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Pathological germline variants (PGVs) of RAD51D increase the risk of breast and ovarian cancer. In East Asia, c.270_271dup is the most frequently detected PGV of RAD51D; however, only a few cases have been reported in Japan. We report four cancer cases with a germline RAD51D c.270_271dup PGV. Three of them (lung cancer: 2, oral cancer: 1) were incidentally identified by whole genome sequencing in patients negative for the associated cancer histories, homologous recombination (HR) deficiency, or a second hit of RAD51D in the cancer DNA. For genetic counseling, we provided information on surveillance and cascade testing based on Western guidelines. The PGVs of moderate‐risk HR‐related genes are difficult to detect based on phenotype, especially in male‐predominant pedigrees. The current spread of cancer genomic analysis will increase opportunities for incidental variant identification. The establishment of Japanese guidelines is expected to aid in the management of PGV carriers of moderate‐risk genes. [ABSTRACT FROM AUTHOR]

Polychlorinated Biphenyls (PCBs) represent organic contaminants that are persistent hazardous, carcinogenic, and genotoxic, thereby endangering both human well‐being and the ecosystem. This research delved into concentration patterns, sources, and health hazards associated with PCBs in dust collected from vehicle parks in Lagos metropolis. PCBs in samples of Lagos park dust extended from 1.00 to 36.80 ng/g, with PCB 18 exhibiting the highest mean concentration of 17.02 ng/g. Among the 12 PCBs studied, 5 Cl atom PCBs contributed the highest percentage, constituting 30% of the total PCB content in Lagos park dust. Dioxin‐like PCBs (DLPCBs) made up 27% of the overall PCBs composition in the dust. Using the positive matrix factorization method, eight sources of PCBs were identified, with biomass combustion contributing the highest proportion at 42% of the total PCB emissions. Health risk estimates revealed that the magnitude of PCBs exposure in human followed the order: ingestion > dermal contact > inhalation. PCBs exposure through ingestion in children was 9.33 times higher than that of adults, potentially attributed to the inadvertent intake of dust particles by children via hand‐to‐mouth contact. Cancer risk assessments for all PCB congeners remained below 10−6, indicating acceptable risk levels. PCB 18 had the highest cancer risk values, reaching 8.69 × 10−9 for children and 1.19 × 10−9 for adults. [ABSTRACT FROM AUTHOR]

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results: Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype. [ABSTRACT FROM AUTHOR]

Due to rapid urbanization and industrial growth, groundwater globally is continuously deteriorating, posing significant health risks to humans. This study employed a comprehensive methodology to analyze groundwater in the Western Banat Plain (Serbia). Using Piper and Gibbs plots, hydrogeochemistry was assessed, while the entropy‐weighted water quality index (EWQI) was used to evaluate groundwater quality. Pollution sources were identified using positive matrix factorization (PMF) accompanied by Pearson correlation and hierarchical cluster analysis, while Monte Carlo simulation assessed health risks associated with groundwater consumption. Results showed that groundwater, mainly Ca–Mg–HCO3 type, is mostly suitable for drinking. Geogenic pollution, agricultural activities, and sewage were major pollution sources. Consumption of contaminated groundwater poses serious non‐carcinogenic and carcinogenic health risks. Additionally, arsenic from geogenic source was found to be the main health risks contributor, considering its worryingly elevated concentration, ranging up to 364 μg/L. These findings will be valuable for decision‐makers and researchers in managing groundwater vulnerability. Practitioner Points: Groundwater is severely contaminated with As in the northern part of the study area.The predominant hydrochemical type of groundwater in the area is Ca–Mg–HCO3.The PMF method apportioned three groundwater pollution sources.Monte Carlo identified rock dissolution as the primary health risk contributor.Health risks and mortality in the study area are positively correlated. [ABSTRACT FROM AUTHOR]

Eosinophils exhibit anti‐tumor cytotoxic responses in the tumor microenvironment and may contribute to tumor immunosurveillance. To assess the relationship between circulating eosinophils and cancer risk, we analyzed data from 443,542 adults aged 38–73 in the UK Biobank, who were initially cancer‐free, had over a year of follow‐up, and baseline white blood cell count measurements. Using multivariable Cox regression, we estimated hazard ratios (aHR) and 95% confidence intervals (95%CI) for each quartile increase in absolute eosinophil count (AEC) across 58 cancer types, adjusting for relevant confounders. During a median follow‐up of 5.8 years, 22,747 incident cancer cases were diagnosed. We observed an inverse association, which met Bonferroni significance, between AEC and overall cancer risk (aHR, 95%CI 0.97, 0.95–0.98). Notably, 16 cancer types showed borderline associations (p <.05) with AEC, with 12 types displaying an inverse relationship. These included four hematologic cancers (acute and other myeloid leukemia, other lymphocytic leukemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma; aHR range; 0.58–0.87) and eight nonhematologic cancers (melanoma and nose/middle ear, soft tissue/heart, gum/other mouth, tongue, lung, colon, and breast cancers; aHR range: 0.65–0.95). Higher AEC showed a borderline significant association with increased risk for intrahepatic bile duct cancer, Hodgkin lymphoma, diffuse large B‐cell lymphoma, and chronic myeloid leukemia (aHR range: 1.13–1.42). Our study, the largest to date, provides insights into the relationship between blood eosinophils and a comprehensive list of incident cancers. The inverse association between AEC and overall cancer risk suggests a protective role for eosinophils in tumor surveillance. [ABSTRACT FROM AUTHOR]

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. Significant associations were observed between high levels of structural racism and estimated cancer risk from traffic‐related air pollution. These findings can inform policy interventions that address racial inequalities in exposure to traffic‐related air pollution. [ABSTRACT FROM AUTHOR]

Background: Currently recommended cancer screening programs address only part of the overall population cancer burden. Even populations deemed high‐risk for certain individual cancers experience a considerable potential burden of other cancers. However, few published cancer screening trials report the incidence of untargeted cancers. Methods: The National Lung Screening Trial (NLST), initiated in 2002–2004, was a randomized controlled trial of lung cancer screening in adults with ≥30 pack‐years of smoking. Active follow‐up for incident invasive cancers continued through 2009. Results: Among 53,229 NLST subjects (median follow‐up 6.5 years after randomization), the incidence of lung cancer was 615 per 100,000 person‐years (32% of 6142 overall first primary incident invasive cancers), and that of non‐lung cancer was 1327 per 100,000 (68%). Non‐lung cancer incidence exceeded that for lung cancer in all 5‐year age categories and all quintiles of smoking pack‐years. Besides lung cancer, the most common cancers were prostate, breast, colon/rectum, bladder, and head/neck; 23% were smoking‐related cancers, and 54% were cancer types lacking recommended population‐based screening modalities (32% excluding prostate). Non‐lung cancer comprised 48% of 1793 cancer deaths. Conclusions: In the NLST, only 32% of first primary cancer incidence after study entry was lung, compared with 68% non‐lung. Even in a population at high risk for lung cancer, a single‐cancer screening test misses most cancers. Thus, in combination with existing single‐cancer screening modalities, multi‐cancer screening tests—which address many of the incident non‐lung cancers in this trial—have potential to address a currently inaccessible portion of cancer morbidity and mortality. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA plays a critical role in the pathophysiology of cancer. However, the associations between mitochondrial DNA copy number (mtDNA‐CN) and cancer risk are controversial. Mendelian randomization (MR) analyses were performed using three independent instrumental variables (IVs) to explore potential associations between mtDNA‐CN and 20 types of cancer. The three sets of IVs were primarily obtained from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. The outcome data of cancers were investigated using summary statistics from the FinnGen cohort. The potential causal associations were evaluated using the MR‐Egger regression, weighted median, inverse‐variance weighted (IVW), and weighted mode methods. The robustness of IVW estimates was validated using leave‐one‐out sensitivity analysis. Additionally, a meta‐analysis was conducted to pool results from three sets of IVs. The results revealed that genetically predicted mtDNA‐CN was not associated with cancer risk (odds ratio = 1.02; 95% confidence interval: 0.95–1.10). Subgroup analyses indicated no causal association between mtDNA‐CN and breast, lung, prostate, skin, colorectal, gastric, liver, cervical uteri, esophageal, thyroid, bladder, pancreas, kidney, corpus uteri, ovary, brain, larynx, and anus cancers. It was observed that mtDNA‐CN was associated with lip, oral cavity, and testis cancers. However, these results should be interpreted with caution because a small number of patients with lip and oral cavity or testis cancers were included. The comprehensive MR analysis demonstrated that mtDNA‐CN is not a suitable biomarker for tumor risk assessment. [ABSTRACT FROM AUTHOR]

Objective: Due to the inconsistency of the evidence about the cancer risk among patients with schizophrenia, the aim of this study was to analyse cancer mortality and morbidity in patients with schizophrenia treated in a single centre in Lithuania during the study period of 1992–2020. Materials and Methods: A retrospective cohort study was conducted in Vilnius Republican Psychiatric Hospital, the biggest specialised psychiatric hospital in Lithuania, with approximately 5000 hospital admissions annually. The patients' cohort was established by identifying all patients with the diagnosis of schizophrenia (ICD‐10 code F20) in the hospital database from 1 January 1992 until 31 December 2017. The cancer cases and cancer deaths in the cohort were identified in the Lithuanian Cancer Register through linkage procedures. The analysis of risk was based on a comparison of observed and expected numbers of cancers and deaths. Expected number of cancer cases were calculated by multiplication of the exact person‐years under observation in the cohort by sex, calendar year and a 5‐year age‐group‐specific national incidence and mortality rate. All statistical analyses were carried out using STATA 15 statistical software. Results: During the follow‐up, out of 8553 patients, 673 cases of cancer were diagnosed in both sexes. Statistically significantly lower risk for overall cancer incidence was observed in men (SIR 0.74, 95% CI 0.66–0.83), but not in women (SIR 1.07, 95% CI 0.97–1.18). Statistically significant lower overall cancer mortality risk was observed in men (SMR 0.82, 95% CI 0.70–0.96), while in the women's group, risk of cancer deaths was significantly higher compared to the general population (SMR 1.28, 95% CI 1.11–1.48). We observed lower risk for pancreatic cancer (SIR 0.36, 95% CI 0.14–0.96), non‐melanoma skin cancer (SIR 0.54, 95% CI 0.33–0.88) and prostate cancer (SIR 0.69, 95% CI 0.55–0.87) in men and higher risk for malignant neoplasm of liver (SIR 2.58, 95% CI 1.53–4.36) and skin melanoma (SIR 2.03, 95% CI 1.12–3.66) in men and for breast cancer (SIR 1.38, 95% CI 1.14–1.66) and corpus uteri cancer (SIR 1.56, 95% CI 1.18–2.07) in women. Conclusions: The current results of our study indicate lower risk of overall cancer incidence and mortality in male patients with schizophrenia, while female patients had a higher mortality risk, alongside variations in the risk of different cancer types. This information is important not only for patients, but for healthcare specialists to develop effective disease‐specific preventive interventions and programmes. [ABSTRACT FROM AUTHOR]

The immune response–gut microbiota interaction is implicated in various human diseases, including cancer. Identifying the link between the gut microbiota and systemic inflammatory markers and their association with cancer will be important for our understanding of cancer etiology. The current study was performed on 8090 participants from the population‐based Rotterdam study. We found a significant association (false discovery rate [FDR] ≤0.05) between lymphocytes and three gut microbial taxa, namely the family Streptococcaceae, genus Streptococcus, and order Lactobacillales. In addition, we identified 95 gut microbial taxa that were associated with inflammatory markers (p < 0.05). Analyzing the cancer data, we observed a significant association between higher systemic immune‐inflammation index (SII) levels at baseline (hazard ratio (HR): 1.65 [95% confidence interval (CI); 1.10–2.46, p ≤ 0.05]) and a higher count of lymphocytes (HR: 1.38 [95% CI: 1.15–1.65, p ≤ 0.05]) and granulocytes (HR: 1.69 [95% CI: 1.40–2.03, p ≤ 0.05]) with increased risk of lung cancer after adjusting for age, sex, body mass index (BMI), and study cohort. This association was lost for SII and lymphocytes after additional adjustment for smoking (SII = HR:1.46 [95% CI: 0.96–2.22, p = 0.07] and lymphocytes = HR: 1.19 [95% CI: 0.97–1.46, p = 0.08]). In the stratified analysis, higher count of lymphocyte and granulocytes at baseline were associated with an increased risk of lung cancer in smokers after adjusting for age, sex, BMI, and study cohort (HR: 1.33 [95% CI: 1.09–1.62, p ≤0.05] and HR: 1.57 [95% CI: 1.28–1.92, p ≤0.05], respectively). Our study revealed a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, with an increased risk of developing lung cancer. [ABSTRACT FROM AUTHOR]

Aims: Adequate diagnosis of human papillomavirus (HPV)‐associated high‐grade squamous intraepithelial lesion (HSIL) and HPV‐independent vulvar intraepithelial neoplasia (VIN) is essential but can be challenging. We comprehensively characterized a large population‐based series of vulvar lesions, originally reported as high‐grade VIN, and assessed the cancer risk. Methods and results: Baseline high‐grade VIN of 751 patients were categorized by histopathological reassessment, integrating the results of immunohistochemistry (p16INK4a, p53, Ki‐67) and HPV DNA testing. Integrated analyses resulted in 88.4% HPV‐associated lesions (77.0% HSIL, 10.9% low‐grade SIL [LSIL], and 0.4% vulvar squamous cell carcinoma [VSCC]), 10.9% HPV‐independent lesions (6.1% HPV‐independent VIN, 4.7% nondysplastic lesions, and 0.1% VSCC) and 1.1% inconclusive lesions. HSIL demonstrated p16INK4a block‐positivity in 99.0%, increased Ki‐67 in ≥2/3rd of the epithelium in 93.6%, and HPV positivity in 99.6%. In HSIL, a p53 wildtype mid‐epithelial staining pattern was common (51.6%) while this was not observed in HPV‐independent lesions. HPV‐independent VIN harboured mutant p53 patterns in 65.2% and showed a wide morphological spectrum, ranging from differentiated to nondifferentiated ('HPV‐associated‐like', in 41.3%). Kaplan–Meier analyses showed a 10‐year cancer risk of 8.0% in HPV‐associated HSIL, 67.4% in HPV‐independent VIN/p53mutant, and 27.8% in HPV‐independent VIN/p53wildtype. Strikingly, the 10‐year cancer risk was 73.3% in HPV‐independent VIN with nondifferentiated ('HPV‐associated‐like') morphology. Conclusion: Immunohistochemistry by p16INK4a and p53 is highly recommended for optimal categorization into HPV‐associated and HPV‐independent VIN, which is of utmost importance given the different cancer risk. The high cancer risk of HPV‐independent VIN underscores the need for surgical treatment and close follow‐up, especially in case of a p53 mutant pattern and/or nondifferentiated morphology. [ABSTRACT FROM AUTHOR]

The contamination of public water supply and groundwater resources is a major concern in many parts of developing nations. Polluted water poses serious health risks to humans and the environment. This research was conducted to investigate the seasonal variations of the water quality parameters in the public water supply. To assess the supply water quality in different blocks of Ambala District, hydro‐chemical analysis was conducted after a series of systematic sampling in various locations. The statistical tools for water quality indexing including water quality indexing (WQI), heavy metal pollution indexing (HMPI), pollution indexing (PI), overall pollution indexing (OPI), metal indexing (MI), and hazard indexing (HI) were used for data as well as the health hazard analysis through water pathway. Overall, 40 water samples were taken from the public water supply systems covering winter and summer seasons, and the levels of pH, total dissolved solids (TDS), EC, F−, Cl−, NO3−, SO42−, HCO3−, As, B, Cd, Co, Pb, Zn, Cr, Fe, and Mn were investigated. The weight arithmetic index method was used for WQI, and water pollution indices such as HMPI, PI, OPI, and MI were calculated using different models to check the severity of contamination. The mean hazard quotient and hazard index values calculated using the concentration levels of As, B, Cd, Co, Pb, Cr, Fe, Mn, Zn, F−, and NO3− reveal that supply water may pose a significant health risk to both adults and children that further varies with temporal and spatial changes. During both seasons, a high carcinogenic risk for both adults and children was observed in the studied area because of high levels of As, Pb, Cd, and NO3−. Practitioner Points: The quality of public supply water was assessed at the selected sites of Ambala, India.High levels of NO3−, As, Cd, and Pb were observed posing a health risk to adults and children via water pathway.95% of the samples qualified for the excellent water quality category with respect to the levels of F−, Cl−, NO3−, SO42−, HCO3−, pH, EC, and TDS.Statistical analysis (HMPI, PI, MI, OPI, HI) using different models revealed water contamination with reference to the levels of NO3−, As, Pb, Cr, Ni, and Cd.Immediate measures are needed to uphold the safety and health of the natives. [ABSTRACT FROM AUTHOR]

Background/Objectives: Second primary cancers (SPCs) are a leading cause of morbidity and mortality among cancer survivors. In this study, we aimed to characterize the incidence of SPCs among pediatric and young adult survivors of CM. Methods: Using the Surveillance, Epidemiology, and End Results Program data spanning 2000–2018, we calculated standardized incidence ratios (SIR) to assess SPC risk in all pediatric (0–18 years) and young adult (19–29 years) patients with a first primary cancer diagnosis of CM. Results: Of 7,169 total CM survivors, 632 (8.82%) developed a SPC, corresponding to a 5‐fold increased risk (standardized incidence ratio [SIR] 4.98; 95% confidence interval [CI] 4.60–5.38) compared to the general population. There was a highly elevated risk for second primary melanoma across all age groups (SIR 32.5; 95% CI 29.7–35.6), constituting the majority of SPC diagnoses (N = 485). Infants diagnosed with CM before 1 year of age had the highest risk for any SPC (SIR 164; 95% CI 19.8–592) and young adults diagnosed at 25–29 years had the lowest risk (SIR 4.64; 95% CI 4.19–5.13). SPC incidence was highest within the first year of CM diagnosis (SIR 27.5; 95% CI 23.7–31.6) and progressively decreased with time. Conclusions: Variation exists in the incidence and type of SPC according to age among pediatric and young adult survivors of CM. [ABSTRACT FROM AUTHOR]

Tandoori cooking is a popular food preparation method in India involving a unique combination of grilling, baking, barbecuing, and roasting processes. This study determined the levels of 16 polycyclic aromatic hydrocarbons (PAHs) in tandoori chicken and assessed the associated health risk. The sum of 16 PAHs concentration ranged from 25.4 to 3733 μg/kg with an average of 440 ± 853 μg/kg. Analyzed samples demonstrated major contribution of 2, 3, and 4 ring PAHs. Diagnostic ratios identified combustion and high‐temperature processes as the main source favoring PAHs generation in these samples. Benzo(a)pyrene equivalents and incremental lifetime cancer risk (ILCR) estimates for different population groups (boys, girls, adult males, adult females, elderly males, elderly females) associated with dietary intake of these products ranged from 6.88E‐05 to 4.13E‐03 and 1.63E‐08 to 1.72E‐06, respectively. Since the ILCR values fell within the safe limits (1E‐06, i.e., nonsignificant), the consumption of tandoori chicken may be considered as safe. The study emphasizes the need for extensive studies on PAHs formation in tandoori food products. [ABSTRACT FROM AUTHOR]

Aflatoxins (AFs) are hepatotoxic, mutagenic, genotoxic, and immunosuppressive toxins. Several food commodities consumed in the Kingdom of Saudi Arabia (KSA) are susceptible to AF contamination because of improper storage practices and the warm and humid climate of the country. Therefore, the occurrence of AFs in 2388 food samples was measured and the estimated daily intake (EDI) of AFs in Saudi adults was assessed. The risks of AFB1 exposure were characterized using the margin of exposure (MoE) approach and by estimating the number of possible hepatocellular carcinoma (HCC) cases in the KSA. The results revealed that 12.1% of the analyzed samples were contaminated with AFs and the highest concentration of total AFs was observed in the nut and seed group. The mean EDI of AFB1 was estimated to be 0.21 and 0.55 ng/kg body weight (bw)/day for the lower bound (LB) and upper bound (UB) scenarios, respectively. The MoEs were estimated to be 1902.4 and 722.1, while the estimated liver cancer risk ranged from 0.002 to 0.008 cancer cases/year/100,000 persons. Based on the study's findings, contamination with AFs in the KSA is low; however, AFs are considered potent genotoxic contaminants, and therefore, exposure through food should be kept as low as possible. [ABSTRACT FROM AUTHOR]

Aim: Little is known about the association of cancers other than esophageal adenocarcinoma with gastroesophageal reflux disease (GERD). This study aimed to examine the association between GERD and the risk of different types of cancer. Methods: A cohort study was conducted using data from the National Health Screening Cohort. We included 10,261 GERD patients and 30,783 non‐GERD individuals who were matched in a 1:3 ratio by age and sex. All participants were followed‐up until cancer diagnosis, death, or end of the study (December 31, 2015). Hazard ratios were calculated using the Cox proportional hazards model, adjusting for smoking and alcohol consumption, physical activity, body mass index, income, area, and Charlson Comorbidity Index. Results: The median follow‐up time was 9.9 years. GERD was associated with an increased risk of esophageal (adjusted hazard ratios [aHR] = 3.20 [1.89–5.41]), laryngeal (aHR = 5.42 [2.68–10.96]), and thyroid cancers (aHR = 1.91 [1.55–2.34]) after controlling for all covariates. The results were consistent when examining GERD with esophagitis (K210) and without esophagitis (K219) separately. For thyroid cancer, the results were insignificant after controlling for having ever‐received thyroid biopsy procedures. A dose–response relationship was found between GERD and esophageal cancer as well as laryngeal cancer, with patients with a longer duration of GERD treatment showing a stronger effect. In contrast, GERD was associated with a reduced risk of colorectal (aHR = 0.73 [0.59–0.90]), liver (aHR = 0.67 [0.51–0.89]), and pancreatic cancers (aHR = 0.43 [0.24–0.76]), which might have resulted from differences in healthcare utilization between GERD and non‐GERD groups. Conclusion: GERD was associated with an increased risk of esophageal and laryngeal cancers. Additionally, early detection and treatment of precancerous lesions among the GERD group could lead to a lower risk of colorectal, liver, and pancreatic cancers. [ABSTRACT FROM AUTHOR]

Background: The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle‐based guidelines that aim to reduce cancer risk. A systematic review and meta‐analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted. Methods: MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta‐analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1‐point increment) and categorical (highest vs. lowest score category) variable using random‐effects models were estimated. Results: Eighteen studies (11 cohort; seven case‐control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1‐point increment in adherence score was 0.89 (95% CI, 0.85–0.93; I2 = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84–0.91; I2 = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86–0.98, I2 = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta‐analysis results using categorical adherence score variables were consistent with these findings. Conclusions: Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted. PROSPERO registration number: CRD42022313327. Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, lung, and colorectal cancers. Future studies investigating associations with risk of other forms of cancer are warranted. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) widely exist in environmental substrates and are closely related to individual circulating vitamin D levels and tumorigenesis. Therefore, we proposed to evaluate the relationship between PAH exposure, vitamin D, and the risks for 14 cancer types via a causal inference framework underlying the mediation analysis. We evaluated seven urine monohydroxylated PAH (OH‐PAH) and serum vitamin D concentrations of 3306 participants from the National Health and Nutrition Examination Survey between the 2013 and 2016 survey cycles and measured PAH concentrations in 150 subjects from the Nanjing cohort. We observed a significant negative dose–response relationship between increased OH‐PAH levels and vitamin D deficiency. Each unit increase in ∑OH‐PAHs could lead to a decrease in vitamin D levels (βadj = −0.98, Padj = 2.05 × 10−4). Body mass index could have interaction effects with ∑OH‐PAHs and affect vitamin D levels. Coexposure to naphthalene and fluorene metabolites mutually affected vitamin D levels. Notably, vitamin D could causally mediate the relationship between OH‐PAHs and nine types of cancer (e.g., colorectal cancer, liver cancers, etc.). This study first emphasizes the causal cascade of individual OH‐PAHs, vitamin D, and cancer risk, providing insights into prevention via the environment. [ABSTRACT FROM AUTHOR]

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase‐Control (MCC‐Spain) study were recruited (2008‐2013). The consumption of AS, from table‐top sweeteners and artificially sweetened beverages, was assessed through a self‐administered and validated food frequency questionnaire (FFQ). Sex‐specific quartiles among controls were determined to compare moderate consumers (

The association between a family history of breast cancer (FHBC) in female first‐degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site‐specific cancers in men with and without FHBC. A population‐based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age‐matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow‐up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07‐1.70), 1.33 (1.12‐1.56), 1.28 (1.13‐1.44) and 3.03 (1.130‐8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11‐2.57) and increased the risk of thyroid cancer by 3.41‐fold (95% CI: 1.10‐10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation‐related cancer surveillance. [ABSTRACT FROM AUTHOR]

Elevated nickel (Ni) content in soils and water cause a potential threat to food safety and human health. Owing to its numerous uses from common domestic items to industrial usage, it is vital to assess its bioavailability and speciation in the natural environment. In this review, the biogeochemical cycling of Ni in the natural environment and numerous aspects like dissolution, reducing‐oxidizing condition, pH, precipitation, and biological transformations have been briefly discussed. Moreover, health risks associated with Ni have been assessed based on the datasets (soil samples from diverse countries) collected from the literature, and it exerts various health perils in humans for example punctures of the nasal septum, prolonged rhinitis, and contact dermatitis instigated by the absorption of Ni‐metal dust, Ni alloys, and Ni salts on injured skin etc. The carcinogenic and non‐carcinogenic risks inferences showed that dermal interaction is the foremost method of revelation, and children are more susceptible than adults. The findings of this study will be significant for scientists, environmentalists, and policymakers in making strategic strategies for environmental protection and strategic human health management to reduce Ni pollution in the natural environment. [ABSTRACT FROM AUTHOR]

Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven case‐control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B‐cell lymphoma (N cases = 3123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per SD increase of the MS, with and without adjustment for health‐related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR = 1.5‐1.7) with lung cancer risk for smoking MS; moderate associations (RR = 1.2‐1.3) with urothelial cancer risk for smoking MS and with mature B‐cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR = 1.1‐1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B‐cell neoplasms: +8%). Methylation scores for smoking, BMI and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction. What's new? Data from large, population‐based studies have long indicated that lifestyle factors are associated with increased cancer risk. But molecular markers might provide more accurate exposure data than questionnaires, and may also reveal variations in individual responses. In this study, the authors found that DNA methylation scores may provide such a biomarker. They found that changes in methylation associated with smoking, alcohol consumption and obesity are also associated with an increased risk of several types of cancer. These lifestyle methylation scores may thus provide improved risk prediction for these cancers. [ABSTRACT FROM AUTHOR]

Pediatric patients with pulmonary hypertension (PH) receive imaging studies that use ionizing radiation (radiation) such as computed tomography (CT) and cardiac catheterization to guide clinical care. Radiation exposure is associated with increased cancer risk. It is unknown how much radiation pediatric PH patients receive. The objective of this study is to quantify radiation received from imaging and compute associated lifetime cancer risks for pediatric patients with PH. Electronic health records between 2012 and 2022 were reviewed and radiation dose data were extracted. Organ doses were estimated using Monte Carlo modeling. Cancer risks for each patient were calculated from accumulated exposures using National Cancer Institute tools. Two hundred and forty-nine patients with PH comprised the study cohort; 97% of patients had pulmonary arterial hypertension, PH due to left heart disease, or PH due to chronic lung disease. Mean age at the time of the first imaging study was 2.5 years (standard deviation [SD] = 4.9 years). Patients underwent a mean of 12 studies per patient per year, SD = 32. Most (90%) exams were done in children <5 years of age. Radiation from CT and cardiac catheterization accounted for 88% of the total radiation dose received. Cumulative mean effective dose was 19 mSv per patient (SD = 30). Radiation dose exposure resulted in a mean increased estimated lifetime cancer risk of 7.6% (90% uncertainty interval 3.0%-14.2%) in females and 2.8% (1.2%-5.3%) in males. Careful consideration for the need of radiation-based imaging studies is warranted, especially in the youngest of children. [ABSTRACT FROM AUTHOR]

Introduction: Body mass index (BMI) fails to identify up to one‐third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity‐related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess metabolic dysfunction with or without obesity, were evaluated for association with ORC risk. Methods: National Health and Nutrition Examination Survey participants from 1999 to 2018 (N = 19,500) were categorized into phenotypes according to the metabolic syndrome (MetS) criteria and BMI: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Adjusted multivariable logistic regression models were used to evaluate associations with ORC. Results: With metabolic dysfunction defined as ≥1 MetS criteria, ORC cases (n = 528) had higher proportions of MUNW (28.2% vs. 17.4%) and MUO (62.6% vs. 60.9%) phenotypes than cancer‐free individuals (n = 18,972). Compared with MHNW participants, MUNW participants had a 2.2‐times higher ORC risk [OR (95%CI) = 2.21 (1.27–3.85)]. MHO and MUO participants demonstrated a 43% and 56% increased ORC risk, respectively, compared to MHNW, but these did not reach statistical significance [OR (95% CI) = 1.43 (0.46–4.42), 1.56 (0.91–2.67), respectively]. Hyperglycaemia, hypertension and central obesity were all independently associated with higher ORC risk compared to MHNW. Conclusions: MUNW participants have a higher risk of ORC than other abnormal phenotypes, compared with MHNW participants. Incorporating metabolic health measures in addition to assessing BMI may improve ORC risk stratification. Further research on the relationship between metabolic dysfunction and ORC is warranted. [ABSTRACT FROM AUTHOR]

Background: Fish is one of the main sources of food and income in Tanzania, with 25% of the population depending on fishing activities as a source of food, income, and employment. But fish consumers are vulnerable to exposure to toxic pollutants including PCBs due to the lipophilic nature of the pollutants which accumulate in fish. Results: The estimated mean NDL PCBs concentration level was 0.84 ng/g w/w and the mean fish consumption rate among fishermen was 0.4 kg/day. Mean exposure of the fisher- men and fish vendors to total PCBs ranged between 9.62 and 36.12 ng/kg bw/day depend- ing on the estimation scenario (lower bound/upper bound) for both normal and higher fish consumers. The general population exposure to total PCBs was 0.4 and 0.8 ng/kg bw/day in lower-bound and upper-bound estimation scenarios respectively. The estimated lifetime carcinogenic and non-carcinogenic hazard indices from intake of estimated total PCBs by fishermen and fish vendors exceeded the recommended tolerable daily intake, TDI, raising serious concerns for adverse health effects to fishermen and fish vendors. However, for the general population, there was no concern for any potential health effects as the estimated hazard indices were far below the recommended levels for intake of total PCBs. Conclusion: The exposure levels of fishermen and fish vendors to PCBs via consumption of Rastrelliger kanagutra (Indian mackerel) in Dar es Salaam are high enough to course serious health concerns, especially for high fish consumers and efforts should be taken to encourage diversification of fish species intake. [ABSTRACT FROM AUTHOR]

Hereditary hematopoietic malignancies (HHMs) are inherited syndromes that confer the risk of blood cancer development. With the rapid acceleration of next‐generation sequencing (NGS) into commercial biotechnology markets, HHMs are increasingly recognized by genetic counselors and clinicians. In 2020, it was demonstrated that most diagnostic test offerings for HHMs were insufficient for accurate diagnosis, failing to sequence the full spectrum of genetic events known to cause HHMs. We hypothesized the number of genes on commercially available HHM assay increased from 2020 to 2022, consistent with a more comprehensive sequencing approach. Here, we analyzed assays from eight commercial laboratories to determine the HHM‐related genes sequenced by these assays. We compared these assays with panels from 2020 to determine trends in sequencing quality. Most HHM diagnostic assays did not change and remain insensitive for the detection of all HHM‐related variants. Most (75%) HHM assays do not sequence CHEK2, the gene most frequently mutated in HHMs, and 25% of HHM assays does not sequence DDX41, the second most frequent HHM driver. The quality of HHM diagnostic assays stagnated despite the discovery of novel HHM‐related genes and prior work demonstrating heterogeneity in the quality of HHM testing. Most commercially available HHM tests remain insufficient. [ABSTRACT FROM AUTHOR]

Background: Approximately 90% of pancreatic ductal adenocarcinoma (PDAC) cases are driven by the untargetable non-G12C KRAS mutations, and only a small subset of patients are eligible for FDA-approved precision therapies. The practice of precision therapy in pancreatic cancer was limited by the paucity of targetable genetic alterations, especially in the Asian population. Methods: To explore therapeutic targets in 499 Chinese PDAC patients, a deep sequencing panel (OncoPanscan™, Genetron health) was used to characterize somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants. Results: We performed genomic profiling in 499 Chinese PDAC patients, which revealed somatic driver mutations in KRAS, TP53, CDKN2A, SMAD4, ARID1A, RNF43, and pathogenic germline variants (PGVs) in cancer predisposition genes including BRCA2, PALB2, and ATM. Overall, 20.4% of patients had targetable genomic alterations. About 8.4% of patients carried inactivating germline and somatic variants in BRCA1/2 and PALB2, which were susceptible to platinum and PARP inhibitors therapy. Patients with KRAS wild-type disease and early-onset pancreatic cancer (EOPC) harbored actionable mutations including BRAF, EGFR, ERBB2, and MAP2K1/2. Compared to PGV-negative patients, PGV-positive patients were younger and more likely to have a family history of cancer. Furthermore, PGVs in PALB2, BRCA2, and ATM were associated with high PDAC risk in the Chinese population. Conclusions: Our results demonstrated that a genetic screen of actionable genomic variants could facilitate precision therapy and cancer risk reduction in pancreatic cancer patients of Asian ethnicity. [ABSTRACT FROM AUTHOR]

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow‐up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3‐2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4‐5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5‐5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3‐2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2‐2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9‐4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics. [ABSTRACT FROM AUTHOR]

Police work may expose officers to various circumstances that have potential for increasing their risk of cancer, including traffic‐related air pollution, night shift work and radiation from radars. In this study, we examined the incidence of cancer among Nordic male and female police officers. We utilize data from the Nordic Occupational Cancer (NOCCA) project, which linked census data on occupations from Finland, Iceland, Norway and Sweden to national cancer registries for the period 1961 to 2005. We report standardized incidence ratios (SIR) and 95% confidence intervals (CI) of selected cancers for each country by sex, age and calendar period. The cohort included 38 523 male and 1998 female police officers. As compared with the general population, male police officers had a 7% (95% CI: 4‐9%) excess cancer risk, with elevated SIRs for various cancer sites, including prostate (SIR 1.19, 1.14‐1.25), breast (SIR 1.77, 1.05‐2.80), colon (SIR 1.22, 1.12‐1.32) and skin melanoma (SIR 1.44, 1.28‐1.60). Conversely, male police officers had a lower risk of lung cancer than the general population (SIR 0.72, 0.66‐0.77). In female police officers, the SIR for cancer overall was 1.15 (0.98‐1.34), and there was a slight excess of cancers of the breast (SIR 1.25, 0.97‐1.59) and colon (SIR 1.21, 0.55‐2.30). In conclusion, cancer incidence among the police officers was slightly higher than in the general population. Notably, SIRs were elevated for cancer sites potentially related to night shift work, namely colon, breast and prostate cancer. [ABSTRACT FROM AUTHOR]

Introduction: The long‐term risk of cancer among first‐degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers. Material and methods: Using registry data, we conducted a retrospective cohort study with a total of 6501 first‐degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach). Results: The overall number of cancers was not increased among the first‐degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27–2.79), mostly explained by a 2.30‐fold (95% CI 1.46–3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient. Conclusions: In our study cohort, we did not observe an increase in the overall cancer risk among the first‐degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives. [ABSTRACT FROM AUTHOR]

Fuzzy‐trace theory predicts that decisionmakers process numerical information about risk at multiple levels in parallel: the simplest level, nominal (categorical some‐none) gist, and at more fine‐grained levels, involving relative comparison (ordinal less‐more gist) and exact quantities (verbatim representations). However, little is known about how individual differences in these numerical representations relate to judgments and decisions, especially involving health tradeoffs and relative risks. To investigate these differences, we administered measures of categorical and ordinal gist representations of number, objective numeracy, and intelligence in two studies (Ns = 978 and 956). In both studies, categorical and ordinal gist representations of number predicted risk judgments and decisions beyond objective numeracy and intelligence. Participants with higher scores in categorical gist were more likely to choose options to avoid cancer recurrence risks; those who were higher in ordinal gist of numbers were more likely to discriminate relative risk of skin cancer; and those with higher scores in objective numeracy were more likely to choose options that were numerically superior overall in terms of relative risk of skin cancer and of genetic risks of breast cancer (e.g., lower numerical probability of cancer). Results support parallel‐processing models that assume multiple representations of numerical information about risk, which vary in precision, and illustrate how individual differences in numerical representations are relevant to tradeoffs and risk comparisons in health decisions. These representations cannot be reduced to one another and explain psychological variations in risk processing that go beyond low versus high levels of objective numeracy. [ABSTRACT FROM AUTHOR]

We report a series of four unrelated adults with Smith–Magenis syndrome (SMS) and concomitant features of Birt–Hogg–Dubé (BHD) syndrome based upon haploinsufficiency for FLCN and characteristic renal cell carcinomas and/or evidence of cutaneous fibrofolliculomas. Three of the cases constitute the first known association of histopathologically verified characteristic BHD‐associated renal tumors in adults with SMS; the fourth was identified to have histologically confirmed skin fibrofolliculomas. Molecular analysis documented second‐hit FLCN mutations in two of the three cases with confirmed BHD renal pathology. These cases suggest the need to expand management recommendations for SMS to include kidney cancer surveillance starting at 20 years of age, as per the screening recommendations for BHD syndrome. [ABSTRACT FROM AUTHOR]

Background: Prevention and early intervention can improve survival and quality of life across all cancers. Patient understanding of risk factors and associated actionable lifestyle changes and screening programs is not well understood by clinicians Methods: An Internet‐based tool, Reduce My Risk, was created in 2009 and made available on oncolink.org. Users voluntarily completed a survey regarding demographics and cancer risk factors, and received information about their cancer risk Results: Twenty eight thousand and one surveys were completed from 2009 to 2019. Median age was 26 years (18–101); 60% were females, 87% lived in North America, and 37% had at least a bachelor's degree. Users reported on behavioral/ modifiable risk factors: 13% were current smokers, 52% were current consumers of alcohol, and 8% of those had ≥14 drinks/week. Body mass index (BMI) was ≥30 in 19%; 74% of all surveys reported dietary risks and 36% reported infrequent exercise. Excess UV exposure was reported by 19%. Among women, 36% reported performing breast self‐examinations monthly, and 50% reported receiving clinician breast examinations at least once every 3 years. Sixty seven percent of men 55–75 years reported screening prostate specific antigen testing, with 50% receiving annual digital rectal examinations. Nonmodifiable risk factors included family cancer history (64%), genetic syndrome (3%), and cancer‐predisposing health conditions (26%) Conclusions: Ninety‐seven percent of users reported modifiable risk factors, and 60% reported ≥4 of these risk factors. Understanding detailed characteristics of a large number of respondents has the potential to improve educational interventions to reduce cancer risk through behavioral modification and cancer screening across the general public. [ABSTRACT FROM AUTHOR]

Objective: Ashkenazi‐Jewish (AJ) population‐based BRCA testing is acceptable, cost‐effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long‐term results of population‐based BRCA testing on lifestyle behaviour and cancer risk perception. Design: Two‐arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population‐screening (PS); (b) family history (FH)/clinical criteria testing. Setting North London AJ‐population. Population/Sample: AJ women/men >18 years. Exclusions: prior BRCA testing or first‐degree relatives of BRCA‐carriers. Methods: Participants were recruited through self‐referral. All participants received informed pre‐test genetic counselling. The intervention included genetic testing for three AJ BRCA‐mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1‐year/2‐year/3‐year follow‐ups. Generalised linear‐mixed models adjusted for covariates and appropriate contrast tests were used for between‐group/within‐group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P < 0.0039 considered significant. Outcome measures: Lifestyle/behavioural outcomes at baseline/1‐year/2‐year/3‐year follow‐ups. Results: 1034 participants were randomised to PS (n = 530) or FH (n = 504) arms. No significant difference was identified between PS‐ and FH‐based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA‐negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P < 0.001). Conclusion: Population‐based and FH‐based AJ BRCA testing have similar long‐term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception. Jewish Pop BRCA testing increases vitamin use and has similar lifestyle impact as FH testing on diet, exercise, alcohol, breast screening. [ABSTRACT FROM AUTHOR]

Background: The relationship of tissue chemistry to breast density and cancer risk has not been documented despite breast density being a known risk factor. Purpose: To investigate whether distinct chemical profiles associated with breast density and cancer risk are identified in healthy breast tissue using in vivo two‐dimensional correlated spectroscopy (2D COSY). Study Type: Prospective. Population: One‐hundred‐seven participants including 55 at low risk and 52 at high risk of developing breast cancer. Field Strength/Sequence: 3 T/ axial/ T1, T2, 2D COSY. Assessment Two radiologists defined breast density on T2. Interobserver variability assessed. Peak volumes normalized to methylene at (1.30, 1.30) ppm as internal shift reference. Statistical Tests: Chi‐squared/Mann–Whitney/Kappa statistics/Kruskal Wallis/pairwise analyses. Significance level 0.05. Results: Ten percentage were fatty breasts, 39% scattered fibroglandular, 35% heterogeneously dense, and 16% extremely dense. Interobserver variability was excellent (kappa = 0.817). Sixty percentage (64/107) were premenopausal. Four distinct tissue chemistry categories were identified: low‐density (LD)/premenopausal, high‐density (HD)/premenopausal, LD/postmenopausal, and HD/postmenopausal. Compared to LD, HD breast chemistry showed significant increases of cholesterol (235%) and lipid unsaturation (33%). In the low‐risk category, postmenopausal women with dense breasts recorded the largest significant changes including cholesterol methyl 540%, lipid unsaturation 207%, glutamine/glutamate 900%, and choline/phosphocholine 800%. In the high‐risk cohort, premenopausal women with HD recorded a more active chemical profile with significant increases in choline/phosphocholine 1100%, taurine/glucose 550% and cholesterol sterol 250%. Data Conclusion: Four distinct chemical profiles were identified in healthy breast tissue based on breast density and menopausal status in participants at low and high risk. Gradual increase in neutral lipid content and metabolites was noted in both risk groups across categories in different order. In low risk, the HD postmenopausal category exhibited the highest metabolic activity, while women at high risk exhibited the highest lipid content and metabolic activity in the HD premenopausal category. Level of Evidence: 2 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

Background: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI).Methods: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking.Results: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification.Conclusions: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality.Lay Summary: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers. [ABSTRACT FROM AUTHOR]

Aim: The COLO‐COHORT study aims to produce a multi‐factorial risk prediction model for colorectal neoplasia that can be used to target colonoscopy to those at greatest risk of colorectal neoplasia, ensuring that people are not investigated unnecessarily and maximizing the use of limited endoscopy resources. The study will also explore the link between neoplasia and the human gut microbiome. Additionally, the study aims to generate a cohort of colonoscopy patients who are 'research ready' through the development of a consent‐for‐contact (C4C) platform, to facilitate a range of colorectal cancer prevention studies to be conducted at scale and speed. Methods and analysis: This is a multi‐centre observational study involving sites across the UK. Recruitment is over a 6‐year period (2019–2025). Patients recruited to the study are those attending for colonoscopy. Patients are recruited into two groups, namely observational group A (10 000 patients) and C4C group B (10 000 patients), known as COLO‐SPEED (Colorectal Cancer Screening Prevention Endoscopy and Early Diagnosis; https://colospeed.uk). Patients complete a health questionnaire, provide anthropometric measurements and submit biosamples (blood and stool—depending on the part of the study they are recruited into). Patients' colonoscopy and histology findings are also recorded. Models of factors associated with the presence of neoplasia at colonoscopy will be developed using logistic or multinomial regression. For internal validation, model discrimination and calibration will be assessed and bootstrapping and cross‐validation approaches used. To enable long‐term follow‐up for outcomes related to colorectal cancer and polyps, patients are asked to consent to follow‐up through data linkage with national databases. Dissemination: In keeping with good research practice, following analysis by the study team the study investigators will make the anonymized dataset available to other researchers. The C4C platform will also be accessible to other researchers. The study findings will be submitted for publication in peer‐reviewed journals and lay summaries will be disseminated to participants and the wider public. [ABSTRACT FROM AUTHOR]

Background: Ion beam therapy allows for substantial sparing of normal tissues. Besides deterministic normal‐tissue complications, stochastic long‐term effects like secondary cancer (SC) induction are of importance when comparing different treatment modalities. Purpose: To develop a modeling approach for comparison of SC risk in proton and carbon ion therapy. Methods and Materials: The local effect model (LEM) is used to predict the relative biological effectiveness (RBE) of SC induction after particle therapy. A key feature of the new approach is the double use of the LEM, reflecting the competition between the two processes of mutation induction (leading to cancer development) and cell inactivation (leading to suppression of cancer development). Based on previous investigations, treatment plans were in this work analyzed for an idealized geometry in order to assess the underlying systematic dependencies of cancer induction. In a further step, relative SC risks were predicted for proton and carbon ion treatment plans prepared for 10 prostate cancer patients. Results: We investigated the impact of factors such as treatment plan geometry, fractionation scheme, and tissue radiosensitivity to photon irradiation on the ion beam SC risk. Our model studies do not result in a clear preference for either protons or carbon ions, but rather indicate a complex interplay of different aspects. Reduced lateral scattering leads to a lower SC risk for carbon ions compared to protons at the lateral field margins in the entrance channel, while an increased risk was found closely behind the tumor due to projectile fragmentation. The fractionation scheme had little impact on the expected risk ratio. With respect to sensitivity parameters, those characterizing RBE for cell killing of potentially cancerous cells as well as of the primary tumor had the most significant impact. The observed general systematic dependencies are in agreement with results from previous model studies. The prostate patient study reveals reduced SC risks predictions for skin and bones for carbon ions as compared to protons, but higher mean risks for bladder and rectum. Conclusion: The methods established in this work provide a basis for further investigating treatment optimizing strategies for ion beam therapy with regard to SC risk comparisons. [ABSTRACT FROM AUTHOR]

Simpson-Golabi-Behmel syndrome (SGBS) is a rare congenital overgrowth condition characterized by macrosomia, macroglossia, coarse facial features, and development delays. It is caused by pathogenic variants in the GPC3 gene on chromosome Xq26.2. Here, we performed a comprehensive literature review and phenotyping of known patients with molecularly confirmed SGBS and reviewed a novel cohort of 22 patients. Using these data, we characterized the tumor risk for Wilms tumor and hepatoblastoma to suggest appropriate screening for this patient population. In addition, we discuss the phenotypic overlap between SGBS and Beckwith-Wiedemann Spectrum., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Sex differences play a relevant role in cancer susceptibility, incidence and survival. Exploring such differences is difficult because of the close interplay of genetic, epigenetic and hormonal factors. However, a better understanding of the role of such disparities in cancer mechanisms could improve its prevention and therapy. Our study explores how sex differences in pediatric outcomes vary after undergoing first and advanced‐line therapy for hematological malignancies. The primary goal was to evaluate if sex differences in pediatric outcomes after first‐line therapy persist after allogeneic hematopoietic stem cell transplantation (HSCT). The secondary goal was to analyze sex differences in disease risk at onset and pediatric outcomes after first‐line therapy to compare our results with the literature's reported results. Among a total of 485 patients (280 males, 205 females) admitted for hematological malignancies, disease risk at the onset was significantly higher in males (P <.05). One hundred and seventy‐four patients (111 males and 63 females) had a high‐risk disease requiring HSCT. Before HSCT, all patients underwent myeloablative conditioning, which substantially impaired gonadal function. Although the number of boys undergoing HSCT was almost double that of girls, there were no sex‐related differences in overall survival, cancer relapse and complications after HSCT exposure (P >.05). These findings suggest that the existing sex differences in cancer risk ab initio can be somehow flattened by a conditioning regimen, shedding new light on the role of hormonal factors in cancer mechanism and management. [ABSTRACT FROM AUTHOR]

We examined associations between sex‐specific alcohol intake trajectories and alcohol‐related cancer risk using data from 22 756 women and 15 701 men aged 40 to 69 years at baseline in the Melbourne Collaborative Cohort Study. Alcohol intake for 10‐year periods from age 20 until the decade encompassing recruitment, calculated using recalled beverage‐specific frequency and quantity, was used to estimate group‐based sex‐specific intake trajectories. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for primary invasive alcohol‐related cancer (upper aerodigestive tract, breast, liver and colorectum). Three distinct alcohol intake trajectories for women (lifetime abstention, stable light, increasing moderate) and six for men (lifetime abstention, stable light, stable moderate, increasing heavy, early decreasing heavy, late decreasing heavy) were identified. 2303 incident alcohol‐related cancers were diagnosed during 485 525 person‐years in women and 789 during 303 218 person‐years in men. For men, compared with lifetime abstention, heavy intake (mean ≥ 60 g/day) at age 20 to 39 followed by either an early (from age 40 to 49) (early decreasing heavy; HR = 1.75, 95% CI: 1.25‐2.44) or late decrease (from age 60 to 69) (late decreasing heavy; HR = 1.94, 95% CI: 1.28‐2.93), and moderate intake (mean <60 g/day) at age 20 to 39 increasing to heavy intake in middle‐age (increasing heavy; HR = 1.45, 95% CI: 1.06‐1.97) were associated with increased risk of alcohol‐related cancer. For women, compared with lifetime abstention, increasing intake from age 20 (increasing moderate) was associated with increased alcohol‐related cancer risk (HR = 1.25, 95% CI: 1.06‐1.48). Similar associations were observed for colorectal (men) and breast cancer. Heavy drinking during early adulthood might increase cancer risk later in life. [ABSTRACT FROM AUTHOR]

In Ashkenazi Jews (AJ) three recurring pathogenic sequence variants (PSVs) are detected in ~2.5% of the general population in the BRCA1 (c.68_69del = 185delAG, c.5266dup = 5382insC), and BRCA2 (c.5946del = 6174delT). Population‐based screening for these PSVs in AJ women is part of the health basket in Israel. To assess the feasibility and outcome of BRCA genotyping in the Jewish population of Uruguay, AJ in the greater Montevideo area were recruited using ethically approved protocol and without pretest counseling were genotyped for the three predominant AJ PSVs in the BRCA genes. Independently confirmed PSV carriers were counseled, and genetic testing was offered to additional family members. Overall, 327 participants were enrolled: 312 (95%) female, 261 (80%) had all four grandparents AJ, and 14 (4%) women were breast cancer survivors with a mean age ± standard deviation (SD) 50 ± 11.5 years. The BRCA1 c.68_69del PSV was detected in three cancer free participants (0.92%, CI 95% 0.31–2.6), all with a suggestive family history. No carriers of the other two recurrent PSVs were detected. Online oncogenetic counseling was provided for all carriers. In conclusion, the rate of the BRCA1 c.68_69del PSV was similar with the rate in other AJ communities. AJ population BRCA genotyping screens in Uruguay seem feasible and should be promoted. [ABSTRACT FROM AUTHOR]

Cancer is a significant cause of morbidity and mortality after solid organ transplantation (SOT) and related to lifelong immunosuppression. This retrospective registry study assessed for the first time in Finland population‐based cancer risk and cancer mortality after all SOTs (lung and childhood transplantations included) as standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs). Data from transplant registries were linked with the data of Finnish Cancer Registry and Statistics Finland. We followed 6548 consecutive first SOT recipients from 1 January 1987 to 31 December 2016 translating to 66 741 person‐years (median follow‐up time 8.9 years [interquartile range 4.0‐15.1]). In total, 2096 cancers were found in 1483 patients (23% of all patients). Majority of cancers (53%) were nonmelanoma skin cancers (NMSCs). The overall SIR was 3.6 (95% confidence interval [CI]: 3.5‐3.8) and the SIR excluding NMSCs was 2.2 (95% CI: 2.0‐2.3). SIR for all cancers was highest for heart (5.0) and lowest for liver (2.7) recipients. Most common cancer types after NMSCs were non‐Hodgkin lymphoma (NHL), SIR 9.9 (95% CI: 8.5‐11.4) and kidney cancer, SIR 7.3 (95% CI: 6.0‐8.8). Cancer‐related deaths were 17% (n = 408) of all deaths after first month post transplantation. SMR for all cancers was 2.5 (95% CI: 2.2‐2.7) and for NHL 13.6 (95% CI: 10.7‐16.8). Notably, overall SIR for cancer was lower in later period (2000‐2016), 3.0 (95% CI: 2.8‐3.2), than in earlier period (1987‐1999), 4.3 (95% CI: 4.0‐4.5), P <.001. Decrease in cancer incidence was temporally associated with major changes in immunosuppression in the 2000s. [ABSTRACT FROM AUTHOR]

Arsenic is a toxic carcinogen mostly found in subsurface environments. It is released into groundwater mostly via natural geological and hydrological processes. Consumption of such contaminated water leads to serious health crises for mankind. Developing countries in South Asia, particularly the rural regions, have been severely affected by this environmental phenomenon. In India, government authorities have implemented several remedial measures to provide safe drinking water to the rural habitations, ranging from utilization of surface water bodies (e.g., rivers, ponds, etc.) for piped water supply schemes and establishment of groundwater treatment units. This article attempts to review the scientific literature describing the critical situation in India's fourth most populous state of West Bengal and the engineering advances made in the mitigation. The issue of safe disposal or stabilization of arsenic wastewaters generated from the treatment units is often not emphasized in policy discussions. In a concluding note, this article proposes innovations necessary for achieving effective arsenic mitigation in the region that involve both groundwater remediation and waste management in tandem for sustainability. [ABSTRACT FROM AUTHOR]

Whether regular fish oil supplementation is associated with cancer risk is controversial. We aimed to evaluate the association of fish oil supplementation on cancer risk according to fatty fish consumption patterns. From the UK Biobank cohort, 470 804 participants with fish oil supplementation data were included. A total of 147 316 individuals with fish oil supplementation were in the exposed group; the other 323 488 were in the unexposed group. No association was found between self‐report regular fish oil supplementation and overall cancer risk (hazard ratio [HR] = 0.97, 95% confidence intervals [CIs] = 0.95‐1). Stratified by fatty fish consumption level, we found the association between fish oil supplementation and lower cancer risk in participants who consumed fatty fish less than two times per week, with association noted for both overall cancer (HR = 0.96, 95% CI = 0.94‐0.99) and some specific cancers (colon cancer: HR = 0.84, 95% CI = 0.75‐0.94; hepatobiliary cancer: HR = 0.74, 95% CI = 0.58‐0.96; lung cancer: HR = 0.87, 95% CI = 0.78‐0.98). On the contrary, a higher risk of breast cancer was observed (HR = 1.16, 95% CI = 1.01‐1.32) in participants who consumed fatty fish at least two times per week. In conclusion, our findings underscore the need to refine recommendations for nutritional supplements according to inherent diet habits. What's new? Previous evidence from randomised controlled trials and meta‐analyses suggests that fish oil supplementation may not lower overall cancer risk, but the results were largely inconsistent. This large‐scale prospective real‐world analysis of half a million U.K. Biobank participants found that regular fish oil supplementation was not associated with overall cancer risk. When stratifying the participants based on their dietary fish oil consumption, however, regular fish oil supplementation was associated with lower cancer incidence in participants with insufficient dietary fish oil consumption. These findings underscore the need to refine recommendations for fish oil supplementation according to dietary habits. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common cancers causing death worldwide. Many long noncoding RNAs (lncRNAs) have possible carcinogenic or tumor suppressor functions. Some lncRNA polymorphisms are useful for predicting cancer risk, and may help advance personalized therapy management. While the use of lncRNAs as biomarkers is promising, there are still drawbacks, and further studies are needed to verify the consistency of current outcomes in large‐scale populations and different ethnicities. Single nucleotide polymorphisms (SNPs) can disrupt a lncRNAs' function, thus enhancing or hindering disease occurrence. SNPs can directly influence the lncRNA expression by interfering with transcription factor binding or affecting indirectly a regulatory factors' expression. Moreover, the association between lncRNAs and other RNAs or proteins may be disrupted by SNPs. This research sought to assess the association between lncRNA polymorphisms and CRC risk, as well as clinical and therapeutic consequences in certain cases. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS), Lynch‐like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk‐adapted surveillance policies in LS, LLS and FCCX. What's new? While associations between colorectal cancer (CRC) risk and Lynch syndrome (LS) are well‐described, less is known about CRC risks linked to the closely related Lynch‐like syndrome (LLS) and familial colorectal cancer type X (FCCX). In this prospective follow‐up study of patients with LS, LLS, and FCCX, risks were similar for colorectal adenomas but considerably different for first and metachronous CRCs. In addition, LS females who carried MSH2 mutations had notably higher CRC risks than female MLH1 mutation carriers. The identification of variations in carcinogenic pathways between LS, LLS, and FCCX could enable risk‐adapted CRC surveillance for these syndromes. [ABSTRACT FROM AUTHOR]

Background: Effective screening can prevent cervical cancer, but many women choose not to attend their screening tests. Objective: This study aimed to investigate behavioural influences on cervical screening participation using the Theoretical Domains Framework (TDF) and COM‐B models of behaviour change. Design: A qualitative study and semistructured phone interviews were conducted with women invited for routine screening tests within the national cervical screening programme in Ireland. Setting and Participants: Forty‐eight women aged 25–65 years were recruited from the national screening register. Results: Seven core themes were identified that mapped to three COM‐B components and 11 TDF domains: (1) knowledge of cervical cancer and screening, (2) coping with smear tests, (3) competing motivational processes—automatic and reflective, (4) cognitive resources, (5) role of social support, (6) environmental influences and (7) perceputal and practical influences. A range of knowledge about screening, perceived risk of cervical cancer and human papillomavirus infection was evident. Factors that influenced screening behaviours may be hierarchical—some were assigned greater importance than others. Positive screening behaviours were linked to autonomous motivation. Deficits in physical and psychological capability (inadequate coping skills) were barriers to screening, while physical and social opportunity (e.g. healthcare professional 'champions') could facilitate participation. Older women raised age‐related issues (e.g. screening no longer necessary) and had more negative attitudes to screening, while younger women identified practical barriers. Conclusions: This study provides insight into screening participation and will aid development of theoretically informed interventions to increase uptake. Patient or Public Contribution: Women invited for screening tests through the national screening programme were interviewed. A Public & Patient Involvement (PPI) Panel, established to provide input into all CERVIVA research projects, advised the research team on recruitment materials and were given the opportunity to review and comment on the interview topic guide. This panel is made up of six women with various cervical screening histories and experiences. [ABSTRACT FROM AUTHOR]

Objectives: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking‐related, and alcohol‐related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. Methods: The psychosocial factors and cancer incidence (PSY‐CA) consortium was established involving experts in the field of (psycho‐)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two‐stage individual participant data (IPD) meta‐analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta‐analyses will be performed on the risk estimates (stage 2). Conclusion: PSY‐CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta‐analyses. Psychosocial factors and cancer incidence (PSY‐CA) consortium endeavor to understand the role of several different psychosocial factors—including depression and anxiety—in the onset of cancer. The study will employ the use of individual participant data meta‐analyses, combining results from several large, international cohorts with longitudinal designs. Furthermore, PSY‐CA aims to elucidate the role of health behaviors in the relationship between psychosocial factors and cancer risk. [ABSTRACT FROM AUTHOR]

Background: Oral cancer is typically related to environmental carcinogen exposure including tobacco and alcohol. Other less investigated risk factors may be related to a suppressed or dysregulated immune state, and in oral cancer, various levels of immune dysregulation have been found to affect survival and recurrence rates. The rationale for this systematic review was to investigate the possible role that a growing chronic host condition like an autoimmune disease may play in this disease. Methods: A systematic search of the literature was carried out using four electronic databases in order to identify original research of any analytic study design type that investigated the relationship between autoimmune disease and oral cancer. Out of 1,947 identified records, 24 observational studies were included for qualitative synthesis. Results: The studies varied in end points ranging from overall survival (OS), standardized incidence ratio (SIR), and hazard ratio (HR). Due to the heterogenous sampling of studies even within the same study design group, a meta‐analysis was not employed. The current state of the literature is varied and heterogenous in both study design and endpoints. Conclusion: Major limitations existed introducing significant bias especially in determining cancer risk such as lack of information surrounding known etiologic risk factors such as alcohol and tobacco consumption. Despite these limitations, a signal was seen between autoimmune disease and oral cancer outcomes and risk. Future studies investigating the relationship between autoimmune disease and oral cancer in a more focused and quantitative manner are therefore needed. [ABSTRACT FROM AUTHOR]