Identifying environmental risk factors for inflammatory bowel diseases: a Mendelian randomization study

Several studies have examined environmental factors and inflammatory bowel diseases (IBD) using traditional approaches; however, provided results are still conflicting. Our aim was to determine whether lifestyle and nutrient exposures, related to IBD in observational meta-analyses, influence IBD risk using a Mendelian randomization (MR) approach. A two-sample MR approach was applied on summary-level genome-wide association results. Genetic variants strongly associated with measures of tobacco smoking, obesity and fat distribution, physical activity, and blood levels of vitamins and fatty acids were evaluated on genetic data from international IBD consortia including a total of 25,042 IBD cases (12,194 cases of Crohn's disease (CD) and 12,366 cases of ulcerative colitis (UC)) and 34,915 controls. Our results indicated that, among lifestyle exposures, being a smoker was positively associated with CD (OR 1.13, P=0.02), but it was not associated with UC risk (OR 0.99, P=0.88). Body-mass index (BMI) and body fat percentage were positively associated with CD (OR 1.11, P=0.02, per standard deviation (SD) of 4.6 kg/m(2); and OR 1.50, P=3x10(-10), per SD of 6.6%; respectively); while for UC, BMI was inversely associated (OR 0.85, P=5x10(-5); per SD) and body fat percentage showed a OR of 1.11 (P=0.11; per SD). Additionally, among nutrient exposures, omega-3 fatty acids levels were inversely associated with CD (OR 0.67, P=2x10(-6)). Our MR results did not support a protective effect for being a smoker on UC risk; however, they are compatible with a risk effect for higher body fat proportion and a protective role for higher levels of omega-3 fatty acids on CD etiology

Genetic Population Structure Analysis in New Hampshire Reveals Eastern European Ancestry

Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the population into six distinct genetic subgroups. We then correlated self-reported ancestry of the individuals with the Bayesian clustering results. Finnish and Russian/Polish/ Lithuanian ancestries were most notably found to be associated with genetic substructure. The ancestral results were further explained and substantiated using New Hampshire census data from 1870 to 1930 when the largest waves of European immigrants came to the area. We also discerned distinct patterns of linkage disequilibrium (LD) between the genetic groups in the growth hormone receptor gene (GHR). To our knowledge, this is the first time such an investigation has uncovered a strong link between genetic structure and ancestry in what would otherwise be considered a homogenous US population

Lung Cancer in a U.S. Population with Low to Moderate Arsenic Exposure

BackgroundLittle is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water.ObjectivesWe examined associations between arsenic and lung cancer.MethodsA population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level).ResultsArsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease.ConclusionAlthough this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies

Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article

Environmental And Occupational Exposures And Amyotrophic Lateral Sclerosis In New England

Background: Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS). Objective: To evaluate environmental and occupational exposures as risk factors for sporadic ALS. Methods: We performed a case control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness. Results: Self-reported job-or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% C11.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status. Conclusions: Our study contributes to a growing body of literature implicating occupational-and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors. (C) 2017 S. Karger AG, Base

Oklahoma's dirty dozen: Unwanted invasive plants

The Oklahoma Cooperative Extension Service periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

The Contribution of Benzene to Smoking-Induced Leukemia

Cigarette smoking is associated with an increased risk of leukemia; benzene, an established leukemogen, is present in cigarette smoke. By combining epidemiologic data on the health effects of smoking with risk assessment techniques for low-dose extrapolation, we assessed the proportion of smoking-induced total leukemia and acute myeloid leukemia (AML) attributable to the benzene in cigarette smoke. We fit both linear and quadratic models to data from two benzene-exposed occupational cohorts to estimate the leukemogenic potency of benzene. Using multiple-decrement life tables, we calculated lifetime risks of total leukemia and AML deaths for never, light, and heavy smokers. We repeated these calculations, removing the effect of benzene in cigarettes based on the estimated potencies. From these life tables we determined smoking-attributable risks and benzene-attributable risks. The ratio of the latter to the former constitutes the proportion of smoking-induced cases attributable to benzene. Based on linear potency models, the benzene in cigarette smoke contributed from 8 to 48% of smoking-induced total leukemia deaths [95% upper confidence limit (UCL), 20-66%], and from 12 to 58% of smoking-induced AML deaths (95% UCL, 19-121%). The inclusion of a quadratic term yielded results that were comparable; however, potency models with only quadratic terms resulted in much lower attributable fractions--all < 1%. Thus, benzene is estimated to be responsible for approximately one-tenth to one-half of smoking-induced total leukemia mortality and up to three-fifths of smoking-related AML mortality. In contrast to theoretical arguments that linear models substantially overestimate low-dose risk, linear extrapolations from empirical data over a dose range of 10- to 100-fold resulted in plausible predictions

Tumor-Associated Microbiome: Where Do We Stand?

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies

GCAT|Genomes for life: a prospective cohort study of the genomes of Catalonia

PURPOSE: The prevalence of chronic non-communicable diseases (NCDs) is increasing worldwide. NCDs are the leading cause of both morbidity and mortality, and it is estimated that by 2030, they will be responsible for 80% of deaths across the world. The Genomes for Life (GCAT) project is a long-term prospective cohort study that was designed to integrate and assess the role of epidemiological, genomic and epigenomic factors in the development of major chronic diseases in Catalonia, a north-east region of Spain. PARTICIPANTS: At the end of 2017, the GCAT Study will have recruited 20 000 participants aged 40-65 years. Participants who agreed to take part in the study completed a self-administered computer-driven questionnaire, and underwent blood pressure, cardiac frequency and anthropometry measurements. For each participant, blood plasma, blood serum and white blood cells are collected at baseline. The GCAT Study has access to the electronic health records of the Catalan Public Healthcare System. Participants will be followed biannually at least 20 years after recruitment. FINDINGS TO DATE: Among all GCAT participants, 59.2% are women and 83.3% of the cohort identified themselves as Caucasian/white. More than half of the participants have higher education levels, 72.2% are current workers and 42.1% are classified as overweight (body mass index ≥25 and <30 kg/m2). We have genotyped 5459 participants, of which 5000 have metabolome data. Further, the whole genome of 808 participants will be sequenced by the end of 2017. FUTURE PLANS: The first follow-up study started in December 2017 and will end by March 2018. Residences of all subjects will be geocoded during the following year. Several genomic analyses are ongoing, and metabolomic and genomic integrations will be performed to identify underlying genetic variants, as well as environmental factors that influence metabolites

Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO)

Purpose: To investigate the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) lower lung cancer risk. Methods: We analysed pooled individual-level data from seven case-control and one cohort study in the International Lung Cancer Consortium (ILCCO). Relative risks for lung cancer associated with self-reported history of aspirin and other NSAID use were estimated within individual studies using logistic regression or proportional hazards models, adjusted for packyears of smoking, age, calendar period, ethnicity and education and were combined using random effects meta-analysis. Results: A total of 4,309 lung cancer cases (mean age at diagnosis 65 years, 45% adenocarcinoma and 22% squamous-cell carcinoma) and 58,301 non-cases/controls were included. Amongst controls, 34% had used NSAIDs in the past (81% of them used aspirin). After adjustment for negative confounding by smoking, ever-NSAID use (affirmative answer to the study-specific question on NSAID use) was associated with a 26% reduction (95% confidence interval 8 to 41%) in lung cancer risk in men, but not in women (3% increase (-11% to 30%)). In men, the association was stronger in current and former smokers, and for squamous-cell carcinoma than for adenocarcinomas, but there was no trend with duration of use. No differences were found in the effects on lung cancer risk of aspirin and non-aspirin NSAIDs. Conclusions Evidence from ILCCO suggests that NSAID use in men confers a modest protection for lung cancer, especially amongst ever-smokers. Additional investigation is needed regarding the possible effects of age, duration, dose and type of NSAID and whether effect modification by smoking status or sex exists