Neoplasms

All Conditions

Infections

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Epstein-Barr Virus Infections

Virus Diseases

Nasopharyngeal Carcinoma

Communicable Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

EBV-DNA next generation sequencing

Yaqian Han

The investigators aim to explore a new EBV DNA surveillance method with both high sensitivity and specificity in nasopharyngeal carcinoma (NPC) patients. the investigators aim to conduct plasma EBV DNA counting by next generation sequencing (NGS) in non-metastatic NPC patients on their diagnose, after two cycles of induction chemotherapy (IC), and 4-8 weeks after definitive radiotherapy. The investigators aim to explore whether sequencing-based counting is better than PCR analysis in plasma EBV-DNA surveillance, so as to monitoring tumor responses to treatment and for guiding individualized treatment adaptation in the future.

Sequencing-based Counting of Plasma Epstein-Barr Virus DNA in Non-metastatic Nasopharyngeal Carcinoma

Plasma EBV DNA analysis by NGS on enrollment, after 2 cycles of induction chemotherapy, and 4-8 weeks after definitive radiotherapy.

Measured from the day of enrollment until death due to any cause, or the last follow-upmeasured from the day of enrollment until death due to any cause, or the last follow-up visit.

Measured from the day of enrollment until death until distant metastasis , or the last follow-up visit.

Measured from the day of enrollment until death until local and/or regional recurrence, or the last follow-up visit.

Measured from the day of enrollment until treatment failure, death from any cause, or the last follow-up visit, whichever occurred first.

Patient reported quality of life would be evaluated using the Quality of Life Questionnaire-Core 30 module (QLQ-C30).

Exploratory biomarker analysis that would be able to predict patient treatment benefits, for example PD-L1 expression, antigen (other than EBV, eg. human cytomegalovirus(human cytomegalovirus \[HCMV\], TTV) DNA counting.

Hunan Cancer Hospital

Professor

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Malaria

Burkitt Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Protozoan Infections

Parasitic Diseases

Mosquito-Borne Diseases

Vector Borne Diseases

Lymphoma, B-Cell

Lymphosarcoma

B-cell Lymphoma

Children from East Africa diagnosed with BL

Matched controls from the local health clinics

Matched controls from the geographic region

Sam M Mbulaiteye, M.D.

Burkitt lymphoma (BL) is an aggressive monoclonal B-cell malignancy that is rare (sporadic) worldwide, but is 100-fold more common (endemic) in equatorial Africa, particularly among children. Epstein-Barr virus (EBV) and malaria are epidemiologically linked to endemic BL in epidemiologic studies, but questions remain about role of EBV variants and the evidence for association with malaria is weak. EBV is ubiquitous, yet only few children develop BL, possibly because only a few EBV variants are pathogenically relevant. The association of BL with malaria is based on ecologic and non-comparative clinical studies. Two case-control studies have reported significant association of high anti-malarial antibodies with BL (OR=5_ among children in Uganda and in Malawi, but selection bias (cases and controls came from dissimilar geographical areas) and reverse causality bias were limitations. Three studies were conducted in the 1960s and 70s to test association of carriage of malaria-resistance gene with BL, two of which reported a significant or marginal inverse association. These pioneering studies were small (240 cases all together) and looked at one polymorphism in one gene (sickle cell gene). Improvements in technologies to characterize genetic variation allow the EBV and malaria hypotheses to be examined with greater power by looking at genetic variation across multiple genes.

Epidemiology of Burkitt lymphoma in East African children and minors (EMBLEM) is a case-control study of 1500 BL cases and 3000 age-, sex- and residence-frequency matched controls we are proposing to conduct in East Africa. The study will enroll cases at four hospitals in four regions in East Africa, where malaria transmission is holoendemic and year round. The controls will be enrolled from general population attendees at Health Center II (HC-II) units where the cases originated. The primary study objectives are: 1) to test the hypothesis that genetic resistance to malaria is associated with a lower risk of BL, and 2) to use genome-wide association methods to discover genetic variation that may be associated with decreased or increased risk of BL. Because genetic variation conveys no information on actual exposure to malaria or EBV, in secondary analyses, we will use empiric epidemiological questionnaire and laboratory methods: a) to measure exposure to malaria and its association with BL, and b) to measure EBV variants and their association with BL. To examine issues related to bias and to obtain data to correct for deviations, we will also enroll 2250 population controls from 5% of the villages to obtain population distribution of key exposures variables. This data will be used to reweight the distribution in HC-II controls back to the general population.

...

Burkitt lymphoma (BL) is an aggressive monoclonal B-cell malignancy that is rare (sporadic) worldwide, but is 100-fold more common (endemic) in equatorial Africa, particularly among children. Epstein-Barr virus (EBV) and malaria are epidemiologically linked to endemic BL in epidemiologic studies, but questions remain about role of EBV variants and the evidence for association with malaria is weak. EBV is ubiquitous, yet only few children develop BL, possibly because only a few EBV variants are pathogenitically relevant. The association of BL with malaria is based on ecologic and non-comparative clinical studies. Two case-control studies have reported significant association of high anti-malarial antibodies with BL (OR=5_ among children in Uganda and in Malawi, but selection bias (cases and controls came from dissimilar geographical areas) and reverse causality bias were limitations. Three studies were conducted in the 1960s and 70s to test association of carriage of malaria-resistance gene with BL, two of which reported a significant or marginal inverse association. These pioneering studies were small (240 cases all together) and looked at one polymorphism in one gene (sickle cell gene). Improvements in technologies to characterize genetic variation allow the EBV and malaria hypotheses to be examined with greater power by looking at genetic variation across multiple genes.

The Epidemiology of Burkitt lymphoma in East African children and minors (EMBLEM) is a case-control study of 1500 BL cases and 3000 age-, sex- and residence-frequency matched controls we are proposing to conduct in East Africa. The study will enroll cases at four hospitals in four regions in East Africa, where malaria transmission is holoendemic and year round. The controls will be enrolled from general population attendees at Health Center II (HC-II) units where the cases originated. The primary study objectives are: 1) to test the hypothesis that genetic resistance to malaria is associated with a lower risk of BL, and 2) to use genome-wide association methods to discover genetic variation that may be associated with decreased or increased risk of BL. Because genetic variation conveys no information on actual exposure to malaria or EBV, in secondary analyses, we will use empiric epidemiological questionnaire and laboratory methods: a) to measure exposure to malaria and its association with BL, and b) to measure EBV variants and their association with BL. To examine issues related to bias and to obtain data to correct for deviations, we will also enroll 2250 population controls from 5% of the villages to obtain population distribution of key exposures variables. This data will be used to reweight the distribution in HC-II controls back to the general population.

Epidemiology of Burkitt Lymphoma in East Africa Children or Minors (EMBLEM)

Newly diagnosed case of BL confirmed by histology or cytology.

Positive diagnosis for parasitemia based on blood smear or antigenemia based on a rapid diagnostic test.

National Cancer Institute (NCI)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Acquired Immunodeficiency Syndrome

HIV Infections

Leukoplakia

Leukoplakia, Oral

Opportunistic Infections

AIDS-Related Opportunistic Infections

AIDS-Related Complex

Leukoplakia, Hairy

Precancerous Conditions

Pathological Conditions, Anatomical

Mouth Neoplasms

Mouth Diseases

Oral Cancer

Anti-Infective Agents

All Drugs and Chemicals

Acyclovir

Antiviral Agents

To evaluate the efficacy of oral acyclovir for the treatment and suppression of Epstein-Barr virus (EBV) related hairy leukoplakia (HL). To determine the long-term safety of acyclovir in the AIDS-related complex (ARC) patient with HL. To monitor the progression of HIV disease in the HL patient and compare to existing historical control data.

Treatment and Suppression of Hairy Leukoplakia in ARC Patients With Oral Acyclovir (ACV)

Glaxo Wellcome

Syndrome

Immunologic Deficiency Syndromes

Sarcoma

Sarcoma, Kaposi

Lymphoma, AIDS-Related

Neoplasms, Connective and Soft Tissue

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

RNA Virus Infections

Genital Diseases

Urogenital Diseases

Slow Virus Diseases

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Antibodies

Immunoglobulins

David A. Wohl

Ann C. Collier

William G. Powderly

Charles S. Rabkin

The purpose of this study is to find out why cancers develop in HIV-positive patients.

Cancer is a leading cause of death in AIDS patients. Common cancers in HIV-infected patients include Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), a cancer of the immune system. Risk factors include certain chemicals, viruses, and perhaps even anti-HIV drugs. Doctors would like to find out which risk factors are most important and how they relate to cancer in AIDS patients.

AIDS-associated malignancy represents a model system for investigations of carcinogenesis. There are few human conditions in which cancer rates are of the magnitude they are in HIV infection. While studies have investigated pre-cancer markers in HIV-infected patients, they have not correlated these markers with tumor samples. This study contributes to understanding oncogenesis of HIV-associated malignancies by establishing a collection of tumors linked with pre-cancer sera and lymphocyte specimens, as well as prospective questionnaire data.

At study entry, patients receive a comprehensive physical exam. Clinic staff interview the patient to collect data regarding medication history (particularly antiretroviral exposure), diet, occupational history, substance abuse, and sexual practices. This information is used to identify behavioral and environmental factors contributing to oncogenesis. In addition, baseline blood samples are analyzed for HHV-8 and EBV levels, anti-EBV and anti-HHV-8 antibodies, CD23, Th2 cytokines, tumor growth factors, chromosomal translocations associated with NHL, and other potential predictors of malignancy. At Month 6 and annually thereafter, patient records are abstracted for data on vital status, AIDS-defining illnesses, medications, and most recent CD4+ T cell and HIV RNA levels. At Years 1, 2, and 3, patients undergo physical exams and blood tests for malignancy surveillance. Any malignancies are biopsied and analyzed for oncogene identification and virology. The medical records of patients who die on study are reviewed to determine the cause of death and to rule out unreported cancer. No treatment is provided by this study.

A Study of Patients With AIDS Syndrome

Oncogenic Viral Pathogenesis and Cancer Risk Factors Among Patients With the Acquired Immunodeficiency Syndrome: A Prospective Cohort Study

National Institute of Allergy and Infectious Diseases (NIAID)

This is a high risk population of families for NPC

Allan Hildesheim, Ph.D.

Nasopharyngeal carcinoma is a rare tumor among Caucasians which occurs with high incidence among individuals of Chinese descent. The disease is believed to have a multifactorial etiology with genetic, viral, and other environmental factors being involved. Little is known, however, about the genetic component of this disease.

We have recently completed subject recruitment for a case-control study of NPC in Taiwan. Using information obtained from the NPC cases recruited into this NCI-sponsored case-control study as well as from a parallel cross-sectional study conducted by our Taiwanese collaborators, we have been able to identify 120-150 families with multiple family members affected with NPC.

The purpose of the study described herein is to determine the role of inherited genetic factors in the etiology of NPC and to examine the effect of these genetic susceptibility factors on risk associated with environmental exposures.

Families will initially be contacted via the proband who previously participated in our case-control and cross-sectional studies. Subsequently, informative family members will be asked to visit the study clinic to participate in the study. A family history questionnaire will be administered to the proband from each of the families selected for study. In addition, a risk factor questionnaire will be administered to all participating family members, and 30-40 ml of blood and an oral sample will be obtained from each study participant. Additional study components include medical record review to verify the diagnosis of NPC, retrieval of tumor tissue blocks as a source of DNA for study, and clinical exams on a sample of unaffected individuals to exclude the possibility of prevalent, undetected disease among family members.

Oral and laryngeal cancer families will also be recruited in a manner similar to that described for NPC families, in an attempt to elucidate genetic factors linked to the development of these two cancers....

Nasopharyngeal carcinoma is a rare tumor among Caucasians that occurs with high incidence among individuals of Chinese descent. The disease is believed to have a multifactorial etiology with genetic, viral, and other environmental factors being involved. Little is known, however, about the genetic component of this disease.

We previously completed a case-control study of NPC in Taiwan. Using information obtained from the NPC cases recruited into this NCI-sponsored case-control study and parallel sources, we have been able to identify 250 families with multiple family members affected with NPC.

The purpose of the study described herein is to determine the role of inherited genetic factors in the etiology of NPC and to examine the effect of these genetic susceptibility factors on risk associated with environmental exposures.

Families will initially be contacted via an affected proband. Subsequently, informative family members will be asked to visit the study clinic to participate in the study. A family history questionnaire will be administered to the proband and other affected family members from each of the families selected for study. In addition, a risk factor questionnaire will be administered to all participating family members, and 30-40 ml of blood and an oral sample will be obtained from each study participant. Additional study components include medical record review to verify the diagnosis of NPC, retrieval of tumor tissue blocks as a source of DNA for study, and clinical exams on a sample of unaffected individuals to exclude the possibility of prevalent, undetected disease among family members.

Oral and laryngeal cancer families will also be recruited in a manner similar to that described for NPC families, in an attempt to elucidate genetic factors linked to the development of these two cancers.

Family Study of Head and Neck Cancers in Taiwan

Background:

- Nasopharyngeal carcinoma (NPC) a common malignant tumor in southern China and Southeast Asia. Infection with Epstein-Barr virus is believed to be necessary for the development of NPC; non-viral environmental factors, such as dietary consumption of nitrosamines, cigarette smoking, betel nut chewing, wood dust exposure and possibly exposure to formaldehyde, have been implicated in the disease. Genetic susceptibility may also play an important role in the development of NPC. However, more information is needed on the connections between genetic and environmental factors in NPC, particularly in areas where the cancer risk appears to be greatest.

Objectives:

- To examine the main effects of genetic factors and environmental exposures (e.g., cigarette smoking, betel nut chewing, formaldehyde, wood dust) on nasopharyngeal carcinoma risk.

Eligibility:

* Cases: Individuals at least 21 years of age who have been diagnosed with NPC at one of the participating hospitals and have been residents of northern Taiwan for at least 6 months.
* Controls: Hospital patients with diseases other than NPC at least 21 years of age, matched to NPC patients based on hospital, age at diagnosis, gender, and ethnicity.

Design:

* This study involves a risk factor interview, medical record abstraction and biological sample collection.
* Participants will respond to interview questions about their lifestyle and risk factors thought to be involved in NPC development.
* All participants will provide blood and saliva samples for study. Participants who have been diagnosed with NPC will also provide consent to allow researchers to study tissue samples taken during tumor biopsies or surgeries.
* Treatment will not be provided as part of this protocol.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China and Southeast Asia. While infection with Epstein-Barr Virus (EBV) is believed to be necessary for the development of NPC, non-viral environmental factors have also been implicated in the carcinogenesis of NPC including consumption of salted fish and other nitrosamine containing preserved foods, formaldehyde and wood dust exposure, cigarette smoking, and betel nut chewing. In addition to environmental factors, it is widely accepted that genetic susceptibility plays an important role in the pathogenesis of NPC. Polymorphisms in genes involved in antigen presentation, nitrosamine metabolism and DNA repair have been suggested to be associated with NPC risk, and various chromosomal regions linked to NPC development have been reported. Two recently completed NPC GWAS have reported that the strongest evidence for disease association is observed for SNPs located on the 3.6 Mb Major Histocompatibility Complex (MHC) region on chromosome 6p21 where human leukocyte antigen (HLA) genes are located. These associations highlight the role of both environmental exposures and genomic variation in the etiology of NPC. However, the specific role of EBV on NPC pathogenesis is not completely understood and studies to date have had difficulty pinpointing the specific genetic factors involved in NPC pathogenesis due to the complexity of the MHC region and limited sample size of candidate gene studies.

DCEG investigators and their Taiwan colleagues have a longstanding history of studies to elucidate the role of environmental and genetic factors associated with NPC. A case-control study (375 cases; 327 controls) was conducted in the early 1990s and was followed by a large multiplex family study that was completed in 2006 (358 families; 3,216 individuals). Results from these studies have provided a substantial portion of the epidemiological evidence regarding factors linked to NPC development to date.

At this time, we propose a new case-control study in Taiwan designed to 1) comprehensively evaluate environmental risk factors for NPC; 2) systematically evaluate genetic risk factors for NPC for which previous GWAS and candidate-gene studies have suggested an association; and 3) explore gene-gene and gene-environment interactions for strong main effects identified in our study. In total, up to 2000 cases and 2000 controls are expected to be recruited from five participating hospitals in Northern Taiwan. Cases will consist of 550 incident cases ascertained retrospectively and 1350 incident cases ascertained prospectively. Controls will be hospital based; they will be frequency matched (1:1) to cases on age, gender and ethnicity, and will exclude individuals referred to the participating hospitals due to conditions associated with known NPC risk factors.

This project is a collaborative effort between investigators in Taiwan and at the NCI. Investigators in Taiwan will fund the field recruitment and data collection effort. Results from this study have the potential to further clarify currently controversial environmental risk factors as well as elucidate genetic factors of NPC.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sequencing-based Counting of Plasma Epstein-Barr Virus DNA in Non-metastatic Nasopharyngeal Carcinoma	NCT06321939	Nasopharyngeal ... Herpesvirus 4, ...	EBV-DNA next ge...	18 Years -	Hunan Cancer Hospital
Sequencing-based Counting of Plasma Epstein-Barr Virus DNA in Non-metastatic Nasopharyngeal Carcinoma	NCT06321939	Nasopharyngeal ... Herpesvirus 4, ...	EBV-DNA next ge...	18 Years -	Hunan Cancer Hospital
Epidemiology of Burkitt Lymphoma in East Africa Children or Minors (EMBLEM)	NCT01196520	Lymphoma, Non-H... Malaria Herpesvirus 4, ...		- 15 Years	National Institutes of Health Clinical Center (CC)
Treatment and Suppression of Hairy Leukoplakia in ARC Patients With Oral Acyclovir (ACV)	NCT00002026	Leukoplakia, Ha... HIV Infections	Acyclovir	18 Years -	NIH AIDS Clinical Trials Information Service
A Study of Patients With AIDS Syndrome	NCT00001120	Sarcoma, Kaposi Lymphoma, Non-H... HIV Infections Lymphoma, AIDS-...		18 Years -	National Institute of Allergy and Infectious Diseases (NIAID)
Sequencing-based Counting of Plasma Epstein-Barr Virus DNA in Non-metastatic Nasopharyngeal Carcinoma	NCT06321939	Nasopharyngeal ... Herpesvirus 4, ...	EBV-DNA next ge...	18 Years -	Hunan Cancer Hospital
Family Study of Head and Neck Cancers in Taiwan	NCT00342147	Nasopharyngeal ... Herpesvirus 4, ...		18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Environmental and Genetic Determinants of NPC	NCT01257100	Nasopharyngeal ... Herpesvirus 4, ...		21 Years - 100 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for herpesvirus 4, human