The association between glyphosate use and mosaic loss of chromosome Y in buccal samples among male pesticide applicators in the Agricultural Health Study.

Glyphosate-based herbicides are the most widely applied pesticides worldwide and have been implicated in the development of certain hematologic malignancies; however, the underlying biological mechanisms are not well-understood. High lifetime use of glyphosate-based herbicides, hereafter referred to as glyphosate, was previously associated with mosaic loss of chromosome Y (mLOY), a biomarker of genomic instability potentially linked to cancer and immune dysregulation, in circulating blood of male farmers from a subcohort of the Agricultural Health Study (AHS). Here, we further investigated the association between glyphosate use and mLOY using buccal-derived DNA among 1,868 male pesticide applicators in an independent AHS study.

Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.

Genomic Characterization of Lung Cancer in Never-Smokers Using Deep Learning.

Despite promising results in using deep learning to infer genetic features from histological whole-slide images (WSIs), no prior studies have specifically applied these methods to lung adenocarcinomas from subjects who have never smoked tobacco (NS-LUAD) - a molecularly and histologically distinct subset of lung cancer. Existing models have focused on LUAD from predominantly smoker populations, with limited molecular scope and variable performance. Here, we propose a customized deep convolutional neural network based on ResNet50 architecture, optimized for multilabel classification for NS-LUAD, enabling simultaneous prediction of 16 molecular alterations from a single H&E-stained WSI.

Pre-diagnostic serum concentrations of free light chains and risk of non-Hodgkin lymphoma in a population-based prospective study.

Elevated serum free light chains (sFLC) indicate immune stimulation and have been associated with increased risk of AIDS-related non-Hodgkin lymphoma (NHL) and post-transplant lymphoproliferative disorder. This study examined 292 incident NHL cases and individually matched controls using pre-diagnostic samples from the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Higher κ (p < 0.

Overview of historical formaldehyde occupational exposure in China.

Objectives: Formaldehyde is a known human carcinogen related to leukemia and nasopharyngeal cancer. As China is the world's largest producer and consumer of formaldehyde, occupational exposure to formaldehyde may pose potential health risks to workers. We aimed to describe occupational exposure to formaldehyde over time in China.

The mutagenic forces shaping the genomes of lung cancer in never smokers.

Lung cancer in never smokers (LCINS) accounts for around 25% of all lung cancers and has been associated with exposure to second-hand tobacco smoke and air pollution in observational studies. Here we use data from the Sherlock-Lung study to evaluate mutagenic exposures in LCINS by examining the cancer genomes of 871 treatment-naive individuals with lung cancer who had never smoked, from 28 geographical locations. KRAS mutations were 3.

Urinary metabolites in association with kidney cancer risk.

Kidney cancer incidence has increased worldwide in recent decades. While metabolomic studies have shown promise in unveiling mechanisms underlying disease development, few studies have investigated prediagnostic urinary metabolites and kidney cancer risk. We conducted a case-control study nested within the Shanghai Women's and Men's Health Studies to prospectively investigate the association between urinary metabolites and kidney cancer risk to understand its etiology and the underlying biological mechanisms.

Lifetime water arsenic, genetic susceptibility, and bladder cancer in the New England Bladder Cancer Study.

Background: Exposure to arsenic in drinking water may interact with common genetic variants in urinary bladder cancer risk.

Methods: We conducted a gene-environment interaction analysis among 1091 bladder cancer cases and 928 controls from the New England Bladder Cancer Study. Genetic variants tested as effect modifiers included those associated with bladder cancer and arsenic metabolism.

Examining the Role of Extrachromosomal DNA in 1,216 Lung Cancers.

The role of extrachromosomal DNA (ecDNA) in lung cancer, particularly in subjects who never smoked (LCINS), remains unclear. Examination of 1,216 whole-genome-sequenced lung cancers identified ecDNA in 18.9% of patients.

Association Between Cardiometabolic Multimorbidity and 15-year Mortality in the Asia Cohort Consortium.

Background: Studies on the association between multimorbidity and mortality in large populations have mainly been conducted in European and North American populations. This study aimed to identify the association between cardiometabolic multimorbidity and all-cause and cardiovascular disease (CVD) mortality in the Asia Cohort Consortium.

Methods: In this prospective cohort study, pooled analysis was performed to evaluate the association between cardiometabolic diseases (hypertension, diabetes, ischemic heart disease, and stroke), multimorbidity, and all-cause and CVD mortality, including premature mortality, among participants from 11 Asian cohort studies.

Epigenome-wide association study of household air pollution exposure in an area with high lung cancer incidence.

Background: Lung cancer incidence among never-smoking women in Xuanwei, China, ranks among the highest worldwide and is largely attributed to household air pollution (HAP) from smoky (bituminous) coal combustion, with early-life exposures possibly playing a critical role. We conducted an epigenome-wide DNA methylation (DNAm) analysis across multiple exposure windows to elucidate molecular mechanisms.

Methods: Leukocyte DNAm was measured in 106 never-smoking women (23 with repeated measurements).

HSA Adductomics in the Shanghai Women's Health Study Links Lung Cancer in Never-Smokers with Air Pollution, Redox Biology, and One-Carbon Metabolism.

Nearly one fourth of lung cancers occur among never-smokers and are predominately lung adenocarcinomas (LUADs) that are distinct from smoking-related cancers. Causal links between LUADs in never-smokers have been attributed to reactive oxygen species (ROS) arising from airborne fine particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs). These effects are pronounced among East Asian women who experience massive exposures to PM and PAHs and have the highest incidence of LUADs in the world.

Organochlorine pesticide use and mosaic loss of chromosome Y in a study of male farmers.

Background: Organochlorine (OC) insecticides are a class of environmentally persistent chemicals linked to risk of several cancers, including non-Hodgkin lymphoma and prostate cancer. In vitro and animal studies suggest some OCs may be genotoxic, but evidence in humans is limited. Mosaic loss of the Y chromosome (mLOY) is a marker of genotoxicity and genomic instability that has been associated with certain cancers and may reflect intermediate effects of pesticide exposure.

Deciphering lung adenocarcinoma evolution and the role of LINE-1 retrotransposition.

Understanding lung cancer evolution can identify tools for intercepting its growth. In a landscape analysis of 1024 lung adenocarcinomas (LUAD) with deep whole-genome sequencing integrated with multiomic data, we identified 542 LUAD that displayed diverse clonal architecture. In this group, we observed an interplay between mobile elements, endogenous and exogenous mutational processes, distinct driver genes, and epidemiological features.

Benzene exposure and risk of colorectal cancer by anatomical subsite in the Norwegian offshore petroleum workers cohort.

Objective: To investigate the association between low levels of benzene exposure (≤0.879 parts per million [ppm]-years) and risk of colorectal cancer (CRC) including its anatomical subsites.

Methods: Among 25,347 male workers in the Norwegian Offshore Petroleum Workers (NOPW) cohort with offshore work history (1965-1998), 455 CRC cases were diagnosed 1999-2021.

Occupational exposures and kidney cancer among 25 000 male offshore petroleum industry workers: relative risks and healthy worker survivor bias.

Kidney cancer has been a suspected occupational disease in petroleum workers. Health conditions that are linked to kidney cancer may prompt termination or change of work, and thereby restrict occupational exposures in high-risk individuals, creating a healthy worker survivor bias (HWSB). We examined associations between occupational exposures and kidney cancer among males in the Norwegian Offshore Petroleum Workers (NOPW) cohort using a case-cohort design, with 169 incident cancers identified by linkage to national registry data (1999-2021) and a subcohort of 2090 non-cases, all employed 1965-1998.

Solvent Exposure, Genetic Susceptibility, and Risk of Bladder Cancer.

The New England Bladder Cancer Study has recently reported an increased bladder cancer risk with occupational exposure to mononuclear aromatic organic solvents, including exposure to benzene, toluene, and xylene and their combination BTX. However, the mechanisms by which BTX influence bladder cancer are unclear. In this study, we evaluated the interaction between BTX and genetic markers in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of these solvents.

Time-dependent relationship between urinary biomarkers of nucleic acid oxidation and colorectal cancer risk.

Purpose: Randomized controlled trials have failed to validate that neutralizing oxidative stress (OxS) through antioxidant supplementation reduces cancer risk. This study aims to prospectively investigate whether the relationship between systemic OxS and colorectal cancer (CRC) risk changes over the course of cancer development.

Methods: This study utilized a nested case-control design in two Shanghai cohorts for primary analysis and one US cohort for replication analysis.

Sex differences in anti-EBV antibody responses.

We investigated anti-EBV IgA and IgG responses by sex among 387 cancer-free individuals in Asia. Antibody responses were measured using an EBV proteome array to assess age-adjusted sex-specific associations with 404 EBV-antigens in 86 protein sequences via meta-analysis and pathway analysis by EBV stage. Males were more likely to have elevated IgA responses (P=0.

IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards.

Background: The 10 key characteristics (KCs) of carcinogens form the basis of a framework to identify, organize, and evaluate mechanistic evidence relevant to carcinogenic hazard identification. The 10 KCs are related to mechanisms by which carcinogens cause cancer. The () programme has successfully applied the KCs framework for the mechanistic evaluation of different types of exposures, including chemicals, metals, and complex exposures, such as environmental, occupational, or dietary exposures.

Overview of historical occupational exposure to trichloroethylene in China.

Objectives: Trichloroethylene (TCE) is a carcinogen that has been causally linked to kidney cancer and possibly other cancer sites including the liver and lymphatic system. Its use in China has increased since the early 1990s due to the growing metal and electronic industries. We aimed to summarize the major sources of occupational exposure to TCE over time in China.

Reproductive and Hormonal Factors and Thyroid Cancer Risk: Pooled Analysis of Prospective Cohort Studies in the Asia Cohort Consortium.

Given the female predominance of thyroid cancer, particularly in the reproductive age range, female sex hormones have been proposed as an etiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from nine prospective cohorts in the Asia Cohort Consortium to explore the association between 10 female reproductive and hormonal factors and thyroid cancer risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HR) and 95% confidence intervals (CI) were estimated and then pooled using a random-effects model.

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.

Reproductive factors and risk of epithelial ovarian cancer: results from the Asia Cohort Consortium.

Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women.

Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium.

The need for a cancer exposome atlas: a scoping review.

Background: Despite advances in understanding genetic susceptibility to cancer, much of cancer heritability remains unidentified. At the same time, the makeup of industrial chemicals in our environment only grows more complex. This gap in knowledge on cancer risk has prompted calls to expand cancer research to the comprehensive, discovery-based study of nongenetic environmental influences, conceptualized as the "exposome.