In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the International Lung Cancer Consortium

10.1289/ehp.1002217Environmental Health Perspectives118121743-174

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers

The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers

Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4 - the AdAPT Method

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config)

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 x 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 x 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 x 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

RationaleBenzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer.ObjectivesWe aimed to examine the relationship between occupational benzene exposure and lung cancer.MethodsSubjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes.Measurements and main resultsAnalyses included 28048 subjects (12329 cases, 15719 controls). Lung cancer odds ratios ranged from 1.12 (95% CI: 1.03-1.22) to 1.32 (95% CI: 1.18-1.48) (Ptrend=0.002) for groups with the lowest and highest cumulative occupational exposure, respectively, compared to unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (PtrendPtrend=0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies.ConclusionWe found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including non-smokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene

Mercury content in hairs of mother-child pairs in Slovakia as a biomarker of environmental exposure

Abstract: The mercury content in hairs was determined in the framework of the European funded projects COPHES and DEMOCOPHES to test the feasibility of an EU-HBM (Human Biomonitoring) approach generating comparable data. The aim of the Slovak participation in DEMOCOPHES was to obtain and contribute the Slovak data to the harmonization of Human Biomonitoring. Pre-analytical and analytical phase for mercury in hair measurements and activities developed for the harmonization analysis within COPHES/ DEMOCOPHES projects were conducted under a strict quality assurance program (QA/QC). Total mercury in hair was determined by thermal decomposition-gold amalgamation atomic absorption spectroscopy (AMA-254 Advanced Mercury Analyzer.) Two interlaboratory comparison investigations (ICIs) and two external quality assessment schemes (EQUAS) were conducted before the beginning of the COPHES/DEMOCOPHES projects. The laboratory successfully completed both ICIs and EQUAS schemes and was allowed to analyze all DEMOCOPHES samples of the Slovak Republic. In summary, 129 mother-child pairs were recruited to pilot study of DEMOCOPHES in Slovakia from two different locations representing urban and rural environment. The analyzed data from Slovakia showed relationship between frequency of fi sh meals consumption (especially sea fi sh and sea food products) and mercury concentrations in hair of mothers and children. The exposure levels for a sampled population in Slovakia (children 0.092 (0.080-0.106) [µg.

Occupational exposure and laryngeal and hypopharyngeal cancer risk in central and eastern Europe.

A multicenter case-control study was conducted during 1999-2002 in four European countries (Poland, Romania, Russia, and Slovakia) to evaluate the role of occupational exposures in risk of laryngeal/hypopharyngeal cancer. Male cancer cases (34 hypopharyngeal, 316 laryngeal) with full data on occupational history and nonoccupational factors were compared with 728 hospital controls for occupational exposure to 73 suspected carcinogens. Occupational history was evaluated by industrial hygienists blinded to case/control status. Elevated risks for ever exposure to coal dust were found for both hypopharyngeal (odds ratio (OR) = 4.19, 95% confidence interval (CI): 1.18, 14.89) and laryngeal (OR = 1.81, 95% CI: 0.94, 3.47) cancer, with clear dose-response patterns. Inclusion of a 20-year lag in the analysis strengthened these associations. Hypopharyngeal cancer risk was also significantly associated with exposure to mild steel dust (OR = 3.04, 95% CI: 1.39, 6.64) and iron compounds and fumes (OR = 2.74, 95% CI: 1.29, 5.84), without clear dose-response relations. Laryngeal cancer was significantly associated with exposure to hard-alloys dust (OR = 2.23, 95% CI: 1.08, 4.57) and chlorinated solvents (OR = 2.18, 95% CI: 1.03, 4.61), without dose-response relations. A possible link between high formaldehyde exposure and laryngeal cancer was suggested. No association was found for exposure to asbestos or inorganic acid mists. These data indicate that occupational exposure to coal dust may play a role in laryngeal and hypopharyngeal cancer. Other possible relations need further evaluation