Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Genetic Predisposition to Disease

Disease Susceptibility

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Qing Lan, M.D.

Background:

* Women in Xuan Wei County, China, are almost all non-smokers, yet they have the highest lung cancer rate in that country.
* Non-smoking women in Xuan Wei who use smoky coal for cooking and heating homes can inhale 10 times higher levels of polycyclic aromatic hydrocarbons (PAH, compounds formed in many burning organic substances, including smoky coal) than someone who smokes 20 cigarettes a day.

Objectives:

* Determine the health effects of smoky coal in Xuan Wei and Fu Yuan counties in China's Yun Nan Province
* Determine how different levels of exposure to smoky coal and other types of fuel affect the amount of smoky coal emissions that are absorbed into the body
* Determine genetic risk factors for lung cancer in the study population and determine how they interact with smoky coal and PAH exposure.

Eligibility:

* Women from Xuan Wei and Fu Yuan counties between 18 and 79 years of age who have lung cancer and do or do not use smoky coal
* Women from Xuan Wei and Fu Yuan counties between 18 and 79 years of age who do not have lung cancer and do or do not use smoky coal

Design:

-Exposure assessment study for users of smoky coal - 150 households

Use of air badges, monitors, and dermal badges to determine subjects' exposure to smoky coal

Collection of blood, urine, cheek cell and sputum samples to measure the amount of smoky coal emissions absorbed into the body and evaluate the types of biologic changes they cause

Interview subjects about their health and family history, occupational exposures, lifestyle factors (e.g., tobacco smoking and diet), and inherited differences in genes

-Case-control study - 1,000 women

Collection of blood, urine, cheek cell and sputum samples to measure how amount of smoky coal emissions absorbed into the body and evaluate types of biologic changes they cause

Interview subjects about their health and family history, occupational exposures, lifestyle factors (e.g., tobacco smoking and diet), and inherited differences in genes

Gene analysis to determine if a genetic variation is associated with an increased or decreased risk of health effects from smoky coal exposure

Females in Xuan Wei County are almost all non-smokers, yet they have the highest lung cancer rate in China. Non-smoking women in Xuan Wei who use smoky coal in their home can inhale ten times higher levels of PAHs than a 20 cigarette per day active smoker, and air concentrations approach levels experienced by workers on the top-side of coke ovens. Several lines of research have provided strong support that the excess lung cancer in this region is caused primarily by PAHs derived from smoky coal exposure. As such, this region of China provides one of the best opportunities in the world to carry out a model study of gene-environment interactions in lung cancer. We have designed a hospital-based case-control study of 500 lung cancer cases and 500 controls among non-smoking women, with controls to be selected through a randomized recruitment design to achieve balance for the main effects of smoky coal exposure and ultimately greater power to detect interactions. The study will be carried out over a three-year period in Xuan Wei and Fu Yuan Counties in Yun Nan Province, China. In addition, we will be carrying out an exposure assessment study (n=150 households) to evaluate air and dermal exposure to PAHs from smoky coal use in order to model PAH exposure experienced by subjects in the case-control study. We will collect buccal cell, sputum, blood, and urine samples from all subjects. The primary goal of the study is to characterize genetic risk factors at the DNA level for lung cancer in this population and determine how they interact with smoky coal and PAH exposure. In addition, the hospital-based design will enable us to collect venous blood samples and cryopreserve lymphocytes, which will allow us to carry out state-of-the-art functional susceptibility assays such as testing ability to repair PAH-damaged DNA and apoptotic capacity, and to measure integrative markers of genomic stability such as telomere length and oxidative damage in mitochondrial DNA. These types of assays have never been conducted in this population and hold great promise to provide insights into cancer risk that will compliment those obtained by genotyping. This study will provide an important complement to and contrast with both DCEG and extramural studies of tobacco smoking and lung cancer, where unraveling the genetic component is challenging in part because hundreds of tobacco carcinogens in various combinations likely contribute.

Smoky Coal Exposure, Genetic Susceptibility, and Lung Cancer in Non-Smoking Women in China

A Hospital-Based Case-Control Study of Non-Smoking Women in Xuan Wei and Fu Yua, China: PAH Exposure, Genetic Susceptibility, and Lung Cancer

Outcome from this study will include the observation of response-gradient for PAHs exposure due to indoor burning biomass and risk of lung cancer.

Outcome will involve discovering genes related to lung cancer risks among non-smoking Asian women.

Outcome will also involve the GXE analysis to explore the interaction between genetic factors and environmental exposure.

National Cancer Institute (NCI)

Skin and Connective Tissue Diseases

Digestive System Diseases

Blood and Lymph Conditions

Immune System Diseases

Nervous System Diseases

Rare Diseases

Breast Neoplasms

Stomach Neoplasms

Lymphoma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Lymphosarcoma

Healthy female urban residents in Shanghai between ages of 40-70.

A prospective cohort study is proposed to evaluate occupational and environmental risk factors for cancer among women in Shanghai, China. Approximately 75,000 women aged 40-69 who reside in eight geographically defined communities in two urban districts of Shanghai will be recruited via a community-based cancer education program. All eligible subjects will be invited by local health workers from the neighborhood health station to the clinic for an interview and selected anthropometric measurements. The interview will elicit information on demographic background, diet, lifestyle factors, medical history, lifetime occupational history and residential history for the past 20 years. In addition, the women will be asked for information on their husbands' current and usual occupations, and demographic and a few other exposure factors. A spot urine sample and 10 ml of blood will be collected from all cohort members and stored at -70 degrees C for future assays of urine metabolites and DNA and hemoglobin adducts of selected occupational and environmental carcinogens, and polymorphic genes encoding enzymes that are involved in metabolism of relevant carcinogens. Cohort members and their husbands will be followed for cancer outcomes through biennial recontact and linkage with files of the population-based Shanghai Cancer Registry, of the Shanghai Vital Statistics, and of the Shanghai Resident Registry. Medical records and pathology slides will be reviewed for all cancer cases to verify their diagnosis. Post-diagnostic blood samples will be obtained from all cohort members diagnosed with cancer during the follow-up period and stored for future methodologic and etiologic studies. The proposed initial study period is 5 years, with an average follow-up of about 3.5 years. We anticipate, however, that follow-up will continue for 10 years or more.

A prospective cohort study is proposed to evaluate occupational and environmental risk factors for cancer among women in Shanghai, China. Approximately 75,000 women aged 40-69 who reside in eight geographically defined communities in two urban districts of Shanghai will be recruited via a community-based cancer education program. All eligible subjects will be invited by local health workers from the neighborhood health station to the clinic for an interview and selected anthropometric measurements. The interview will elicit information on demographic background, diet, lifestyle factors, medical history, lifetime occupational history and residential history for the past 20 years. In addition, the women will be asked for information on their husbands' current and usual occupations, and demographic and a few other exposure factors. A spot urine sample and 10 ml of blood will be collected from all cohort members. Among participants who did not provide a blood sample, a buccal cell sample will be collected. All biological samples will be stored at -70 degrees C for future assays of genetic polymorphisms, urine metabolites and DNA and hemoglobin adducts of selected occupational and environmental carcinogenACs. Cohort members and their husbands will be followed for cancer outcomes through annual recontact and linkage with files of the population-based Shanghai Cancer Registry, of the Shanghai Vital Statistics, and of the Shanghai Resident Registry. Medical records and pathology slides will be reviewed for all cancer cases to verify their diagnosis. Post-diagnostic blood samples will be obtained from all cohort members diagnosed with cancer during the follow-up period and stored for future methodologic and etiologic studies. The proposed initial study period is 5 years, with an average follow-up of about 3.5 years. We anticipate, however, that follow-up will continue for 10 years or more.

A Prospective Cohort Study of Occupational Exposures and Cancer Risk Among Women

Any cancer incidence, selected chronic diseases and all causemortality

Chromosome Aberrations

Oculocerebral Syndrome With Hypopigmentation

Background:

* Trichloroethylene (TCE) is a solvent used in many medical and industrial processes.
* TCE is a carcinogen (causes cancer) in rats, but its carcinogenicity in humans is unclear. There is some evidence of increased liver and kidney cancers and of an association with non-Hodgkin lymphoma in studies of workers exposed to TCE.
* The carcinogenicity and regulation of TCE is a matter of continuing debate.

Objectives:

* To determine if TCE exposure is associated with higher levels of genetic aberrations in certain white blood cells called lymphocytes.
* To determine if TCE exposure affects lymphocyte subsets and levels of certain hormones called cytokines.

Eligibility: Workers exposed to two different levels of exposure to TCE and unexposed workers in Guangdong Province, China.

Design:

* 45 workers exposed to more than 25 parts per million (ppm) TCE, 30 workers exposed to from 10 to less than 25 ppm TCE and 45 unexposed workers will be enrolled.
* Subjects wear small instruments at work that measure chemicals in the air for 1 or 2 days during the 2-week study period. Exposed workers also wear several small skin patches on one of the two days.
* Subjects provide blood and urine samples.
* Subjects answer a questionnaire about work, smoking and drinking, use of medicines, medical history, general health, hobbies, and exposure to radiation and exposure to various substances at home.

Trichloroethylene (TCE) is an industrial solvent used in degreasing, dry cleaning, and numerous other medical and industrial processes. It is a ubiquitous environmental contaminant of drinking water and is present in many EPA Superfund sites. TCE is a rodent carcinogen but its carcinogenicity in humans is unclear. There is some evidence for an elevation in liver and kidney cancers and somewhat more convincing evidence of an association with non-Hodgkin lymphoma (NHL) in epidemiological studies of occupationally exposed cohorts. Overall, the carcinogenicity of TCE and its regulation is a matter of continuing debate despite an extensive database of in vitro and in vivo animal studies and several cohort and case-control studies. IARC categorizes TCE as a probable human carcinogen. In order to address questions about TCE's potential carcinogenicity and mechanism of action in humans, we propose to conduct a cross-sectional study of early biologic effect biomarkers of genotoxicity and immunotoxicity in 45 workers exposed to greater than 25 ppm TCE, 30 workers exposed to 10-25 ppm TCE, and 45 unexposed controls in Guangdong Province, China. We will assess TCE exposure level quantitatively, collect other exposure information through a questionnaire, collect biological samples, and assay a series of biomarkers of susceptibility, intermediate and early biologic effects. Our primary goal is to determine if TCE exposure increases chromosomal aberrations in peripheral lymphocytes, with a secondary goal of determining if TCE alters levels of key cytokines in plasma and changes lymphocyte subset ratios. In addition, our collaborators at UC Berkeley will apply a new generation of cytogenetic and molecular techniques to study TCE's ability to cause specific types of chromosomal aberrations that have been associated with NHL and related hematological malignancies as well as the impact of TCE on mRNA expression and the proteome. The work will compliment previous and ongoing OEEB studies of populations exposed to TCE and has the potential to make an important contribution to what little is known about the early biologic effects of TCE in humans.

Plasma, Red blood cells, whole blood, cryopreserved lymphocytes, cryopreserved granulocytes, FISH cells, FISH slides, RNAlater, supernatant, buccal pellets, buccal slides, serum, clot, LeukLock, buffy coat, urine.

Cancer Markers Associated With Occupational Exposure to Trichloroethylene

A Cross-Sectional Study of Occupational Exposure to Trichloroethylene, Chromosomal Aberrations, and Related Biomarkers in Guangdong, China

The primary goal of the study is to determine if TCE exposure is associated with higher levels of chromosomal aberrations in peripherallymphocytes. The additional goals of the study, to be funded by extramural collaborators, are to evaluate TCE urinary metabolite patterns, alterations in specific types of chromosomal aberrations that have been detected in NHL and other hematopoietic malignancies, and alterations in mRNA expression and the proteome.

A secondary goal of the study is to determine if TCE exposure alters plasma cytokine levels and lymphocyte subsets.

Leukemia

Leukemia, Myeloid

Myeloid Leukemia

Anti-Infective Agents

All Drugs and Chemicals

Formaldehyde

Workers exposed to high levels of formaldehyde and unexposed workers in Guangdong Province, China.

Background:

* Research suggests that occupational exposure to formaldehyde is associated with increased risk for myeloid leukemia, but the significance of these findings is uncertain because of inconsistencies among studies and lack of knowledge of how formaldehyde can cause leukemia.
* Damage to the DNA of myeloid cells (type of white blood cell) or an environmental factor not affecting the cell genetic machinery may be involved.

Objective: To determine if formaldehyde exposure is associated with genetic or other changes in myeloid cells.

Eligibility: Workers exposed to high levels of formaldehyde and unexposed workers in Guangdong Province, China.

Design:

* 40 exposed workers and 40 unexposed workers will be enrolled.
* Subjects wear small instruments at work that measure chemicals in the air for 1 or 2 days.
* Subjects have a brief physical examination and provide blood, urine, and mouth rinse samples.
* Subjects answer a questionnaire about work, smoking and drinking, use of medicines, medical history, general health, exposure to radiation and exposure to various substances at home.

Research in industrial workers and professionals exposed to formaldehyde suggests that occupational exposure to this important chemical is associated with increased risk for myeloid leukemia. The significance, however, of these observations for occupational and environmental health is uncertain because of inconsistencies among epidemiologic studies and lack of a demonstrated mechanism through which formaldehyde can cause leukemia. Cytogenetic damage is one potential leukemogenic mechanism, but there are few studies of formaldehyde-exposed humans. Some experimental data suggest that epigenetic changes in myeloid cells could also be involved. We plan to study 40 workers exposed to high levels of formaldehyde and 40 unexposed controls to examine the hypothesis that formaldehyde is associated with these changes. To determine formaldehyde exposure, we will incorporate a number of methods, including questionnaires to determine potential past exposure and on-site monitoring to determine current average and peak intensities of exposure. We will then examine differences in aneuploidy and structural abnormalities in myeloid progenitor cells cultured from peripheral blood. We will specifically look for differences in genes associated with myeloid leukemia such as monosomy 7 and trisomy 8 using interphase and Octochrome FISH. We will also determine whether aberrant methylation in progenitor cells, specifically hypermethylation of genes associated with myeloid leukemia, is higher in those exposed to formaldehyde. This study will substantially contribute to our understanding of the leukemogenic potential of formaldehyde, which has important public health and regulatory implications.

Association of Formaldehyde Exposure to Myeloid Leukemia in Workers in Guangdong, China

Studies of Myeloid Progenitor Cells in Workers Exposed to Formaldehyde, a Putative Leukemogen

This study will determine if formaldehyde is associated with epigenetic changes in myeloid progenitor cells, including global methylation and hypermethylation in genes that have been linked to myeloid leukemia (ML) such as p15, HIC1, ER, CDH1 and ABL.

This study will determine if formaldehyde exposure is associated with aneuploidy in myeloid progenitor cells using interphase-FISH, with a particular focus on monosomy of chromosome 7 and aneuploidy of other relevant chromosomes, such as trisomy 8; and if formaldehyde exposure is associated with increased levels of structural aberrations relevant for myeloid leukemogenesis \[e.g., 5q-\] in myeloid progenitor cells using OctoChrome FISH, which will evaluate aberrations in all 24chromosomes.

Lymphoma, Non-Hodgkin

Lymphoma, Follicular

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Follicular Lymphoma

Hodgkin Lymphoma

Asian cases with lymphoid or myeloid neoplasma

Controls with selected non-cancer diagnosis who were hospitalized in Hong Kong, Chengdu and Tianjin of Mainland China, and Taiwan

Background:

- Lymphoma rates in Asia have been lower than in the West, but rates have been rising in recent years. Most studies of lymphoma patients have been conducted in the West. Less information is available about the factors that might contribute to the rise of lymphoma in Asia. Researchers want to collect medical and personal histories and samples from people who have recently been diagnosed with lymphoma. This information will help them study possible reasons for this increase.

Objectives:

- To collect samples and histories as part of an introductory study of lymphoma in Asia.

Eligibility:

* People between 18 and 79 years of age who have entered study hospitals in Hong Kong, Taiwan, and mainland China for treatment for any type of lymphoma.
* Healthy volunteers between 18 and 79 who have never had lymphoma.

Design:

* Participants will be screened with a physical exam and medical history.
* They will provide blood samples and cheek cell samples for testing.
* Participants will complete a questionnaire about their personal health history. They will answer questions about exposures to chemicals like pesticides. They will also be asked about family medical history and work and residential history. Finally they will answer questions about lifestyle factors like diet and exercise.
* They will give permission for the researchers to see their medical records. Researchers will also have access to any tumor samples collected as part of treatment.

The contribution of environmental, occupational and genetic factors to lymphoma has generated a series of novel findings in studies of Caucasians. However, none of the chemical associations have been conclusively established and the identification of the key, functional alleles in gene regions associated with risk of NHL requires further elucidation. Further, the ability to follow-up, confirm, and extend these observations is limited by the low prevalence and limited range of several important chemical exposures and the high to complete linkage disequilibrium among key candidate genetic loci in Western populations. To optimize the ability to build on and clarify these findings, it is necessary to investigate populations that differ from Caucasians in both exposure patterns and underlying genetic structure. A multidisciplinary case-control study of lymphoma in Asia provides an opportunity to replicate and extend recent and novel observations made in studies among Caucasians in a population that is distinctly different with regard to patterns of key risk factors, including range of exposures, prevalence of exposures, correlations between exposures, and variation in gene regions of particular interest. Thus, a hospital-based case-control study of lymphoma in Eastern Asia (i.e., AsiaLymph) of 4,200 cases and 4,200 controls to be enrolled over a three-year period will be conducted. In addition, 2,000 cases of myeloid leukemias and an additional 2,400 cases with less common lymphoma subtypes will be enrolled as well. The major postulated risk factors for evaluation in this study are chemical exposures (i.e., organochlorines, trichloroethylene, and benzene) and genetic susceptibility. Other factors potentially related to NHL, such as viral infections, UV exposure, medical conditions, and other lifestyle factors will also be explored. A particularly noteworthy aspect of AsiaLymph is central pathology review with immunophenotyping by two of the world s leading lymphoma pathologists, which will enable accurate analysis of findings by molecular and histologic subtypes. AsiaLymph represents the optimal next step in the DCEG lymphoma portfolio. AsiaLymph should confirm and extend previous findings, and yield novel insights into the causes of lymphoma and leukemia in both Asia and the West.

Study of Lymphoma in Asia

A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in Asia (AsiaLymph)

A large-scale evaluation of genes associated with lymphoma in Asian populations that parallels efforts being conducted in Caucasian populations (e.g., currently a genome-wide association study (GWAS)) would be particularly informative because of Asian population genetic differences in patterns of LD and local haplotype structure.

Other factors potentially related to NHL, such as viral infections, UV exposure, medical conditions, and other lifestyle factors will also beexplored.

Syndrome

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Patients with a confirmed diagnosis of AML or MDS (cases).

Patients treated for a primary malignancy (controls).

Interview

Jian Gu, PhD

The goal of this research study is to identify biologic and lifestyle factors that may increase a person's risk of developing acute myeloid leukemia or myelodysplastic syndrome after treatment for a previous cancer (treatment-related AML/MDS).

For this study, you will be asked to take part in a personal or mail interview. During the interview, you will be asked questions about your demographics (age, sex, etc.), any chemicals you may have been exposed to, your medical history, family history of cancer, your diet, and your smoking and alcohol use histories. It should take around 50 minutes to complete the interview. Treatment information from your medical records at M. D. Anderson will also be collected.

You will be asked to provide a saliva sample or have around 1 tablespoon of blood drawn for special tests. These tests will look for biologic factors associated with treatment-related AML/MDS.

Your participation in this study will be over once the interview has been completed and blood or saliva have been collected.

This is an investigational study. Up to 600 participants will take part in this study. All will be enrolled at M. D. Anderson.

Saliva or blood sample collected for special tests that will look for biologic factors associated with treatment-related AML/MDS.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Smoky Coal Exposure, Genetic Susceptibility, and Lung Cancer in Non-Smoking Women in China	NCT00482118	Lung Neoplasms		18 Years - 79 Years	National Institutes of Health Clinical Center (CC)
A Prospective Cohort Study of Occupational Exposures and Cancer Risk Among Women	NCT00342004	Lung Cancer Non-Hodgkin Lym... Breast Cancer Stomach Cancer Brain Cancer		40 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Cancer Markers Associated With Occupational Exposure to Trichloroethylene	NCT00481611	Industrial Hygi... Epidemiology Neoplasms		18 Years - 50 Years	National Institutes of Health Clinical Center (CC)
Association of Formaldehyde Exposure to Myeloid Leukemia in Workers in Guangdong, China	NCT01338285	Epidemiology Industrial Hygi... Neoplasms		18 Years - 50 Years	National Institutes of Health Clinical Center (CC)
A Prospective Cohort Study of Occupational Exposures and Cancer Risk Among Women	NCT00342004	Lung Cancer Non-Hodgkin Lym... Breast Cancer Stomach Cancer Brain Cancer		40 Years - 70 Years	National Institutes of Health Clinical Center (CC)
A Prospective Cohort Study of Occupational Exposures and Cancer Risk Among Women	NCT00342004	Lung Cancer Non-Hodgkin Lym... Breast Cancer Stomach Cancer Brain Cancer		40 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Study of Lymphoma in Asia	NCT01584141	Lymphoma, Folli... Lymphoma, Non-H... Multiple Myleom... Lympocytic, Fol... Leukemia Hodgkin Lymphom...		18 Years - 79 Years	National Institutes of Health Clinical Center (CC)
Molecular Epidemiology of Therapy-related Acute Myeloid Leukemia/Myelodysplastic Syndrome (AML/MDS)	NCT00525746	Leukemia Myelodysplastic...	Interview	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for molecular epidemiology