been difficult to show a causal link between PFAS-exposure and tumors. Moreover, molecular mechanisms of the PFAS effects in different tissues are poorly understood. PFAS are not directly mutagenic and they do not induce formation of DNA binding metabolites, and thus are assumed to act more through non-genotoxic mechanisms. In this review, we discuss the involvement of PFAS-compounds in tumor development in tissues where PFAS exposure has been associated with cancer in epidemiological and animal studies (liver, kidney, testicle and breast). We will focus on molecular pathways and mechanisms related to tumor formation following PFAS-exposure., (© 2024. The Author(s).)

Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Long-term use of aspirin has been shown to reduce colorectal cancer risk, but the association remains inconclusive for individual noncolorectal cancers. We examined the association between long-term aspirin use and cancer risk in Denmark., Methods: Using nationwide registries, we followed individuals aged 40-70 years at baseline (January 1, 1997) for cancer diagnoses through 2018. We assessed low-dose (75-150 mg) aspirin use according to continuity, duration, and cumulative amount. In addition, we explored associations with consistent high-dose (500 mg) aspirin use. Using Cox regression, we estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) with aspirin use for overall and site-specific cancer., Results: Among 1 909 531 individuals, 422 778 were diagnosed with cancer during mean follow-up of 18.2 years. Low-dose aspirin use did not reduce the hazard ratio for cancer overall irrespective of continuity and duration of use (continuous use: HR = 1.04, 95% CI = 1.03 to 1.06). However, long-term (≥5 or ≥10 years) use was associated with at least 10% reductions in hazard ratios for several cancer sites: colon, rectum, esophagus, stomach, liver, pancreas, small intestine, head and neck, brain tumors, meningioma, melanoma, thyroid, non-Hodgkin lymphoma, and leukemia. Substantially elevated hazard ratios were found for lung and bladder cancer. In secondary analyses, consistent high-dose aspirin use was associated with reduced hazard ratios for cancer overall (HR = 0.89, 95% CI = 0.85 to 0.93) and for several cancer sites., Conclusion: Long-term low-dose aspirin use was associated with slight to moderately reduced risks for several cancers but not for cancer overall owing to increased risk for some common cancers. Similar or slightly stronger inverse associations were observed for consistent use of high-dose aspirin., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering., Methods: Using the Surveillance, Epidemiology and End Results Medicare-linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s)., Results: There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P = .62) or at any point in the future (OR = 0.96; P = .46)., Conclusions: Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)