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Grant Details

Grant Number: 1R01CA115873-01A2 Interpret this number
Primary Investigator: Adami, Hans-Olov
Organization: Harvard School Of Public Health
Project Title: Gene-Environment EBV Interactions in the Etiology of Nasopharyngeal Carcinoma (Np
Fiscal Year: 2008


Abstract

DESCRIPTION: Gene-Environment EBV Interactions in the Etiology of NPC Summary/Abstract Our long-term objective is to provide a scientific basis for identifying individuals at high risk for undifferentiated nasopharyngeal carcinoma (NPC) and for instituting effective primary and secondary prevention measures. In China (where NPC is endemic in some areas) several smaller, often hospital- based studies have indicated that genetic susceptibility, Epstein-Barr virus (EBV) infection and other environmental factors are all important in the etiology of NPC. However, no previous study has allowed the simultaneous quantification of their roles, along with detailed analyses of the interplay among them. Therefore, our specific aims are 1) to identify the main effects of a) specific EBV strains, b) dietary factors, c) smoking and d) variation in genes Involved in carcinogen metabolism, DNA repair, production and regulation of cellular receptors and cytokines as well as candidate genes on chromosome 4 and 5; and 2) to identify key gene-environment-EBV interactions. Building on the collective experience of the Harvard School of Public Health in Boston, two major cancer centers in China, Karolinska Institute in Stockholm, the Northern California Cancer Center in Fremont, and the Fred Hutchinson Cancer Center in Seattle, and on extensive planning and pilot studies, we propose a population-based case-control study in two provinces in southern China with the world's highest incidence of NPC. With a total of 2,000 incident cases with histopathologically confirmed NPC and an equal number of population controls, we will carry out face-to-face interviews, collect tumor tissue and blood, and perform genotyping and other laboratory analyses. With the proposed large size of the study, we will have sufficient statistical power to detect main effects of genetic and environmental exposures conferring a relative risk as low as 1.2, along with moderate-sized interactions. Importantly, we will also develop a biologic bank of tissue, serum and DNA, which will be made available for other investigators and for future genetic studies. We consider this study timely because the sophistication of the Chinese institutions only recently has increased to the point where large-scale population-based molecular epidemiologic studies in both urban and rural areas have become feasible. In addition, recent improvements in high-throughput technology now make it feasible to conduct a large-scale study examining gene-environment-virus interactions. NPC Narrative: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southeast Asia, yet little is known about its causes. This study will examine genetic, viral, and environmental risk factors for NPC in southern China, where NPC rates are among the highest in the world. Our goal is to identify new ways to prevent NPC, as well as to improve the identification of high-risk individuals for early detection and successful treatment of NPC.



Publications

Oral fungal profiling and risk of nasopharyngeal carcinoma: a population-based case-control study.
Authors: Chen Y. , Li W. , Chang E.T. , Debelius J.W. , Manoharan L. , Zheng Y. , Li Y. , Huang G. , Adami H.O. , Knight R. , et al. .
Source: Ebiomedicine, 2023 Oct; 96, p. 104813.
EPub date: 2023-09-28 00:00:00.0.
PMID: 37776725
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Body mass index and body shape before treatment and nasopharyngeal carcinoma prognosis: A population-based patient cohort study in southern China.
Authors: Du Y. , Feng R. , Chang E.T. , Yin L. , Huang T. , Li Y. , Zhou X. , Huang Y. , Zhou F. , Su C. , et al. .
Source: International Journal Of Cancer, 2023-03-25 00:00:00.0; , .
EPub date: 2023-03-25 00:00:00.0.
PMID: 36965052
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Environmental Factors for Epstein-Barr Virus Reactivation in a High-Risk Area of Nasopharyngeal Carcinoma: A Population-Based Study.
Authors: Chen Y. , Chang E.T. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , Jia W.H. , et al. .
Source: Open Forum Infectious Diseases, 2022 May; 9(5), p. ofac128.
EPub date: 2022-03-15 00:00:00.0.
PMID: 35450082
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A comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma.
Authors: Zhou X. , Cao S.M. , Cai Y.L. , Zhang X. , Zhang S. , Feng G.F. , Chen Y. , Feng Q.S. , Chen Y. , Chang E.T. , et al. .
Source: Nature Communications, 2021-08-31 00:00:00.0; 12(1), p. 5189.
EPub date: 2021-08-31 00:00:00.0.
PMID: 34465768
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Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China.
Authors: Huang T. , Ploner A. , Chang E.T. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q. , Xie S. , Cao S. , et al. .
Source: The American Journal Of Clinical Nutrition, 2021-08-02 00:00:00.0; 114(2), p. 462-471.
PMID: 33963745
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Residence characteristics and risk of nasopharyngeal carcinoma in southern China: A population-based case-control study.
Authors: Chen Y. , Chang E.T. , Liu Z. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , et al. .
Source: Environment International, 2021 06; 151, p. 106455.
EPub date: 2021-02-27 00:00:00.0.
PMID: 33652252
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Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study.
Authors: Chen Y. , Chang E.T. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , Jia W.H. , et al. .
Source: Cancer, 2021-04-06 00:00:00.0; , .
EPub date: 2021-04-06 00:00:00.0.
PMID: 33823062
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Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.
Authors: Feng R. , Chang E.T. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , Zhang Y. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2021 03; 30(3), p. 545-553.
EPub date: 2020-12-10 00:00:00.0.
PMID: 33303643
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Subspecies Niche Specialization in the Oral Microbiome Is Associated with Nasopharyngeal Carcinoma Risk.
Authors: Debelius J.W. , Huang T. , Cai Y. , Ploner A. , Barrett D. , Zhou X. , Xiao X. , Li Y. , Liao J. , Zheng Y. , et al. .
Source: Msystems, 2020-07-07 00:00:00.0; 5(4), .
EPub date: 2020-07-07 00:00:00.0.
PMID: 32636333
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Chinese nonmedicinal herbal diet and risk of nasopharyngeal carcinoma: A population-based case-control study.
Authors: Lin C. , Cao S.M. , Chang E.T. , Liu Z. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Zhang Y. , et al. .
Source: Cancer, 2019-09-22 00:00:00.0; , .
EPub date: 2019-09-22 00:00:00.0.
PMID: 31544233
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Past and Recent Salted Fish and Preserved Food Intakes Are Weakly Associated with Nasopharyngeal Carcinoma Risk in Adults in Southern China.
Authors: Barrett D. , Ploner A. , Chang E.T. , Liu Z. , Zhang C.X. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , et al. .
Source: The Journal Of Nutrition, 2019-09-01 00:00:00.0; 149(9), p. 1596-1605.
PMID: 31127847
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Genome sequencing analysis identifies Epstein-Barr virus subtypes associated with high risk of nasopharyngeal carcinoma.
Authors: Xu M. , Yao Y. , Chen H. , Zhang S. , Cao S.M. , Zhang Z. , Luo B. , Liu Z. , Li Z. , Xiang T. , et al. .
Source: Nature Genetics, 2019-06-17 00:00:00.0; , .
EPub date: 2019-06-17 00:00:00.0.
PMID: 31209392
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Body mass index, body shape, and risk of nasopharyngeal carcinoma: A population-based case-control study in Southern China.
Authors: Feng R. , Chang E.T. , Liu Z. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , et al. .
Source: Cancer Medicine, 2019 Apr; 8(4), p. 1835-1844.
EPub date: 2019-02-21 00:00:00.0.
PMID: 30793524
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Reproductive history and risk of nasopharyngeal carcinoma: A population-based case-control study in southern China.
Authors: Feng R.M. , Chang E.T. , Liu Z. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , et al. .
Source: Oral Oncology, 2019 Jan; 88, p. 102-108.
EPub date: 2018-11-23 00:00:00.0.
PMID: 30616779
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Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma.
Authors: Xiao X. , Zhang Z. , Chang E.T. , Liu Z. , Liu Q. , Cai Y. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , et al. .
Source: American Journal Of Epidemiology, 2018-10-01 00:00:00.0; 187(10), p. 2117-2125.
PMID: 29701753
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FIVE AUTHORS REPLY.
Authors: Chang E.T. , Liu Z. , Hildesheim A. , Adami H.O. , Ye W. .
Source: American Journal Of Epidemiology, 2018-02-01 00:00:00.0; 187(2), p. 399.
PMID: 29126104
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Nasopharyngeal carcinoma risk prediction via salivary detection of host and Epstein-Barr virus genetic variants.
Authors: Cui Q. , Feng F.T. , Xu M. , Liu W.S. , Yao Y.Y. , Xie S.H. , Li X.Z. , Ye Z.L. , Feng Q.S. , Chen L.Z. , et al. .
Source: Oncotarget, 2017-11-10 00:00:00.0; 8(56), p. 95066-95074.
EPub date: 2016-08-09 00:00:00.0.
PMID: 29221111
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Development of a population-based cancer case-control study in southern china.
Authors: Ye W. , Chang E.T. , Liu Z. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , et al. .
Source: Oncotarget, 2017-10-20 00:00:00.0; 8(50), p. 87073-87085.
EPub date: 2017-07-29 00:00:00.0.
PMID: 29152064
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Active and Passive Smoking and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.
Authors: Chang E.T. , Liu Z. , Hildesheim A. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Xie S.H. , Cao S.M. , Shao J.Y. , et al. .
Source: American Journal Of Epidemiology, 2017-06-15 00:00:00.0; 185(12), p. 1272-1280.
PMID: 28459936
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Quantification Of Familial Risk Of Nasopharyngeal Carcinoma In A High-incidence Area
Authors: Liu Z. , Chang E.T. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Huang Q.H. , Xie S.H. , Cao S.M. , Shao J.Y. , et al. .
Source: Cancer, 2017-02-27 00:00:00.0; , .
PMID: 28241094
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Oral Hygiene and Risk of Nasopharyngeal Carcinoma-A Population-Based Case-Control Study in China.
Authors: Liu Z. , Chang E.T. , Liu Q. , Cai Y. , Zhang Z. , Chen G. , Xie S.H. , Cao S.M. , Shao J.Y. , Jia W.H. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2016 Aug; 25(8), p. 1201-7.
PMID: 27197279
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