N02CP71011-26__Draft_Addendum_to_SOW.pdf

Studies Supported under Current Contract Addendum to SOW N02CP71011-26 Page 1 of 7

STUDIES SUPPORTED UNDER CURRENT CONTRACT

Under OEEB oversight, the contract will provide a wide range of support activities to Branch investigators, including meeting coordination, forms development, interviewer and abstractor training, subject selection, field supervision, development of computer-assisted personal interviewing instruments, interviewing (in person, telephone, mail) and abstracting, data coding, biologic specimen collection and data processing and analysis, tracing and follow-up of study participants, quality control, expertise in industrial hygiene and geographic information systems (GIS), and subcontracting for special services. Supported under this contract, under OEEB oversight, are feasibility projects, pilot studies, methodologic research, specialized tasks in large-scale studies, and full support to large-scale cross-sectional, case-control and cohort investigations.

Thirty studies received support under the current contract. Table 1 lists these studies and shows the specific tasks that were performed with contract support. Nineteen studies will continue to receive support under the new contract; these are noted with asterisks (**) on Table 1 and are summarized below. Some of these studies were largely supported by the contract and others received support only for specific tasks.

Agricultural Cohort Consortium (AGRICOH) OEEB investigators leading the AHS have established a consortium of agricultural cohorts, together with the International Agency for Research on Cancer (IARC). Several projects are underway, including a pooling project describing cancer incidence and mortality across nine AGRICOH cohorts, as well as pooling projects with the AHS and two other European cohorts focused on specific pesticides and lymphohematopoietic malignancies, breast cancer, and prostate cancer. The current contract has supported exposure assessment for specific pesticides in the Norwegian cohort for the prostate and breast cancer analyses. Future support will be needed for exposure assessment for additional pooling projects.

Agricultural Health Study (AHS) Since the mid-1990s, OEEB researchers have conducted a prospective cohort study of 57,310 licensed pesticide applicators and 32,346 of their spouses in Iowa and North Carolina to study the effects of pesticide and other agricultural exposures on numerous health outcomes. Although the AHS is supported primarily through its own research support contract, specific activities have been supported through the contract, such as GIS support and some exposure assessment. Future work will include GIS support for ongoing studies of drinking water contaminants, proximity to concentrated feeding operations and other airborne pollutants, occupational exposure assessment, and biologic specimen collection (tumor tissue).

Ambient Ultrafine Particles and Cancer Risk Study and Ultrafines Traffic Study This study is evaluating the relationship between levels of ambient outdoor ultrafine particulate matter (diameter <100nm; UFP) and lung cancer risk among the NIH-AARP cohort participants in Southern California. A retrospective exposure assessment is being developed from an ongoing mobile ambient pollution measurement campaign that aims to characterize the spatial distribution of outdoor UFP exposure within the study catchment area.

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Future support will be needed for secondary modeling and analytic components of the study, including additional health outcomes (e.g., all-cause and cause-specific mortality), exposure assessment replication efforts, and possible expansion to other AARP study states. GIS support will be needed to complete and extend work already in progress, to support model development, creation of GIS-based exposure metrics, linkage of metrics to cohort participants, spatial-descriptive analyses, and map generation.

Auto-Coding Free Text Job Titles This study was designed to develop an automated algorithm to code free-text job descriptions in epidemiologic studies to U.S. 2010 Standardized Occupational Classification (SOC) codes using natural language processing methods. This study has used occupational data from several OEEB studies to develop and validate the algorithm against expert-coded SOC codes. Expert coding has been supported by the current contract. The algorithm will be extended to other classification systems, such as the International Labor Organization’s ISCO. This study will continue to need support for activities related to expert coding of job descriptions to other classification system codes.

Biomarkers of Exposure and Effect in Agriculture (BEEA) Study OEEB investigators are conducting an ongoing field effort involving collection of biospecimens from at least 1,600 AHS farmers and 200 controls. Samples collected in this effort will be strategically used to investigate the biological mechanisms through which pesticides, endotoxin and other bioaerosols, and other agricultural exposures are associated with risk of various malignancies. The current contract has supported occupational exposure assessment and residential geocoding efforts within the BEEA study. Future work will involve ongoing occupational exposure assessment support, construction of GIS databases, data checking and quality control evaluation, and generating data files.

California Childhood Leukemia Study This study, designed to identify causes of childhood leukemia, is a collaborative effort with researchers at the University of California at Berkeley and the Cancer Prevention Institute of California. OEEB investigators are evaluating the risk of childhood leukemia in relation to exposure to pesticides and other chemicals. Support for the NCI portion of this study has been provided entirely under the current and past contract, and has included the collection of interview data and environmental samples; analyses of the dust samples for pesticides and other contaminants; and mapping of crops around homes. Future support will be needed to complete the construction of GIS databases on agricultural pesticide use in the area of subjects’ homes and to create other GIS-based environmental exposure metrics such as air pollution estimates.

Childhood Cancer and Parental Occupational Exposures in the International Childhood Cancer Cohort Consortium (I4C) The I4C is a consortium of prospective studies of parents and their children with information on parental occupational exposures during the pregnancy. Additionally, the Danish and Norwegian cohorts have geocoded residences during the pregnancy and at the child’s birth. OEEB required industrial hygiene support to harmonize the occupational coding of jobs for estimating occupational pesticide exposures via linkage to a job exposure matrix.

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Future support will be required to aid in the harmonization of job codes for the estimation of other occupational exposures such as solvents and dusts.

Chinese Benzene Cohort Study This comprehensive research effort on benzene includes a case-cohort study of leukemia, non- Hodgkin lymphoma (NHL), lung cancer, and benzene poisoning in a cohort of 75,000 benzene-exposed workers and 35,000 controls, and related cross-sectional molecular studies. A genome-wide association study (GWAS) of benzene hematotoxicity has been conducted using samples from these studies, which were almost entirely supported by the current contract. Future work will include data archiving, coordination of the replication phase of the benzene hematotoxicity GWAS, and scanning of additional samples at a laboratory in China from studies conducted by collaborators.

Decision Trees in Expert Exposure Assessment Study This study was designed to use classification tree (CT) models to extract agnostic patterns between occupational questionnaire responses and expert exposure estimates in OEEB case-control studies. The first use of this method was in the New England and Spanish Bladder Cancer Studies for exposure to diesel exhaust. The current contract provided support for activities related to extracting exposure variables from free-text job descriptions to use as model inputs and recoding variables from the job-specific modules. Future support will involve occupational exposure assessment and data programming.

Diesel Exhaust in Miners Study (DEMS) This collaborative study with NIOSH was designed to provide detailed information on the human cancer risks and to estimate the shape of the exposure-response curve for lung cancer.

This project consists of a cohort study, a nested case-control study of lung cancer, an exposure monitoring survey, and a retrospective exposure assessment component. The nested case-control study of lung cancer, was conducted with support under the previous contract. Both the case-control and cohort studies are completed. A follow up of the cohort is planned. Future support will involve conducting the National Death Index search and conducting telephone interviews with next of kin of newly identified cancer deaths and controls to obtain information on potential confounders.

Early Life Exposures in Agriculture OEEB investigators have launched a study of the offspring of the AHS cohort members. The AHS participants provided information about their children, and by constructing a cohort of these offspring, we will evaluate whether early exposures influence risk of many disease outcomes. Support will involve tracing and identification of these individuals using state and national cancer and mortality registries, design and administration of a questionnaire, collection of biological specimens, preparation of analytic files, quality control, and exposure assessment.

GWAS of Lung Cancer Among Non-smoking Asian Women OEEB investigators have conducted a GWAS of lung cancer among approximately 6,000 never-smoking cases and 6,000 never-smoking controls from 23 studies including those conducted in China, Hong Kong, Korea, Singapore, Taiwan, and Japan.

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The current contract provided support for an initial organizing meeting and critical help in coordinating the GWAS effort, including setting up subcontracts in China to coordinate and conduct scanning of several studies conducted there, coordinating shipments of DNA to genotyping labs, and collection and preparation of covariate and phenotype data files. Future support will involve coordinating receipt of samples and data for GWAS analysis of additional cases and controls from participating studies, coordination of replication efforts, and coordination of data collection and harmonization for subsequent gene-environment interaction and survival analyses. It will also support scanning of biological samples at a laboratory in China for samples collected by collaborators.

InterLymph Consortium Studies (NHL GWAS) OEEB investigators have conducted a large-scale GWAS of NHL among Caucasians within the InterLymph consortium and in collaboration with many members of the cohort consortium. The project includes a primary scan of 9,000 cases with one of the five most common subtypes, to which will be added genome-wide scan data from another 2,000 cases analyzed in previous studies. The current contract provided support for an initial organizing meeting and critical help in coordinating the effort, which involves more than two dozen studies. This has included collection and preparation of covariate and phenotype files from each study, harmonization of data across studies, and coordinating shipments of DNA to the CGR. Future support will involve coordinating receipt of samples and data for GWAS analysis of additional cases and controls from participating studies, coordination of replication efforts, and coordination of data collection and harmonization for subsequent gene-environment interaction and survival analyses.

Iowa Women’s Health Study This prospective study, initiated and funded by investigators at the University of Minnesota and University of Iowa, was designed to identify dietary and hormonal causes of cancer and other diseases among post-menopausal women in Iowa. It is one of the few large U.S. cohorts to collect information on drinking water source and duration, which allows for evaluation of risk of multiple cancer sites in relation to ingestion of nitrate and disinfection by-products. The current contract has supported geocoding of the enrollment and follow-up addresses and linkage of water source to databases with monitoring data for public water supplies. Using the geocoded address data, OEEB investigators also developed GIS-based land use metrics for assessing indirect exposure to agricultural pesticides. Future support will be needed to create other GIS-based environmental exposure metrics such as estimates of dioxin emissions near homes and air pollution estimates.

Multi-center Case-Control Study of Lymphoma in Asia (AsiaLymph) A multi-center, hospital-based case-control study of lymphoma and myeloid neoplasms in Eastern Asia has been conducted under the current contract. The major postulated risk factors for evaluation are chemical exposures and genetic susceptibility. Other factors potentially related to lymphoma in Asia, such as viral infections, UV exposure, medical conditions, and lifestyle factors will also be explored. Enrollment will be completed by the end of the current contract.

Future support will be needed for post-enrollment record collection and quality control reviews, central pathology review, data cleaning and editing, and shipment and analysis of biological samples.

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Shanghai Women’s Health Study This prospective, population-based cohort study of 74,942 women in Shanghai, China, is a collaborative project with Vanderbilt University and the Shanghai Cancer Institute. Most women in Shanghai work outside the home, often in industries with potential exposure to occupational carcinogens, providing a unique opportunity to study these exposures among women. The women have been actively followed up biennially for cancer incidence and changes in exposures since completion of the baseline recruitment in 2000. Many occupational, environmental, and molecular hypotheses are being evaluated in this cohort, as are interactions among exposures, lifestyle factors, and genetic risk factors. This study has received support from the current contract for occupational exposure assessment, and this will continue under the new contract. Selected laboratory assays for nested case-control studies will be supported as well.

Spanish Bladder Cancer Study and New England Bladder Cancer Study The Spanish Bladder Cancer Study was designed to identify new risk factors for bladder cancer and clarify known or suspected relationships in Spain, where exposures differ from those in the United States. This large, interdisciplinary case-control study has high-quality data on occupational and environmental exposures, lifestyle factors, and genetic susceptibility that may be related to exposures and disease. This study was entirely supported under the current and past contracts. Support included the collection of biologic specimens for biomarker and genetic studies and information for detailed assessment of occupational and environmental exposures.

Future support will involve detailed characterization of occupational exposures. In addition, both the Spanish Bladder Cancer Study and the New England Bladder Cancer Study (a population-based case-control study conducted in Maine, Vermont, and New Hampshire) have formed the core of the NCI bladder cancer GWAS over the last 5 years. Support will be needed to coordinate scanning and replication genotyping of samples from cases and controls from other collaborating studies that will be added to the GWAS data obtained from these two NCI studies to evaluate risk of bladder cancer overall and to study the relationship between exposures, genetic susceptibility, and molecularly defined subtypes of bladder cancer.

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Table 1. Studies Supported by Current Contract

SUPPORT ACTIVITIESa

STUDY

A

B

C

D

E

F

G

H

I

J

K

L

M

Acrylonitrile Cohort Study X X **Agricultural Cohort Consortium (AGRICOH) X

**Agricultural Health Study X X **Ambient Ultrafine Particles and Cancer Risk Study

X X X X

**Auto-Coding Free Text Job Titles X X

**Biomarkers of Exposure and Effect in Agriculture Study

X X

**California Childhood Leukemia Study X

Carbon Black Biomarker Study X X X X X X X X X X

**Childhood Cancer and Parental Occupational Exposures in the International Childhood Cancer Cohort Consortium

X

**Chinese Benzene Cohort Study X X X X X

**Decision Trees in Expert Exposure Assessment Study X X

Diesel Biomarker Study in China X X X X X X X X X X

**Diesel Exhaust in Miners Study X X X

**Early Life Exposures in Agriculture X X X X X X X X X X X X X

Esophageal Adenocarcinoma and

BEACON

X

**GWAS of Lung Cancer Among Non-smoking Asian Women

X X X X X X X

**InterLymph Consortium Studies X X X X X X

**Iowa Women’s Health Study X

Kidney Cancer GWAS X Missouri Dry Cleaners X

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SUPPORT ACTIVITIESa

STUDY

A

B

C

D

E

F

G

H

I

J

K

L

M

**Multi-center Case- Control Study of Lymphoma in Asia (AsiaLymph)

X X X X X X X X X X X

NCI-SEER NHL Study X X X **New England Bladder Cancer Study X X X X

NHL Washington County X NIH/AARP Diet and Health Study X

PLCO Bladder Renal

GWAS X

**Shanghai Women’s Health Study X X X

**Spanish Bladder Cancer Study X X

**Ultrafines Traffic Study X X X X U.S. Renal Cell Cancer Study X aSupport Activities:

A – Multi-center Coordination and Liaison B – Forms Development C – Study Subject Selection D – Interviewer/Abstractor/Measurer Training E – Field Supervision and/or Management F – Interviewing G – Record Abstraction and Coding H – Biologic Specimen Collection and Processing I – Data Processing, Computerization, Access to Data J – Quality Control K – Tracing and Follow-up L – GIS Support M – Exposure Assessment Support

** Support is expected to continue under the new contract.