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)

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Chlorotrianisene

Ethiodized Oil

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

116 hepatocellular carcinoma patients underwent TACE

no optimal dosage of doxorubicin in TACE procedures (ranging from 30 to 75 mg/m2 up to a maximum of 150 mg/m2 ) according to tumor size

Lipiodol dose should be over 5 ml if tumor diameter is less than 5 cm, and the maximum dose will be 10 ml when the tumor develops to more than 5 cm in diameter.

Lipiodol

Rehab H Werida, Ass Prof.

evaluate the prognostic value of genetic polymorphisms in HCC Egyptian patients undergoing TACE using lipiodol and doxorubicin.

Research Objectives This study aims to determine the predictive effect of ANG-2 and IL28B genetic polymorphisms in safety and efficacy of doxorubicin and lipiodol used for the treatment of Egyptian HCC patients. Moreover, this study will determine the association between genetic polymorphisms of ANG-2 and IL28B with HCC severity.

Patients \& Methods Study design Our study is a prospective study for HCC patients undergoing TACE of doxorubicin and lipiodol.

Sample Size Based on previous published incidence of gene it will be at least 116 patients. Efficacy and Safety

1. Target lesions response will be measured according to modified Response Evaluation Criteria in Solid Tumors (RECIST) to (15):

   Complete response, Partial response, Progressive disease and Stable disease.
2. Repeated TACE sessions will be planned individually based on the tumor response to the treatment protocol.
3. Follow up will be performed for detection of tumor size using triphasic CT scan as a measure of efficacy. Moreover, all patients will be reevaluated for CBC, liver and kidney functions, in the follow up visit, to detect incidence of any adverse effects.
4. Patients will be asked for any side effects such as (myelosuppression, anorexia, nausea, vomiting, and/or alopecia).
5. Patients will be followed for progression-free survival after receiving TACE.

Method \& Proposal Steps

1. Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University.
2. Patients will be recruited from Ain Shams University hepatoma group, EL Demerdash Hospital, Cairo, Egypt.
3. At baseline and follow up visits after TACE, all patients will be assessed for complete blood count (CBC), kidney function, liver function, liver enzymes, alpha fetoprotein (AFP) and viral markers. Moreover, triphasic pelviabdominal CT will be performed before and after TACE.
4. Serum samples will be collected for ANG-2 and IL28B genotyping.
5. Genetic polymorphisms of ANG-2 and IL28B will be detected by real time polymerase chain reaction (RT-PCR).

   * Five mls of whole blood will be collected then separation of plasma will be performed.
   * Extraction of genomic DNA from blood samples by DNA extraction kit.
   * DNA qualification will be performed by Nano drop.
   * Genotyping will be done by allelic discrimination using Taqman assays specific for each polymorphism.
   * Assays will be done according to manufacturer protocol using real time PCR machine.
6. All patients will receive lipiodol and doxorubicin during TACE. Doxorubicin dose will differ among patients according to tumor size, patient condition, patient's laboratory data and presence of hepatic arteriovenous fistula.
7. Appropriate statistical tests will be conducted to evaluate the significance of the results.
8. Results, conclusion, discussion and recommendations will be given.

Pharmacogenetic Study in Hepatocellular Carcinoma Patients.

Pharmacogenetic Study in Hepatocellular Carcinoma Patients Underwent TACE

Rehab Werida

Principal Investigator

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Nervous System Diseases

Breast Neoplasms

Arthritis

Arthralgia

Joint Diseases

Breast Diseases

Skin Diseases

Pain

Neurologic Manifestations

Letrozole

Anastrozole

Aromatase Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Femara(Letrozole) 2.5mg 1tab qd, Arimidex(Anastrozole) 1mg 1tab qd

Aromatase Inhibitor(Femara or Arimidex)

Eun Sook Lee, MD, PhD

The purpose of this study is to investigate the relationship between the side effects(especially arthralgia and arthritis) which appear in the patients who are prescribed aromatase inhibitor(AI) and the CYP19 genetic polymorphisms.

CYP19 Genetic Polymorphism & Aromatase Inhibitor(AI)

Significance of CYP19 Genetic Polymorphism on Musculoskeletal Symptom & Complication of Aromatase Inhibitor(AI)

Korea University

Korea University Anam Hospital

Eun Sook, Lee

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Heart and Blood Diseases

Blood and Lymph Conditions

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Rare Diseases

Kidney Diseases

Hypertension

Hematologic Neoplasms

Disease Progression

Chronic Kidney Disease-Mineral and Bone Disorder

Renal Insufficiency, Chronic

Renal Insufficiency

Vascular Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Chronic Disease

Hematologic Diseases

Chronic Graft Versus Host Disease

1. Patients with chronic nephropathies
2. Patients with acute nephropathy
3. Patients with nephrectomy
4. Candidate Patients to major surgery
5. Patients with decompensated heart failure undergoing either medical or surgical therapy
6. Acute critically ill patients (e.g sepsis, post-operative)
7. Patients with hypertension
8. Patients with hematologic cancer exposed to chemotherapeutic agents or undergoing allogeneic bone marrow transplantation.
9. Long-term surviving patients who received bone marrow transplantation.

genetic polymorphisms

Chiara Livia Lanzani, prof

Laura Zagato, biologist

Chiara Lanzani, MD

This study evaluates the role of genetic in the development and progression of different nephropaties with particular attention to:

* AKI
* CKD
* Hypertension
* ADPKD
* CKD-MBD
* Patients with decompensated heart failure undergoing either medical or surgery therapy
* Patients with hematologic cancer exposed to chemotherapeutic agents or undergoing allogeneic bone marrow transplantation
* glomerular diseases

Background: In the past ten years there's been a progressive increase in the prevalence of CKD and consequently in the number of dialysed patients (\~4% per year) in Italy. This is probably due to the increasingly ageing population and incidence of CV disease (cf. Lombardy Register). To date, diabetes and CV disease are the most common cause of end-stage renal disease (ESRD) requiring RRT. Nonetheless, intrinsic renal diseases still remain an important cause of CKD. In the past few years, various environmental factors have been identified that affect the clinical progression of kidney disease: blood pressure control, lipid and glycemic profile (expecially in the setting of diabetic nephropaty), uric acid level and acid-base homeostasis. Recently, there have been found some genes responsible for monogenic hereditary diseases such as ADPKD (PKD1 e PKD2) and Alport syndrome (COL4A3/COL4A4/COL4A5). It is known that there's an important phenotypic heterogeneity among different patients with the same disease even in the same family because of incomplete penetrance \[5\]. Furthermore, it is well known that familiarity overbear all other risk factors in predicting the development of hypertension and its progression toward CKD. Many scientific findings show the link between some genetic polymorphisms (e.g ACE, adducin) and disease severity or development of various complications. There is now, increasingly scientific evidence that genetic palys an important role even in the development and progression of multifactorial renal disease with both protective or promoting possible pathways. Thus, It would seem that interactions between environmental and genetic factors are responsible for disease phenotypic heterogeneity and its progression.

Aim of the study:

* Extend the knowledge on genetic modifiers involved in disease progression to better classify patients in homogeneous groups based on aetiology and concomitant risk factors. According to the underlying pathology, patients will be assessed either alone or with their family to evaluate the phenotypic heterogeneity.
* Evaluate the role of drugs that targets genetic or environmental factors.
* Assess the role of gentic background in the development of CV complications in CKD patients undergoing dyalisis.
* Assess the role of immature progenitor cells in the progression of kidney disease.
* Evaluate the role of endogenous Ouabain to identify at increased risk for AKI: 1) Postoperative patients. 2) patients with decompensated heart failure undergoing surgery or PCI. 3) patients with severe hypovolemic shock due to either cardiologic causes (e.g AMI) or from other causes (e.g sepsis, hypertensive crisis) 4) patients with hematologic cancer exposed to chemotherapeutic agents or undergoing allogeneic bone marrow transplantation.
* Identify the presence of genetic modifiers influencing the development and progression of CKD.
* Evaluate the role of genetic polymorphism in the transition from hypertension to kidney disease.
* Assess the role of salt intake in BP control and CKD progression either alone or in the presence of genetic modifiers.
* Evaluate the role of protein intake restriction in CKD progression eitehr alone or in the presence of genetic modifiers.
* Identify cortical bone lesions in CKD
* Assess the role of genetic, nutritional and biochemical factors involved in the cortical bone development
* Evaluate the role of genetic in the development of hypertension in patients who received allogenic bone marrow transplantation.

The genetic polymorphisms that will be considered, based on current knowledge are:

* Alpha, beta, gamma Adducin (ADD1, ADD2, ADD3),
* Renin Angiotensin System (RAAS),
* Glomerular proteins: nephrine, podocin, cadherin.
* Renal tubular transport systems (Na-Cl cotransport, Na channel, lithium, Cl channel, K channel, Ca channel, Amino Acids, specialized tubular transporters ouabain, drugs, digoxin, aquaporins, ANP, BNP).
* Genes linked to the metabolism and function of endogenous ouabain (eg LSS) and Klotho (eg KL).
* Polycystin 1, polycystin 2 (PKD1 and PKD2), uromodulline, S. di Alport (COL4A3/COL4A4/COL4A5)

For the study of any further genetic polymorphisms, additional amendments to this research protocol will be formulated.

Genetics in the Progression of Nephropathies

The Genetic Contribution to Progression of Kidney Disease

Ospedale San Raffaele

Clinical Assistant

Immune System Diseases

Lymphoma

Leukemia

Lymphoma, Non-Hodgkin

Lymphoma, Follicular

Hodgkin Disease

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

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.

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)
Pharmacogenetic Study in Hepatocellular Carcinoma Patients.	NCT05291338	Hepatocellular ...	Doxorubicin Lipiodol	20 Years - 75 Years	Damanhour University
CYP19 Genetic Polymorphism & Aromatase Inhibitor(AI)	NCT00973505	Breast Neoplasm... Arthralgia Arthritis Genetic Polymor...	Aromatase Inhib...	18 Years - 80 Years	Korea University Anam Hospital
Genetics in the Progression of Nephropathies	NCT06416761	AKI CKD Ckd-Mbd CKD (Chronic Ki... ADPKD Hypertension Hematologic Mal... Bone Marrow Tra...	genetic polymor...	18 Years -	Ospedale San Raffaele
Pharmacogenetic Study in Hepatocellular Carcinoma Patients.	NCT05291338	Hepatocellular ...	Doxorubicin Lipiodol	20 Years - 75 Years	Damanhour University
Pharmacogenetic Study in Hepatocellular Carcinoma Patients.	NCT05291338	Hepatocellular ...	Doxorubicin Lipiodol	20 Years - 75 Years	Damanhour University
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)
Genetics in the Progression of Nephropathies	NCT06416761	AKI CKD Ckd-Mbd CKD (Chronic Ki... ADPKD Hypertension Hematologic Mal... Bone Marrow Tra...	genetic polymor...	18 Years -	Ospedale San Raffaele

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