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.

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.

Urinary mutagenicity and bladder cancer risk in northern New England.

The etiology of bladder cancer among never smokers without occupational or environmental exposure to established urothelial carcinogens remains unclear. Urinary mutagenicity is an integrative measure that reflects recent exposure to genotoxic agents. Here, we investigated its potential association with bladder cancer in rural northern New England.

Occupational exposure to organic solvents and risk of bladder cancer.

Background: Bladder cancer has been linked to several occupations that involve the use of solvents, including those used in the dry-cleaning industry.

Objectives: We evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study.

Methods: Exposure to solvents was quantitatively assessed using a job-exposure matrix (CANJEM).

Analysis of Several Common APOBEC-type Mutations in Bladder Tumors Suggests Links to Viral Infection.

Unlabelled: FGFR3 and PIK3CA are among the most frequently mutated genes in bladder tumors. We hypothesized that recurrent mutations in these genes might be caused by common carcinogenic exposures such as smoking and other factors. We analyzed 2,816 bladder tumors with available data on FGFR3 and/or PIK3CA mutations, focusing on the most recurrent mutations detected in ≥10% of tumors.

Urine pH and Risk of Bladder Cancer in Northern New England.

Background: Acidic urine pH is associated with rapid hydrolysis of N-glucuronide conjugates of aromatic amines into metabolites that may undergo metabolism in the bladder lumen to form mutagenic DNA adducts. We previously reported that consistently acidic urine was associated with increased bladder cancer risk in a hospital-based case-control study in Spain. Here, we conducted a separate study in northern New England to replicate these findings.

Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors.

Background: Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors.

Methods: Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study.

A Retrospective Study of the Adjunctive Use of Gabapentin With Benzodiazepines for the Treatment of Benzodiazepine Withdrawal.

Benzodiazepine withdrawal is a widespread problem with potentially severe and deadly consequences. Currently, the only medications available for treating benzodiazepine withdrawal are short-acting and long-acting benzodiazepines. Identifying other drugs to help in treating benzodiazepine withdrawal is necessary.

Diet quality, common genetic polymorphisms, and bladder cancer risk in a New England population-based study.

Purpose: We examined the interaction between common genetic bladder cancer variants, diet quality, and bladder cancer risk in a population-based case-control study conducted in New England.

Methods: At the time of enrollment, 806 bladder cancer cases and 974 controls provided a DNA sample and completed a diet history questionnaire. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010) score.

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

Background: By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk.

Identification of Genetic Risk Factors for Familial Urinary Bladder Cancer: An Exome Sequencing Study.

Purpose: Previous studies have shown an approximately two-fold elevation in the relative risk of urinary bladder cancer (UBC) among people with a family history that could not be entirely explained by shared environmental exposures, thus suggesting a genetic component in its predisposition. Multiple genome-wide association studies and recent gene panel sequencing studies identified several genetic loci that are associated with UBC risk; however, the list of UBC-associated variants and genes is incomplete.

Materials And Methods: We exome sequenced eight patients from three multiplex UBC pedigrees and a group of 77 unrelated familial UBC cases matched to 241 cancer-free controls.

Targeted Deep Sequencing of Bladder Tumors Reveals Novel Associations between Cancer Gene Mutations and Mutational Signatures with Major Risk Factors.

Purpose: Exome- and whole-genome sequencing of muscle-invasive bladder cancer has revealed important insights into the molecular landscape; however, there are few studies of non-muscle-invasive bladder cancer with detailed risk factor information.

Experimental Design: We examined the relationship between smoking and other bladder cancer risk factors and somatic mutations and mutational signatures in bladder tumors. Targeted sequencing of frequently mutated genes in bladder cancer was conducted in 322 formalin-fixed paraffin-embedded bladder tumors from a population-based case-control study.

Bladder cancer risk associated with family history of cancer.

Twin studies suggest a familial aggregation of bladder cancer, but elements of this increased familial risk of bladder cancer are not well understood. To characterize familial risk of bladder cancer, we examined the relationship between family history of bladder and other types of cancer among first-degree relatives and risk of bladder cancer in 1193 bladder cancer cases and 1418 controls in a large population-based case-control study. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between family history of bladder cancer (defined as at least one first-degree family member with bladder cancer or a cancer of any other site).

Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes.

Background: The International Agency for Research on Cancer (IARC) classifies diesel engine exhaust as carcinogenic to humans based on sufficient evidence for lung cancer. IARC noted, however, an increased risk of bladder cancer (based on limited evidence).

Objective: To evaluate the association between quantitative, lifetime occupational diesel exhaust exposure and risk of urothelial cell carcinoma of the bladder (UBC) overall and according to pathological subtypes.

Ingested Nitrate and Nitrite and Bladder Cancer in Northern New England.

Background: N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study.

Methods: Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls).

Validity of retrospective occupational exposure estimates of lead and manganese in a case-control study.

Objectives: The validity of surrogate measures of retrospective occupational exposure in population-based epidemiological studies has rarely been evaluated. Using toenail samples as bioindicators of exposure, we assessed whether work tasks and expert assessments of occupational metal exposure obtained from personal interviews were associated with lead and manganese concentrations.

Methods: We selected 609 controls from a case-control study of bladder cancer in New England who had held a job for ≥1 year 8-24 months prior to toenail collection.

Pooled study of occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma.

Objectives: To investigate the association between occupational exposure to aromatic hydrocarbon solvents and risk of multiple myeloma (MM) in a large, consortium-based study.

Methods: We pooled data on 2854 cases and 10 743 controls from nine studies participating in the InterLymph consortium. Occupational exposures to benzene, toluene and xylene were assigned by a job-exposure matrix, coupled with 'correction' of exposure probability by self-reported or expert-assessed exposure from the individual studies.

Potential effect modifiers of the arsenic-bladder cancer risk relationship.

Populations exposed to arsenic in drinking water have an increased bladder cancer risk and evidence suggests that several factors may modify arsenic metabolism, influencing disease risk. We evaluated whether the association between cumulative lifetime arsenic exposure from drinking water and bladder cancer risk was modified by factors that may impact arsenic metabolism in a population-based case-control study of 1,213 cases and 1,418 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between cumulative arsenic intake and bladder cancer stratified by age, sex, smoking status, body mass index (BMI), alcohol consumption and folate intake.

Bladder Cancer and Water Disinfection By-product Exposures through Multiple Routes: A Population-Based Case-Control Study (New England, USA).

Background: Ingestion of disinfection byproducts has been associated with bladder cancer in multiple studies. Although associations with other routes of exposure have been suggested, epidemiologic evidence is limited.

Objectives: We evaluated the relationship between bladder cancer and total, chlorinated, and brominated trihalomethanes (THMs) through various exposure routes.

Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI.

Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic.

Background: Bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than the United States overall. We explored reasons for this excess, focusing on arsenic in drinking water from private wells, which are particularly prevalent in the region.

Computer-based coding of free-text job descriptions to efficiently identify occupations in epidemiological studies.

Background: Mapping job titles to standardised occupation classification (SOC) codes is an important step in identifying occupational risk factors in epidemiological studies. Because manual coding is time-consuming and has moderate reliability, we developed an algorithm called SOCcer (Standardized Occupation Coding for Computer-assisted Epidemiologic Research) to assign SOC-2010 codes based on free-text job description components.

Methods: Job title and task-based classifiers were developed by comparing job descriptions to multiple sources linking job and task descriptions to SOC codes.