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Ultra-processed food consumption has increased worldwide, but associations with cancer risk remain unclear and potential underlying mechanisms are speculative. A robust, multidisciplinary, research agenda is needed to address current research limitations and gaps., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Groundwater poisoning by heavy metals has caused serious health hazards in the exposed population globally. Manganese (Mn) poisoning causing human health hazards is very meagerly reported worldwide. The present research elucidates for the first time the catastrophic effect of manganese causing cancer in the Gangetic plains of Bihar (India). The blood samples of n = 1146 cancer patients were voluntarily obtained for the study, after their consent. Their household water samples were also collected for the study. All the samples were analysed for Mn contamination by Atomic Absorption Spectrophotometer. The study indicates high Mn contamination in the cancer patient blood samples with highest content as 6022 µg/L. Moreover, the cancer patient's household handpump water samples also contained elevated Mn contamination. The correlation coefficient study finds significant association between Mn contamination in blood of cancer patients and their handpump water. The carcinoma group of cancer patients mostly in Stage III & IV had significant Mn contamination in their blood (above WHO/BIS permissible limit). The geospatial study depicts Mn contamination in handpump water in the state of Bihar in correlation with cancer patient's blood samples. This novel finding is being reported in India for the first time, which correlates cancer with handpump drinking water. The long-term Mn exposure could be one of the causative agents for elevating cancer incidences. However, other confounding risk factors cannot be denied., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Vulvar lichen sclerosus (VLS) is a chronic inflammatory mucocutaneous disease known to be associated with human papillomavirus-independent vulvar squamous cell carcinoma. Evidence on the association with other types of cancer, however, is sparce. We conducted a large nationwide cohort study examining the incidence of non-vulvar cancers among women with biopsy-verified VLS compared with the general female population. By using the nationwide Pathology Registry, we identified all women in Denmark with a biopsy-verified VLS diagnosis during 1978-2019 (n = 16,921). The cohort was followed up in the Danish Cancer Registry until 2022 for a subsequent non-vulvar cancer diagnosis. Standardized incidence ratios (SIRs) were computed with 95% confidence intervals (CIs) as relative risk estimates of all specific non-vulvar cancer sites. Compared with general female population rates, women with biopsy-verified VLS had decreased rates of several non-vulvar cancers, including HPV-related cancers (combined estimate: SIR = 0.5; 95% CI: 0.3-0.7), and lung (SIR = 0.6; 95% CI: 0.5-0.7), liver (SIR = 0.5; 95% CI: 0.2-0.9), and thyroid cancer (SIR = 0.5; 95% CI: 0.3-0.9). The decreased SIRs tended to sustain throughout the follow-up period following the VLS diagnosis. This large nationwide cohort study shows that women with biopsy-verified VLS may have a long-term reduced risk of developing HPV-related (cervical, vaginal, oropharyngeal, and anal) and smoking-associated cancers (lung, liver, and cervical) as well as thyroid cancer. Future studies focusing on the mechanisms behind the decreased cancer risk are needed., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Acute inflammation is elicited by lipid and protein mediators in defense of the host following sterile or pathogen-driven injury. A common refrain is that chronic inflammation is a result of incomplete resolution of acute inflammation and behind the etiology of all chronic diseases, including cancer. However, mediators that participate in inflammation are also essential in homeostasis and developmental biology but without eliciting the clinical symptoms of inflammation. This non-inflammatory physiological activity of the so called 'inflammatory' mediators, apparently under the functional balance with anti-inflammatory mediators, is defined as unalamation ( un-ala-mation ). Inflammation in the absence of injury is a result of perturbance in unalamation due to a decrease in the anti-inflammatory mediators rather than an increase in the inflammatory mediators and leads to chronic inflammation. This concept on the etiology of chronic inflammation suggests that treatment of chronic diseases is better achieved by stimulating the endogenous anti-inflammatory mediators instead of inhibiting the 'inflammatory' mediator biosynthesis with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Furthermore, both 'inflammatory' and anti-inflammatory mediators are present at higher concentrations in the tumor microenvironment compared to normal tissue environments. Since cancer is a proliferative disorder rather than a degenerative disease, it is proposed that heightened unalamation , rather than chronic inflammation, drives tumor growth. This understanding helps explain the inefficacy of NSAIDs as anticancer agents. Finally, inhibition of anti-inflammatory mediator biosynthesis in tumor tissues could imbalance unalamation toward local acute inflammation triggering an immune response to restore homeostasis and away from tumor growth., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maddipati.)

Tumor-associated macrophages (TAMs) are a phenotypically diverse, highly plastic population of cells in the tumor microenvironment (TME) that have long been known to promote cancer progression. In this review, we summarize TAM ontogeny and polarization, and then explore how TAMs enhance tumor cell migration through the TME, thus facilitating metastasis. We also discuss how chemotherapy and host factors including diet, obesity, and race, impact TAM phenotype and cancer progression. In brief, TAMs induce epithelial-mesenchymal transition (EMT) in tumor cells, giving them a migratory phenotype. They promote extracellular matrix (ECM) remodeling, allowing tumor cells to migrate more easily. TAMs also provide chemotactic signals that promote tumor cell directional migration towards blood vessels, and then participate in the signaling cascade at the blood vessel that allows tumor cells to intravasate and disseminate throughout the body. Furthermore, while chemotherapy can repolarize TAMs to induce an anti-tumor response, these cytotoxic drugs can also lead to macrophage-mediated tumor relapse and metastasis. Patient response to chemotherapy may be dependent on patient-specific factors such as diet, obesity, and race, as these factors have been shown to alter macrophage phenotype and affect cancer-related outcomes. More research on how chemotherapy and patient-specific factors impact TAMs and cancer progression is needed to refine treatment strategies for cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Friedman-DeLuca, Karagiannis, Condeelis, Oktay and Entenberg.)

Purpose: Beliefs on causes of cancer, although sometimes aligned with known risk factors, may be influenced by personal experiences, cultural narratives, and misinformation. We investigated the prevalence of beliefs on causes of cancer and their association with cancer risk perception and lifestyle in a multiethnic Asian population., Methods: In total, 2,008 Malaysian adults with no previous cancer were surveyed using a 42-item questionnaire adapted from the Awareness Measure and the Cancer Awareness Measure-Mythical Causes Scale. Partial least squares structural equation modeling was used to evaluate measurement models., Results: Despite high educational attainment, only about half of the respondents believed that 7 of the 21 listed established risk factors caused cancer. Factors associated with accurate beliefs included higher socioeconomic status (SES) and having family or friends with cancer. However, 14 of the 21 listed mythical/unproven factors were correctly believed as not cancer-causing by the majority. Women and those with lower SES were more likely to hold misconceptions. Beliefs on established risk factors were significantly associated with perceived risk of cancer. Individuals with stronger beliefs in established risk factors were less likely to be associated with healthy behaviors. Conversely, stronger beliefs in mythical or unproven factors were more likely to be associated with healthy lifestyles., Conclusion: Findings highlight the importance of prioritizing cancer literacy as a key action area in national cancer control plans. The counterintuitive associations between cancer beliefs and lifestyle emphasize the complexity of this relationship, necessitating nuanced approaches to promote cancer literacy and preventive behaviors.

Background: Associations of waist circumferences (WC) and body mass index (BMI) measured once or over time, with cancer incidence were studied. WC is associated with some cancers independent of BMI. Analyses of cumulative central adiposity and cancer are lacking. We investigated associations between waist circumference-years, incorporating exposure time to WC ≥ 102 cm in men or ≥88 cm in women, and cancer, and compared this with single WC or BMI., Methods: Serial WC measurements taken over 9 years in the prospective Atherosclerosis Risk in Communities Study (ARIC) predicted yearly WC. Cox proportional hazards regression estimated hazard ratios (HRs) of cancer incidence for waist circumference-years, WC or BMI, measured in Visit 4. Harrell's C-statistic quantified metric predictive performances., Results: 10,172 participants were followed up from Visit 4 for cancer over a median 13.7 for men and 15.8 years for women. For obesity-related cancers, HRs per standard deviation waist circumference-years were 1.14 (95%CI:1.04,1.25) and 1.19 (95%CI:1.12,1.27), respectively. Differences in metric predictive performances were marginal., Discussion: This is the first study to identify positive associations between waist circumference-years and cancer. Waist circumference-years did not provide additional information on cancer risk beyond that of WC and BMI. BMI is routinely measured in clinic so it may be preferred over WC., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The Institutional Review Boards at each study site approved the ARIC study protocol. Only participants who consented to research on chronic diseases such as cancer were included. Given the use of secondary cohort data, no ethical approval was required for the current analysis. Anonymous data was used and handled as per the data management plan and data transfer agreements [70]., (© 2024. The Author(s).)

The incidence of early-onset cancers in adolescents and young adults (AYA) has been increasing worldwide since the 1990s. In Italy, a significant increased rate of 1.6 % per year has been reported for early-onset cancers among females between 2008 and 2016. This is mainly attributable to melanoma, thyroid, breast and endometrial cancer. The aim of our work was to describe temporal trends of the main established lifestyle risk factors (tobacco use, alcohol consumption, obesity, physical inactivity, dietary westernization and reproductive factors) over the last 20 years in the Italian AYA population. Available data on behavioural risk factors, individual and household daily life have been obtained and elaborated from PASSI, ISTAT and Eurostat reports. Lowering age of smoking initiation, an increase in alcohol drinkers among young females, and an obesity and overweight epidemic, particularly among children and adolescents as a result of physical inactivity and dietary habits, may be contributing factors behind this cancer epidemic, especially among females. In-depth investigations are needed to understand the exact role of each contributing factor, the effects of exposure to nicotine-containing products and environmental factors such as endocrine disruptors that could play a role in this phenomenon., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cancer and metabolic disorders have emerged as major global health challenges, reaching epidemic levels in recent decades. Often viewed as separate issues, metabolic disorders are shown by mounting evidence to heighten cancer risk and incidence. The intricacies underlying this connection are still being unraveled and encompass a complex interplay between metabolites, cancer cells and immune cells within the tumour microenvironment (TME). Here, we outline the interplay between metabolic and immune cell dysfunction in the context of three highly prevalent metabolic disorders, namely obesity; two associated liver diseases, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH); and type 2 diabetes. We focus primarily on macrophages and T cells, the critical roles of which in dictating inflammatory response and immune surveillance in metabolic disorder-associated cancers are widely reported. Moreover, considering the ever-increasing number of patients prescribed with metabolism disorder-altering drugs and diets in recent years, we discuss how these therapies modulate systemic and local immune phenotypes, consequently impacting cancer malignancy. Collectively, unraveling the determinants of metabolic disorder-associated immune landscape and their role in fuelling cancer malignancy will provide a framework essential to therapeutically address these highly prevalent diseases., (© 2024. Springer Nature Limited.)

Background: Adiposity is a known risk factor for certain cancers; however, it is not clear whether the risk of cancer differs between individuals with high adiposity but different metabolic health status. The aim of this systematic literature review and meta-analysis of cohort studies was to evaluate associations between metabolic obesity phenotypes and overall and site-specific cancer risk., Methods: PubMed and Embase databases were used to identify relevant cohort studies up to the 6th of June 2023. Random-effects models were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for the association between metabolic obesity phenotypes and cancer risk. Certainty of evidence was assessed using the Cochrane methods and the GRADE tool. This study is registered with PROSPERO, number CRD42024549511., Results: A total of 15,556 records were screened, and 31 publications covering 15 unique cohort studies were included in this analysis. Of these studies, 22 were evaluated as being at low risk of bias and 9 at moderate risk of bias. Compared to metabolically healthy normal-weight individuals (MHNW), metabolically unhealthy overweight/obese (MUOW/OB) individuals had a higher risk of overall (SRR = 1.21, 95% CI = 1.02-1.44, n = 3 studies, high certainty) and obesity-related cancers (SRR = 1.42, 95% CI = 1.15-1.74, n = 3, very low certainty). Specifically, MUOW/OB individuals were at higher risk of cancers of the postmenopausal breast (SRR = 1.32, 95% CI = 1.17-1.48, n = 7, low certainty), colorectum (SRR = 1.24, 95% CI = 1.16-1.31, n = 6, moderate certainty), endometrium (SRR = 2.31, 95% CI = 2.08-2.57, n = 4, high certainty), thyroid (SRR = 1.42, 95% CI = 1.29-1.57, n = 4, moderate certainty), kidney (SRR = 1.71, 95% CI = 1.40-2.10, n = 3, low certainty), pancreas (SRR = 1.35, 95% CI = 1.24-1.47, n = 3, high certainty), liver (SRR = 1.81, 95% CI = 1.36-2.42, n = 2, moderate certainty), gallbladder (SRR = 1.42, 95% CI = 1.17-1.73, n = 2, high certainty), bladder (SRR = 1.36, 95% CI = 1.19-1.56, n = 2, moderate certainty), and stomach (SRR = 1.50, 95% CI = 1.12-2.01, n = 2, high certainty). In addition, we found elevated risks of most of these cancers among individuals classified as MUNW and MHOW/OB phenotypes compared to those with MHNW phenotype. Our stratified analyses according to metabolic obesity phenotypes suggested that the elevated risks of some cancers were stronger in individuals with MUOW/OB versus those with MHOW/OB or MUNW phenotypes., Conclusion: These findings suggest that both higher adiposity and metabolic dysfunction were independently associated with increased risk of several cancers, with the strongest associations generally observed among those with both metabolic dysfunction and obesity., (© 2024. The Author(s).)

Background: Traffic-related air pollutants have been associated with a variety of adverse human health impacts, including cancers. In the United States, numerous studies have documented racial inequities in neighborhood exposures to traffic-related air pollution. Emerging evidence suggests that structural racism may influence neighborhood exposures to air pollutants. However, existing research has largely focused on residential racial segregation, one indicator of structural racism. This study developed a multidimensional measure of structural racism to examine the relationship between structural racism and estimated cancer risk from air pollutants in Georgia., Methods: Carcinogenic air toxics data were obtained from the US Environmental Protection Agency's 2019 Air Toxics Screening Assessment and sociodemographic data from the American Community Survey. Guided by stakeholder input, county-level data on residential segregation, education, employment, incarceration, economic status, political participation, and homeownership were used to create a multidimensional county-level structural racism index. Relative risks (RRs) were estimated for associations between structural racism and elevated (top 10% in Georgia) estimated cancer risk from air toxics., Results: Multilevel analyses revealed a significant association between multidimensional structural racism and exposure to carcinogenic traffic-related air pollutants. Neighborhoods in the highest quartile of structural racism exhibited an elevated cancer risk from traffic-related air pollutants (RR, 7.84; 95% CI, 5.11-12.05) compared to neighborhoods with lower levels of structural racism., Conclusions: Multidimensional structural racism was associated with estimated cancer risk from traffic-related air pollution in Georgia. Findings can inform future studies and policy interventions that address racial inequalities in exposure to traffic-related air pollution., (© 2024 American Cancer Society.)

Objectives: This meta-analysis aimed to ascertain whether small molecule drugs increase the risk of infection or malignancy in adult IBD patients., Methods: A comprehensive search of eight databases was conducted from their inception to November 2023. The risk of infections or malignancies in adult IBD patients treated with JAK inhibitors and S1P receptor modulators was compared. Fixed-effects or random-effects models were performed, and relative risk (RR) and 95 % confidence interval (CI) were calculated., Results: 27 RCTs from 14 studies were included (n = 10,623). The evidence indicates that small molecule drugs increase the risk of any infections (RR: 1.23, 95 %CI: 1.05-1.44) and herpes zoster (RR: 2.23, 95 %CI: 1.39-3.57). Specifically, UC patients on Filgotinib and Tofacitinib, and CD patients on Upadacitinib, showed elevated risks of any infections (RR: 1.27, 95 % CI: 1.04-1.56; RR: 1.42, 95 % CI: 1.16-1.75; RR: 1.57, 95 % CI: 1.11-2.22). CD patients on Upadacitinib also had a significantly higher risk of herpes zoster (RR: 2.64, 95 %CI: 1.16-5.99). No infections were associated with S1P receptor modulators, and similarly, no malignancies were linked to small molecule drugs., Conclusions: JAK inhibitors increase the risk of any infections and herpes zoster Over a one-year follow-up period in IBD patients. Continuous monitoring of their long-term safety is necessary., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a growing global health concern with significant implications for oncogenesis. This review synthesizes current evidence on the association between MASLD and cancer risk, highlighting its role as a risk factor for both intrahepatic and extrahepatic malignancies. MASLD is increasingly recognized as a major cause of hepatocellular carcinoma (HCC), with its incidence rising in parallel with the prevalence of metabolic dysfunction. Furthermore, MASLD is associated with an elevated risk of various gastrointestinal cancers, including colorectal, esophageal, stomach, and pancreatic cancers. Beyond the digestive tract, evidence suggests that MASLD may also contribute to an increased risk of other cancers such as breast, prostate, thyroid, gynecological, renal and lung cancers. Understanding the mechanisms underlying these associations and the impact of MASLD on cancer risk is crucial for developing targeted screening and prevention strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zobair Younossi reports a relationship with Gilead Sciences, Intercept, NovoNordisk, BMS, Abbvie, Merck, Madrigal, Genfit, Siemens, BMS, Terns and Viking that includes: consulting or advisory and funding grants. If there are other authors, they 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 Inc.)

Objective: Increasing evidence has shown that dietary behaviors are closely correlated with the carcinogenesis and progression of many types of cancer. However, few studies have assessed the global diet-related burden of cancer. This study aimed to estimate the pooled burdens and trends of five types of cancers attributable to dietary behaviors., Methods: Data regarding cancer attributable to dietary behaviors were extracted from the Global Burden of Disease study 2019, including the death cases and age-standardized death rates, and disability-adjusted life years (DALYs) estimated according to diseases, age, sex, the socio-demographic index (SDI) and location., Results: According to the Global Burden of Disease study 2019, five types of cancer were affected by dietary behaviors: colon and rectum cancer; tracheal, bronchus and lung cancer; stomach cancer; esophageal cancer and breast cancer. Unhealthy dietary behaviors for cancer caused a total of 605.4 thousand deaths and 13951.3 thousand DALYs globally. The burden of cancer attributable to dietary risks was higher for men than for women. The highest age-standardized death rates in 2019 were observed in southern Latin America, and the lowest rates were observed in North Africa and the Middle East. The greatest increases in the age-standardized death rates, from 1990 to 2019, were found in Western Sub-Saharan Africa, with the greatest decreases in Central Asia. The highest attributable proportions of death or DALYs were colon and rectum cancer. The greatest diet-related cancer burden was observed in regions with a high-middle SDI., Conclusion: Global age-standardized deaths and DALYs rates attributable to diet-related cancer are considerable and cause a substantial burden. Successful population-wide initiatives targeting unhealthy dietary behaviors would reduce this burden., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Potentially modifiable cancer risk factors have been increasingly recognized among the Chinese population. In this study, we aimed to investigate the perceived significance of these risk factors among senior nursing officers, who play a crucial role in providing healthcare services. We also sought to determine senior nursing officers' performance in reducing these risk factors., Methods: A questionnaire survey regarding 23 potentially modifiable cancer risk factors was conducted in November 2023 with 58 senior nursing officers at Taizhou Hospital in Zhejiang Province, China. The consistent fuzzy preference relation method and importance-performance analysis were used to determine the attribute weights and performance levels., Results: The senior nursing officers considered diabetes, ultraviolet radiation exposure, PM 2.5 exposure, excess body weight, physical inactivity, alcohol consumption and secondhand smoking significant. However, performance in reducing secondhand smoking, physical inactivity, excess body weight, PM 2.5 exposure, and ultraviolet radiation exposure required improvement., Conclusions: The proposed hybrid multiple-criteria decision-making model enhances our understanding of the perceived significance of 23 modifiable cancer risk factors and performance in reducing them, which could facilitate improvements in health education efforts., (© 2024. The Author(s).)

Determining a novel etiology and mechanism of human cancer requires extraction of characteristic mutational signatures derived from chemical substances. This study explored the mutational signatures of N -nitroso bile acid conjugates using Salmonella strains. Exposing S. typhimurium TA1535 to N -nitroso-glycine/taurine bile acid conjugates induced a predominance of C:G to T:A transitions. Two mutational signatures, B1 and B2, were extracted. Signature B1 is associated with N -nitroso-glycine bile acid conjugates, while Signature B2 is linked to N -nitroso-taurine bile acid conjugates. Signature B1 revealed a strong transcribed strand bias with GCC and GCT contexts, and the mutation pattern of N -nitroso-glycine bile acid conjugates in YG7108, which lacks O 6 -methylguanine DNA methyltransferases, matched that of the wild-type strain TA1535, suggesting that O 6 -methyl-deoxyguanosine contributes to mutations in the relevant regions. COSMIC database-based similarity analysis revealed that Signature B1 closely resembled SBS42, which is associated with occupational cholangiocarcinoma caused by overexposure to 1,2-dichlolopropane (1,2-DCP) and/or dichloromethane (DCM). Moreover, the inflammatory response pathway was induced by 1,2-DCP exposure in a human cholangiocyte cell line, and iNOS expression was positive in occupational cholangiocarcinomas. These results suggest that 1,2-DCP triggers an inflammatory response in biliary epithelial cells by upregulating iNOS and N -nitroso-glycine bile acid conjugate production, resulting in cholangiocarcinoma via DNA adduct formation.

Background: Urticaria has been tentatively linked to cancer, but epidemiological evidence supporting this link is sparse and conflicting. We conducted a population-based cohort study using healthcare databases covering the Danish population (January 1980-December 2022). We followed 87 507 people for a median of 10.1 years after their first hospital contact for urticaria., Objectives: To examine associations of a hospital diagnosis of urticaria with incident cancer., Methods: We computed the absolute risk of cancer and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) standardized to Danish national cancer rates. In a cross-sectional analysis, we examined whether the extent of cancer spread differed between people with vs. without a previous urticaria diagnosis., Results: The overall SIR for all types of cancer was 1.09 (95% CI 1.06-1.11) based on 7788 observed vs. 7161 expected cases. The risk for any cancer was 0.7% (95% CI 0.6-0.7) for the first year of follow-up. Cancer was diagnosed in 588 people with urticaria during the first year of follow-up (SIR 1.49, 95% CI 1.38-1.62) and in 7200 people thereafter (SIR 1.06, 95% CI 1.04-1.09). During the first year of follow-up, we found strong associations with haematological cancers (e.g. non-Hodgkin lymphoma; SIR 2.91, 95% CI 1.92-4.23). Cancer stage was similar in people with vs. without a previous urticaria diagnosis., Conclusions: At the time of urticaria diagnosis, or in the first year afterward, we found a large increase in the risk of cancer. In subsequent years, a persistent 6% increase in risk remained. Diagnostic efforts may partly explain the elevated short-term risk, but occult cancer may promote urticaria, or cancer and urticaria share common risk factors., Competing Interests: Conflicts of interest The Department of Clinical Epidemiology, Aarhus University, receives funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Obesity is as an important risk factor for chronic diseases. Metabolically healthy obesity (MHO) is considered a benign state. The association between metabolic health and obesity categories and cancer risk remains unclear. This study aimed to investigate the relationship between metabolic health status combined with obesity phenotypes and the risk of cancer., Methods: Data from 91,834 participants in the Kailuan cohort were analyzed, excluding individuals with a body mass index (BMI) < 18.5 kg/m² and those with a history of cancer. Obesity phenotypes were classified based on BMI and waist circumference (WC) combined with metabolic health status, resulting in six phenotypes. Cox proportional hazard regression models were used to assess the association between metabolic health and obesity phenotypes with cancer risk and all-cause mortality., Results: The prevalence of metabolically healthy obesity and metabolically unhealthy obesity defined by BMI was 6.86% and 12.18%, while that defined by WC was 20.79% and 25.76%, respectively. Compared to metabolically healthy participants, individuals with an unhealthy metabolic status had a significantly higher risk of cancer (HR, 1.09; 95% CI, 1.03-1.15; p=0.004). The hazard ratios for cancer were 1.19, 1.23, 1.20, and 1.55 for individuals with one, two, three, and four metabolic disorders, respectively. Among those classified as metabolically unhealthy, both overweight and obesity were associated with a protective effect on cancer risk (HR, 0.88; 95% CI, 0.80-0.96; p=0.006 for overweight; HR, 0.87; 95% CI, 0.78-0.97; p=0.010 for obesity). However, abdominal obesity significantly increased cancer risk in both metabolically healthy and unhealthy participants. In subgroup analysis, simple obesity showed a protective trend against cancer in those with respiratory cancers, while abdominal obesity consistently posed a risk for various cancer types., Conclusion: Metabolically unhealthy status and abdominal obesity are risk factors for cancer and all-cause mortality, whereas simple obesity offers protective effects against cancer and all-cause mortality in metabolically unhealthy individuals. These findings suggest that maintaining metabolic health and reducing the metabolic risks associated with abdominal obesity should be key targets for cancer prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Wang, Chen, Liu, Liu, Lin, Xie, Ma, Wang, Shi, Zhang, Yang, Liu, Deng, Zhang and Shi.)

Background: Common Variable Immunodeficiency (CVID) represents a heterogenic group of primary immunodeficiencies (PID) characterized by impaired antibody production and susceptibility to infections. Non-infectious complications, such as autoimmune diseases, lymphoproliferative disorders, and malignancies, now significantly impact prognosis. Moreover, both hematologic and solid organ malignancies are more frequently observed in CVID patients compared to other PIDs. The risk factors for carcinogenesis in CVID remain largely unknown., Objective: This multicenter study aims to characterize the clinical profile of cancer in CVID patients in Spain and to identify independent risk factors associated with malignancy development, focusing on the role of immune dysregulation., Methods: A nationwide, cross-sectional study was conducted from November 2019 to May 2022, involving 17 hospitals treating PID patients in Spain. Data were collected systematically on demographics, infectious and non-infectious comorbidities, immunological parameters, and treatment. Statistical analysis, including multivariate logistic regression, was performed to identify risk factors associated to malignancy., Results: Of 250 CVID patients, 38 (15.26%) were diagnosed with cancer, predominantly non-Hodgkin lymphoma, gastric cancer, and lung adenocarcinoma. Cancer patients were significantly older (mean age 60.70 vs. 49.36 years, p<0.001) and had higher rates of immune dysregulation (81.58% vs. 59.7%, p=0.01). Immune dysregulation was an independent risk factor for cancer (OR 2.19, p=0.04), alongside previous immunosuppressant therapy (OR 2, p=0.031), higher IgM levels (OR 1.008 per SD, p=0.012), older age (OR 1.04, p<0.001), and lower CD4 cell counts at diagnosis (OR 0.997, p<0.001)., Conclusions: This study highlights the increased cancer risk in CVID patients, with immune dysregulation, prior immunosuppressant use, elevated IgM levels, and lower CD4 cell counts as conjointly associated. These findings underscore the need for vigilant cancer screening and tailored management strategies in CVID patients to improve outcomes. Future research should focus on elucidating the molecular mechanisms linking immune dysregulation and malignancy in CVID., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cabañero-Navalon, Garcia-Bustos, Balastegui-Martin, Bracke, Mateu, Solanich, Carrillo-Linares, Robles-Marhuenda, Puchades, Pelaez Ballesta, Lopez-Osle, Torralba-Cabeza, Bielsa Masdeu, Gil Niño, Tornador Gaya, Castellanos, Sánchez-Martínez, Barragán-Casas, González-García, Patier de la Peña, López-Wolf, Rufete, Canovas Mora and Moral Moral.)

The collapse of the World Trade Center (WTC) buildings in New York City generated a large plume of dust and smoke. WTC dust contained human carcinogens including metals, asbestos, polycyclic aromatic hydrocarbons (PAHs), persistent organic pollutants (POPs, including polychlorinated biphenyls (PCBs) and dioxins), and benzene. Excess levels of many of these carcinogens have been detected in biological samples of WTC-exposed persons, for whom cancer risk is elevated. As confirmed in this structured literature review (n studies = 80), all carcinogens present in the settled WTC dust (metals, asbestos, benzene, PAHs, POPs) have previously been shown to be associated with DNA methylation dysregulation of key cancer-related genes and pathways. DNA methylation is, therefore, a likely molecular mechanism through which WTC exposures may influence the process of carcinogenesis.

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.)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is spreading worldwide, largely due to unhealthy lifestyles that contribute to the rise in diabetes, metabolic syndrome, and obesity. In this situation, the progression of injury to metabolic steatohepatitis can evolve to cirrhosis and, eventually, to hepatocellular carcinoma (HCC). It is well known that serine protease enzymes with different functions in cellular homeostasis act as signaling molecules that regulate liver inflammation by activating the protease-activated receptors (PARs) family members, expressed on the cellular plasma membrane. Among them, PAR2 plays a central role in the activation of signaling pathways in response to changes in the extracellular microenvironment. Experimental data have provided evidence that PAR2 is involved not only in inflammatory response but also in insulin resistance, lipid metabolism, and cancer. The major aims of this narrative review are addressed to assess PAR2 involvement in inflammation, metabolism, and liver disease progression and to explore possible therapeutic strategies, based on PAR2 inhibition, in order to prevent its biological effects in the context of MAFLD and cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Villano and Pontisso.)

Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers' development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhong, Zheng, Zhao, Wang, Su, Zhong, Wang and Shi.)

Background: De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol-related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation., Methods: From 1990 to 2015, all patients transplanted for ALD were included., Results: A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years., Conclusion: Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non-modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD., (© 2024 The Author(s). Clinical Transplantation published by Wiley Periodicals LLC.)

As the population ages and post-transplant survival improves, pretransplant and post-transplant malignancy are becoming increasingly common. In addition, rapid advances in cancer therapies and improving outcomes prompt us to rethink pretransplant cancer-free wait time and screening strategies. Although kidney transplant recipients (KTRs) are at higher risk of developing cancer, epidemiological data on how to best screen and treat cancers in KTRs are incomplete. Thus, current recommendations are still largely on the basis of studies in the general population, and their validity in KTRs is uncertain. Kidney transplant candidates without prior cancer should be evaluated for latent malignancies even in the absence of symptoms. Conversely, individuals with a history of malignancy require thorough monitoring to detect potential recurrences or de novo malignancies. When treating KTRs with cancer, reducing immunosuppression can enhance antitumor immunity, yet this also increases the risk of graft rejection. Optimal treatment and immunosuppression management remains undefined. As the emergence of novel cancer therapies adds complexity to this challenge, individualized risk-benefit assessment is crucial. In this review, we discuss up-to-date data on pretransplant screening and cancer-free wait time, as well as post-transplant cancer screening, prevention strategies, and treatment, including novel therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

The switch/sucrose non-fermentable (SWI/SNF) subfamily are evolutionarily conserved, ATP-dependent chromatin-remodelling complexes that alter nucleosome position and regulate a spectrum of nuclear processes, including gene expression, DNA replication, DNA damage repair, genome stability and tumour suppression. These complexes, through their ATP-dependent chromatin remodelling, contribute to the dynamic regulation of genetic information and the maintenance of cellular processes essential for normal cellular function and overall genomic integrity. Mutations in SWI/SNF subunits are detected in 25% of human malignancies, indicating that efficient functioning of this complex is required to prevent tumourigenesis in diverse tissues. During development, SWI/SNF subunits help establish and maintain gene expression patterns essential for proper cellular identity and function, including maintenance of lineage-specific enhancers. Moreover, specific molecular signatures associated with SWI/SNF mutations, including disruption of SWI/SNF activity at enhancers, evasion of G0 cell cycle arrest, induction of cellular plasticity through pro-oncogene activation and Polycomb group (PcG) complex antagonism, are linked to the initiation and progression of carcinogenesis. Here, we review the molecular insights into the aetiology of human malignancies driven by disruption of the SWI/SNF complex and correlate these mechanisms to their developmental functions. Finally, we discuss the therapeutic potential of targeting SWI/SNF subunits in cancer.

Background: Cancer is a global medical challenge, and research is at its peak to understand the unique mechanisms of cancer cells. The expanding field of epidemiology, including molecular and environmental studies, helps us better understand the distribution of molecular changes and environmental risk factors in the population., Aim: In the present review, we aimed to find out the different genes and environmental factors that are associated with different cancers in the Jammu & Kashmir (J&K) region of the North Indian population., Method: A Systematic approach of literature survey was used to curate research data based on genetic and environmental epidemiology specifying the J&K region., Result: Of 640 articles found initially and screening of 490 records, 97 studies were included for the final review. It was observed that numerous genes that are strongly linked to various cancer types have been discovered as a result of the rising genotyping trend, which has grown in the demography exponentially over the last few decades. The majority of these genes are related to cell cycle regulation, cell growth signaling, and apoptosis regulation. Additionally, high promoter hypermethylation of various genes which were found to be attributed to the presence of distinct dietary patterns. The most important environmental risk attributes were salt tea consumption and dried pickles., Discussion & Conclusion: In conclusion, the J&K population possesses many common polymorphisms in various genes with a small effect size that makes individuals more prone to different forms of cancers interacting with different environmental factors. What we can't do is, change the gene sequence or molecular changes which are the main changes for determining the susceptibility of any altered condition but what we can do is lower/ limit the exposure to the environmental factors which is a key element playing with the susceptibility's threshold. Therefore, limiting exposure to environmental factors could be a major step in lowering the risk of disease.

Background: Subsequent short-latency leukemias are well-described among survivors of childhood cancer. However, late (5-14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort., Methods: Subsequent leukemias, among 25,656 five-year survivors, were self-reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures., Results: Seventy-seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 years, range 5.0-14.5 years) and 28 with VLL (median time from diagnosis 25.4 years, range 15.9-42.8 years), with a cumulative incidence of 0.23% (95% CI 0.18%-0.30%) 20 years from diagnosis for all subsequent leukemias. The most common leukemia subtypes were acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. Compared to the general population, survivors were at increased risk, for developing LL (SIR 9.3, 95% CI 7.0-12.1) and VLL (SIR 5.9, 95% CI 3.9-8.4). In multivariable relative risk analyses, cumulative epipodophyllotoxin dose >4000 mg/m 2 was associated with increased risk for LL and VLL (RR 4.5, 95% CI 2.0-9.9)., Conclusions: In this large series of late subsequent leukemias, survivors of childhood cancer are at increased risk, with no evidence of plateau over time. We observed most risk among survivors who received high cumulative doses of epipodophyllotoxins. Ongoing consideration for this late effect should continue beyond 10 years., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Epidemiologic and genetic studies have now defined specific patterns of incidence and distinct molecular features of cancers in young versus aging people. Here, I review a general framework for the causes of cancer in children and young adults by relating somatic genetic mosaicism and developmental tissue mutagenesis. This framework suggests how aging-associated cancers such as carcinomas, glioblastomas, and myelodysplastic leukemias are causally distinct from cancers that predominantly affect children and young adults, including lymphoblastic and myeloid leukemias, sarcomas, neuroblastomas, medulloblastomas, and other developmental cancers. I discuss the oncogenic activities of known developmental mutators RAG1/2, AID, and PGBD5, and describe strategies needed to define missing developmental causes of young-onset cancers. Thus, a precise understanding of the mechanisms of tissue-specific somatic mosaicism, developmental mutators, and their control by human genetic variation and environmental exposures is needed for improved strategies for cancer screening, prevention, and treatment., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)

Background: Tobacco smoking is still frequent in Italy and a major cause of cancer globally. We estimated the burden of smoking-related cancer in Italy., Methods: To calculate the population attributable fraction (PAF), we adopted a counterfactual scenario for which all individuals never smoked. The PAF of current and former smoking and second-hand smoke (SHS) was estimated for cancers associated with these habits according to the International Agency for Research on Cancer. Relative risk estimates and prevalence of exposure were derived from large-scale studies and national surveys, respectively. A 20-year latency period between exposure and cancer was considered. Cancer incidence data for 2020 and mortality data for 2017 were obtained from the Italian Association of Cancer Registries., Results: Tobacco smoking caused, in men and women respectively, 90.0 % and 58.3 % of lung; 67.8 % and 53.5 % of pharyngeal; 47.0 % and 32.2 % of bladder; 45.9 % and 31.7 % of oral; 36.6 % and 23.6 % of esophageal; 23.0 % and 14.0 % of pancreatic cancer and lower percentages of cancers at other sites. Tobacco smoking accounted for 23.9 % and 7.7 % of new cancer cases in 2020, and 32.1 % and 11.3 % of cancer deaths in 2017 in men and women, respectively, corresponding to 17.3 % of cases and 24.5 % of cancer deaths overall. The PAF of lung cancer due to SHS in never smoking women married with smokers was 13.0 %., Conclusions: Tobacco smoking is a primary cause of cancer in Italy in both sexes. Tobacco control policies are warranted., 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 article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alcohol consumption can cause, beyond addiction, roughly 200 different diseases and at least fourteen types of cancer. In 2016 the WHO estimated that 29% of alcohol-related deaths were mainly due to oncological diseases, liver cirrhosis (20%), and cardiovascular disorders (19%). The aim of this review was to focus on the absorption and metabolism of ethanol and discuss the main conditions caused by alcohol consumption (i.e., liver and cardiovascular diseases, and tumors). This narrative review is based on a detailed analysis of the scientific literature published before January 31, 2024 (PubMed, Web of Science, Scopus, Google Scholar). Approximately 90% of the absorbed alcohol reaches the liver where it is metabolized to acetaldehyde, a highly reactive and toxic compound. The excessive use of alcohol causes damage to several organs and systems, mainly the liver (e.g., steatosis, steato-hepatitis, fibrosis, and cirrhosis), cardiovascular system (cardiomyopathy, arrythmias, arterial hypertension, and stroke), and significantly contribute to the onset of neoplastic lesions to various organs including the esophagus, liver and breast. Even moderate drinking appears not to reduce mortality risk. Alcohol intake is one of the main risk factors for several pathological conditions and social problems, thus drastically impacting on public health. Proper awareness of the high risk related to alcohol consumption is of crucial importance to reduce the harm to public health.

Diabesity is a condition where an individual has both diabetes and obesity, which can lead to severe complications including cardiovascular disease, a leading cause of mortality. Recently, cancer has become a leading cause of excess hospitalizations, and both diabetes and obesity are associated with a higher risk of developing several types of cancer. In this review, we propose that chronic stress significantly increases this association. Managing diabetes and obesity is challenging as they both cause significant distress. The relationship between stress and cancer is interconnected, with anxiety and depression being common in cancer patients. Cancer diagnosis and treatment can cause lasting changes in the body's neuroendocrine system, with stress causing an excessive release of catecholamines and prostaglandins in patients undergoing cancer surgery, which promotes the spread of cancer to other parts of the body. Furthermore, stress could significantly increase the risk of cancer in patients with diabetes, obesity, or both., (© 2024. The Author(s).)

With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are largely unknown. The Metabolic Dysregulation and Cancer Risk Program: a transdisciplinary approach to obesity-associated cancers (MeDOC) is a trans-National Cancer Institute research initiative supported by the Division of Cancer Control and Population Sciences, the Division of Cancer Biology, the Division of Cancer Prevention, and the Center to Reduce Cancer Health Disparities. The overall purpose of the MeDOC Program is to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and increased obesity cancer risk as well as identify markers that will enhance cancer risk prediction, improve screening for high-risk individuals, and identify targets for preventive and therapeutic interventions for cancer interception or treatment. This report describes the funded research projects, the Coordinating Center, and the goals of the MeDOC program., (Published by Oxford University Press 2024.)

This review aims to critically analyze the pathways of interaction and the pathogenic mechanisms linking periodontitis and oral bacteria with the initiation/progression of cancer at different body compartments. A higher risk of head and neck cancer has been consistently associated with periodontitis. This relationship has been explained by the local promotion of dysbiosis, chronic inflammation, immune evasion, and direct (epi)genetic damage to epithelial cells by periodontal pathobionts and their toxins. Epidemiological reports have also studied a possible link between periodontitis and the incidence of other malignancies at distant sites, such as lung, breast, prostate, and digestive tract cancers. Mechanistically, different pathways have been involved, including the induction of a chronic systemic inflammatory state and the spreading of oral pathobionts with carcinogenic potential. Indeed, periodontitis may promote low-grade systemic inflammation and phenotypic changes in the mononuclear cells, leading to the release of free radicals and cytokines, as well as extracellular matrix degradation, which are all mechanisms involved in carcinogenic and metastatic processes. Moreover, the transient hematogenous spill out or micro-aspiration/swallowing of periodontal bacteria and their virulence factors (i.e., lipopolysaccharides, fimbriae), may lead to non-indigenous bacterial colonization of multiple microenvironments. These events may in turn replenish the tumor-associated microbiome and thus influence the molecular hallmarks of cancer. Particularly, specific strains of oral pathobionts (e.g., Porphyromonas gingivalis and Fusobacterium nucleatum) may translocate through the hematogenous and enteral routes, being implicated in esophageal, gastric, pancreatic, and colorectal tumorigenesis through the modulation of the gastrointestinal antitumor immune system (i.e., tumor-infiltrating T cells) and the increased expression of pro-inflammatory/oncogenic genes. Ultimately, the potential influence of common risk factors, relevant comorbidities, and upstream drivers, such as gerovulnerability to multiple diseases, in explaining the relationship cannot be disregarded. The evidence analyzed here emphasizes the possible relevance of periodontitis in cancer initiation/progression and stimulates future research endeavors., (© 2023 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

Context: Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer., Objective: To describe the rates of childhood neoplasms and cancer after neonatal phototherapy., Data Sources: The CENTRAL, PubMed, Scopus, and Web of Science databases., Study Selection: Observational studies regardless of design were included., Data Extraction: The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools., Results: Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors., Conclusions: Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding., Impact Statement: Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and., (© 2024. The Author(s).)

Metastasis is the leading cause of cancer-related mortality; however, a complete understanding of the molecular programs driving the metastatic cascade is lacking. Metastasis is dependent on collective invasion-a developmental process exploited by many epithelial cancers to establish secondary tumours and promote widespread disease. The key drivers of collective invasion are "Leader Cells", a functionally distinct subpopulation of cells that direct migration, cellular contractility, and lead trailing or follower cells. While a significant body of research has focused on leader cell biology in the traditional context of collective invasion, the influence of metastasis-promoting leader cells is an emerging area of study. This review provides insights into the expanded role of leader cells, detailing emerging evidence on the hybrid epithelial-mesenchymal transition (EMT) state and the phenotypical plasticity exhibited by leader cells. Additionally, we explore the role of leader cells in chemotherapeutic resistance and immune evasion, highlighting their potential as effective and diverse targets for novel cancer therapies.

Background and Aim: The association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data., Methods: Utilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings' validity., Results: Multivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013)., Conclusions: The multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk., (© 2024. The Author(s).)

Introduction: The aim of this study is to investigate how excess weight can influence cancer risk and the possible mechanisms involved. For this purpose, a bibliographic review was made of the studies published between 2000 and 2024 that analyze this relationship, as well as specific types of cancer associated with obesity. A significant association was found between overweight/obesity and increased cancer risk. Some specific cancers such as esophageal, stomach, colorectal, liver, and endometrial cancers, among others, are particularly sensitive to this relationship. Therefore, excess weight is confirmed as an important risk factor for the development of cancer. Maintaining a healthy weight and following healthy lifestyle recommendations are essential to prevent cancer and improve survival in cancer patients.

Objective: Systemic sclerosis (SSc) is associated with an increased risk of cancer. We aimed to assess the prevalence of cancer in our cohort and to explore possible associations with clinical, immunological and treatment characteristics., Methods: Our retrospective monocentric cohort study of patients with SSc recorded prevalent and incident cases of malignancy, including those diagnosed within 3 years of the SSc onset (defined as cancer-associated scleroderma) and sought associations with the clinical characteristics and the serum autoantibody profiling performed using RNA and protein immunoprecipitation, Western-blot, immunoblot and ELISA at the time of SSc diagnosis, prior to any specific treatment., Results: Among 290 patients with SSc, the overall prevalence of cancer was 20%, with 8% of cases being cancer-associated scleroderma. Both conditions were more frequent in elderly patients and in patients with positive anti-Ro52 or anti-U3-RNP. Cancer-associated scleroderma was significantly more prevalent among patients negative for both anti-centromere (ACA) and anti-topoisomerase-1 (TOPO1) antibodies, especially in the case of diffuse SSc. Immunosuppressants were not significantly associated with cancer. Patients triple negative for ACA, TOPO1 and anti-RNA polymerase III antibodies had a significantly higher risk of breast cancer., Conclusions: Cancer surveillance should be particularly careful in patients with diffuse SSc, increased age at disease onset and without classical SSc-related autoantibodies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maier, Castiglioni, Petrelli, Cannatelli, Ferretti, Pellegrino, Sarzi Puttini, Fiorina and Ardizzone.)

While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case-control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8-77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89-4.95) and those with the highest intake (169.1-331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45-2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI) < 23 kg/m 2 and never smokers than BMI ≥ 23 kg/m 2 and ever smokers (P's heterogeneity  = 0.003 and 0.021, respectively) but found in both never and ever-drinkers of alcohol (P heterogeneity  = 0.001). A U-shaped association between selenium intake and cancer risk was seen in cancer sites of the stomach, colon, rectum, and lung cancers. In summary, we found a U-shaped association between selenium intake and cancer risk and a safe selenium intake (mean: 117.8 µg/day) in the Vietnamese population. Further mechanistic investigation is warranted to understand better a U-shaped association between selenium intake and cancer risk., (© 2024. The Author(s).)

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Cause-of-Death-Registry. A total of 664 patients were followed for a median of 7.7 years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx ( p = 0.53). During a median follow-up of 7.7 years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stenman, Wallinder, Holmberg, Karason, Magnusson and Dellgren.)

Lung transplantation (LTx) is a well-known treatment for end-stage lung disease. This study aimed to report the incidence of cancer after LTx and long-term outcome among lung transplant recipients with a pretransplant diagnosis of cancer. Patients who underwent LTx between 1990-2016 were included in the study. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer Registry and the Cause-of-Death registry. A total of 614 patients were followed for a median of 5.1 years. In all, 159 malignancies were diagnosed. The excess risk of cancer or standardized incidence ratio (SIR) following LTx was 5.6-fold compared to the general Swedish population. The most common malignancies were non-melanoma skin cancer (NMSC) (SIR 76.5 (95%CI 61.7-94.8); non-Hodgkin lymphoma (SIR 23.5, 95%CI 14.8-37.2); and lung cancer (SIR 8.89, 95%CI 5.67-13.9). There was no significant difference in overall survival between those with and without a history of cancer before LTx (p = 0.56). In total, 159 malignancies were identified after LTx, which was a 5.6-fold higher relative to the general population. A history of previous cancer yields similar survival in selected recipients, compared to those without cancer prior to LTx., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stenman, Wallinder, Holmberg, Karason, Magnusson and Dellgren.)

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).)

Background: The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or 'endozepine') increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer., Methods: We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing., Results: Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers., Conclusion: These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance., (© 2024. The Author(s).)

Abstract: The development of agents for cancer prevention is a lengthy process requiring a delicate balance between the safety and tolerability of potential interventions and effectiveness in preventing future cancer. Individuals at risk for a specific cancer are frequently at risk for multiple types of cancer as well as other chronic diseases, especially ones associated with aging. Shared environmental exposures, genetic predisposition, metabolic factors, and commonalities in pathogenesis suggest opportunities for combined targeting of cancer and other chronic diseases. Examples discussed here include mechanisms shared between various cancers and obesity, diabetes, and cardiovascular disease., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Over the past 2 decades, the search for dietary factors for developing cancer prevention guidelines has led to a significant expansion in the study of dietary patterns and their relation to cancer. Dietary patterns, which consider the types, amounts, variety, and combination of consumed foods, may encompass additive, synergistic, or interactive effects on human health, compared with individual nutrients or foods. In this review, we discuss the history and methodologies of dietary pattern research, describe common dietary indices used in cancer research, and summarize the existing evidence on dietary patterns and cancer risk. Current evidence supports the beneficial role of dietary patterns that are rich in vegetables, legumes, whole fruit, and whole grains and limited in added sugars, refined grains, processed foods, and red and processed meat in preventing various cancers, including breast, colorectal, and prostate cancers. Additionally, emerging evidence suggests that dietary patterns based on biological mechanisms, such as hyperinsulinemic diet and inflammatory diet, hold promise and may be priority areas for future research., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. E.L.G. is funded as an American Cancer Society Clinical Research Professor (grant CRP-23-1014041)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The objective of this review was to assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of the most investigated neoplastic diseases., Methods: Eligibility criteria: We included cohort and case-control studies of neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of hand-held transceivers or RF-emitting equipment in the workplace (SR-C). While no restrictions on tumour type were applied, in the current paper we focus on incidence-based studies of selected "critical" neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). We focussed on investigations of specific neoplasms in relation to specific exposure sources (i.e. E-O pairs), noting that a single article may address multiple E-O pairs., Information Sources: Eligible studies were identified by literature searches through Medline, Embase, and EMF-Portal. Risk-of-bias (RoB) assessment: We used a tailored version of the Office of Health Assessment and Translation (OHAT) RoB tool to evaluate each study's internal validity. At the summary RoB step, studies were classified into three tiers according to their overall potential for bias (low, moderate and high)., Data Synthesis: We synthesized the study results using random effects restricted maximum likelihood (REML) models (overall and subgroup meta-analyses of dichotomous and categorical exposure variables), and weighted mixed effects models (dose-response meta-analyses of lifetime exposure intensity). Evidence assessment: Confidence in evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach., Results: We included 63 aetiological articles, published between 1994 and 2022, with participants from 22 countries, reporting on 119 different E-O pairs. RF-EMF exposure from mobile phones (ever or regular use vs no or non-regular use) was not associated with an increased risk of glioma [meta-estimate of the relative risk (mRR) = 1.01, 95 % CI = 0.89-1.13), meningioma (mRR = 0.92, 95 % CI = 0.82-1.02), acoustic neuroma (mRR = 1.03, 95 % CI = 0.85-1.24), pituitary tumours (mRR = 0.81, 95 % CI = 0.61-1.06), salivary gland tumours (mRR = 0.91, 95 % CI = 0.78-1.06), or paediatric (children, adolescents and young adults) brain tumours (mRR = 1.06, 95 % CI = 0.74-1.51), with variable degree of across-study heterogeneity (I 2  = 0 %-62 %). There was no observable increase in mRRs for the most investigated neoplasms (glioma, meningioma, and acoustic neuroma) with increasing time since start (TSS) use of mobile phones, cumulative call time (CCT), or cumulative number of calls (CNC). Cordless phone use was not significantly associated with risks of glioma [mRR = 1.04, 95 % CI = 0.74-1.46; I 2  = 74 %) meningioma, (mRR = 0.91, 95 % CI = 0.70-1.18; I 2  = 59 %), or acoustic neuroma (mRR = 1.16; 95 % CI = 0.83-1.61; I 2  = 63 %). Exposure from fixed-site transmitters (broadcasting antennas or base stations) was not associated with childhood leukaemia or paediatric brain tumour risks, independently of the level of the modelled RF exposure. Glioma risk was not significantly increased following occupational RF exposure (ever vs never), and no differences were detected between increasing categories of modelled cumulative exposure levels., Discussion: In the sensitivity analyses of glioma, meningioma, and acoustic neuroma risks in relation to mobile phone use (ever use, TSS, CCT, and CNC) the presented results were robust and not affected by changes in study aggregation. In a leave-one-out meta-analyses of glioma risk in relation to mobile phone use we identified one influential study. In subsequent meta-analyses performed after excluding this study, we observed a substantial reduction in the mRR and the heterogeneity between studies, for both the contrast Ever vs Never (regular) use (mRR = 0.96, 95 % CI = 0.87-1.07, I 2  = 47 %), and in the analysis by increasing categories of TSS ("<5 years": mRR = 0.97, 95 % CI = 0.83-1.14, I 2  = 41 %; "5-9 years ": mRR = 0.96, 95 % CI = 0.83-1.11, I 2  = 34 %; "10+ years": mRR = 0.97, 95 % CI = 0.87-1.08, I 2  = 10 %). There was limited variation across studies in RoB for the priority domains (selection/attrition, exposure and outcome information), with the number of studies evenly classified as at low and moderate risk of bias (49 % tier-1 and 51 % tier-2), and no studies classified as at high risk of bias (tier-3). The impact of the biases on the study results (amount and direction) proved difficult to predict, and the RoB tool was inherently unable to account for the effect of competing biases. However, the sensitivity meta-analyses stratified on bias-tier, showed that the heterogeneity observed in our main meta-analyses across studies of glioma and acoustic neuroma in the upper TSS stratum (I 2  = 77 % and 76 %), was explained by the summary RoB-tier. In the tier-1 study subgroup, the mRRs (95 % CI; I 2 ) in long-term (10+ years) users were 0.95 (0.85-1.05; 5.5 %) for glioma, and 1.00 (0.78-1.29; 35 %) for acoustic neuroma. The time-trend simulation studies, evaluated as complementary evidence in line with a triangulation approach for external validity, were consistent in showing that the increased risks observed in some case-control studies were incompatible with the actual incidence rates of glioma/brain cancer observed in several countries and over long periods. Three of these simulation studies consistently reported that RR estimates > 1.5 with a 10+ years induction period were definitely implausible, and could be used to set a "credibility benchmark". In the sensitivity meta-analyses of glioma risk in the upper category of TSS excluding five studies reporting implausible effect sizes, we observed strong reductions in both the mRR [mRR of 0.95 (95 % CI = 0.86-1.05)], and the degree of heterogeneity across studies (I 2  = 3.6 %)., Conclusions: Consistently with the published protocol, our final conclusions were formulated separately for each exposure-outcome combination, and primarily based on the line of evidence with the highest confidence, taking into account the ranking of RF sources by exposure level as inferred from dosimetric studies, and the external coherence with findings from time-trend simulation studies (limited to glioma in relation to mobile phone use). For near field RF-EMF exposure to the head from mobile phone use, there was moderate certainty evidence that it likely does not increase the risk of glioma, meningioma, acoustic neuroma, pituitary tumours, and salivary gland tumours in adults, or of paediatric brain tumours. For near field RF-EMF exposure to the head from cordless phone use, there was low certainty evidence that it may not increase the risk of glioma, meningioma or acoustic neuroma. For whole-body far-field RF-EMF exposure from fixed-site transmitters (broadcasting antennas or base stations), there was moderate certainty evidence that it likely does not increase childhood leukaemia risk and low certainty evidence that it may not increase the risk of paediatric brain tumours. There were no studies eligible for inclusion investigating RF-EMF exposure from fixed-site transmitters and critical tumours in adults. For occupational RF-EMF exposure, there was low certainty evidence that it may not increase the risk of brain cancer/glioma, but there were no included studies of leukemias (the second critical outcome in SR-C). The evidence rating regarding paediatric brain tumours in relation to environmental RF exposure from fixed-site transmitters should be interpreted with caution, due to the small number of studies. Similar interpretative cautions apply to the evidence rating of the relation between glioma/brain cancer and occupational RF exposure, due to differences in exposure sources and metrics across the few included studies., Other: This project was commissioned and partially funded by the World Health Organization (WHO). Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; and ARPANSA as a WHO Collaborating Centre for Radiation Protection., Registration: PROSPERO CRD42021236798. Published protocol: [(Lagorio et al., 2021) DOI https://doi.org/10.1016/j.envint.2021.106828]., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ken Karipidis as part of his employment is involved in the provision of advice to the Australian Commonwealth Government, Australian States and Territories and the general public on the risks and health effects of exposure to ionising and non-ionising radiation. He is also a member of the International Commission on Non-Ionizing Radiation Protection where he contributes in the development and dissemination of science-based advice on limiting exposure to non-ionizing radiation. Mark Elwood has given expert advice on topics in electromagnetic fields and health, and on the objective interpretation of epidemiological and other scientific information, over many years to individuals and groups, including government ministries, environmental regulators, community groups, commercial organisations, and formal inquiries by government and professional groups including parliamentary and legal proceedings. Some of this work has been financially supported, by universities, health care organisations, research bodies, or by government, professional or commercial groups. Some work has been reported ‘blind’, with the client being unidentified. Susanna Lagorio was principal investigator (April 2019 – March 2020) of the research project “BRiC 2018/06 - Systematic reviews of exposure to radiofrequency fields and cancer”, supported by the Italian Workers’ Compensation Authority, a public no-profit entity (grant code I85B19000120005). Her employment duties involved provision of advice on health hazards from exposure to RF-EMF to the Italian Ministry of Health and Higher Health Council (she retired on August 1st, 2023). Martin Röösli’s research is entirely funded by public entities or not for profit foundations. He has served as advisor on potential health effects of exposure to non-ionizing radiation to several national and international public advisory and research steering groups, including the World Health Organization, the International Agency for Research on Cancer, the International Commission on Non-Ionizing Radiation Protection, the Swiss Government (member of the working group “Mobile phone and radiation” and chair of the expert group BERENIS), the German Radiation Protection Commission (member of the committee Non-ionizing Radiation (A6) and member of the working group 5G (A630)) and the Independent Expert Group of the Swedish Radiation Safety Authority. From 2011 to 2018, M.R. was an unpaid member of the foundation board of the Swiss Research Foundation for Electricity and Mobile Communication, a non-profit research foundation at ETH Zurich. Neither industry nor nongovernmental organizations are represented on the scientific board of the foundation. Chris Brzozek as part of his employment is involved in the provision of advice to the Australian Commonwealth Government, Australian States and Territories and the general public on the risks and health effects of exposure to ionising and non-ionising radiation. The other authors declare that they have no known conflicts of interest., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Cancer is generally defined as a disease of aging. With aging, the composition, diversity and functional characteristics of the gut microbiota occur changes, with a decline of beneficial commensal microbes triggered by intrinsic and extrinsic factors (e.g., diet, drugs and chronic health conditions). Nowadays, dysbiosis of the gut microbiota is recognized as a hallmark of cancer. At the same time, aging is accompanied by changes in innate and adaptive immunity, known as immunosenescence, as well as chronic low-grade inflammation, known as inflammaging. The elevated cancer incidence and mortality in the elderly are linked with aging-associated alterations in the gut microbiota that elicit systemic metabolic alterations, leading to immune dysregulation with potentially tumorigenic effects. The gut microbiota and immunosenescence might both affect the response to treatment in cancer patients. In-depth understanding of age-associated alterations in the gut microbiota and immunity will shed light on the risk of cancer development and progression in the elderly. Here, we describe the aging-associated changes of the gut microbiota in cancer, and review the evolving understanding of the gut microbiota-targeted intervention strategies. Furthermore, we summarize the knowledge on the cellular and molecular mechanisms of immunosenescence and its impact on cancer. Finally, we discuss the latest knowledge about the relationships between gut microbiota and immunosenescence, with implications for cancer therapy. Intervention strategies targeting the gut microbiota may attenuate inflammaging and rejuvenate immune function to provide antitumor benefits in elderly patients., 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.)