NPC

Gene-environment-EBV interactions in the etiology of nasopharyngeal carcinoma (NPC)

We are conducting a large, population-based case-control study of 2,000 NPC cases and 2,000 controls from Guangdong Province and Guangxi Autonomous Region in southern China to investigate the main and interactive effects of environmental and behavioral factors, EBV genetic variation, and host genetic variation on NPC risk.

Project leaders

Professor emeritus

Hans-Olov Adami

Phone: +46-(0)8-524 861 80
E-mail: Hans-Olov.Adami@ki.se

Professor

Weimin Ye

Phone: +46-(0)8-524 861 84
Organizational unit: Department of Medical Epidemiology and Biostatistics (MEB), C8
E-mail: Weimin.Ye@ki.se

Project description

Nasopharyngeal carcinoma (NPC) is an endemic cancer in southern China, where early epidemiological studies have indicated that genetic susceptibility, Epstein-Barr virus (EBV) infection, and other environmental factors are all important in the development of NPC.  However, no previous study has allowed the simultaneous quantification of the etiologic roles of these factors, along with detailed analyses of the interplay among them.  Therefore, to investigate the main and interactive effects of environmental and behavioral factors, EBV genetic variation, and host genetic variation on NPC risk, we are conducting a large, population-based case-control study of 2,000 NPC cases and 2,000 controls from Guangdong Province and Guangxi Autonomous Region in southern China.

Incident NPC cases are identified through a rapid case ascertainment system involving a network of contact physicians at regional hospitals where NPC is diagnosed and treated.  Controls are randomly selected from local total population registers and are frequency matched to the expected number of cases by age and sex.  Cases and controls are interviewed in person using a structured, computerized questionnaire designed to obtain detailed information on potential risk factors for NPC such as diet, smoking, and personal and family medical history.  Blood, hair, nail, and saliva samples are also collected for EBV serology, host and virus genotyping, and biomarker analyses.

The study has its main financing from the National Cancer Institute, National Institutes of Health, USA  and is being conducted in partnership with scientists from China (Sun Yat-Sen University Cancer Center, China Center for Disease Control and Prevention, Peking Union Medical College, Guangxi Medical University, Sihui Cancer Institute, Wuzhou Red Cross Hospital, Cangwu Cancer Institute, and Zhaoqing First People’s Hospital), Sweden (Karolinska Institutet), and the United States (Harvard School of Public Health, Fred Hutchinson Cancer Research Center, and Exponent, Inc.).  At present, the study is in the final year of fieldwork, with laboratory and statistical analyses set to begin shortly.

The field work has now been successfully finished and we did indeed exceed the charged number by enrolling around 2,500 cases and a similar number of controls. Even more importantly, the participation rate among eligible individuals - both cases and controls - is approximately 83%. During 2015, the database became cleaned. Since then, we are working on the first set of manuscripts, one dealing with description of the study design (and what this can learn us about prerequisites and opportunities for high quality population-based research in China), one paper on oral health as a risk factor for NPC and others on cigarette smoking and the heritability of NPC. These papers will be submitted for publication in early 2016 and followed by second wave of analyses based on questionnaire data alone, particularly early life experiences and diet.

An all collaborator meeting is scheduled in April 2016. During that meeting one main goal is to outline use of the biobank for genetic studies, EBV analyses etc. and also discuss how we can allocate adequate resources to undertake this work.

Partners

Sweden  Hans-Olov Adami, Weimin Ye, Ingemar Ernberg and Zhiwei Liu
China Yonglin Cai, Sumei Cao, Guomin Chen, Guangwu Huang, Qihong Huang, Wenlin Huang, Weihua Jia, Jian Liao, Qing Liu, Haiqiang Mai, Jianyong Shao, Shanghang Xie, Miao Xu, Zhe   Zhang and Yuming Zheng
US Ellen Chang, Liming Liang and Thomas Vaughan

External Advisory Board

Curtis Harris, Allan Hildesheim, Marie-Claire King, Xihong Lin, Youlin Qiao, and Weicheng You

Publications

Eight-signature classifier for prediction of nasopharyngeal [corrected] carcinoma survival.
Wang H, Sun B, Zhu Z, Chang E, To K, Hwang J, et al
J. Clin. Oncol. 2011 Dec;29(34):4516-25