Gene-environment-Epstein-Barr virus interactions in the etiology of nasopharyngeal carcinoma
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, the 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.
Principal Investigator: Hans-Olov Adami, M.D., Ph.D., Department of Epidemiology, Harvard School of Public Health
Co-Investigators: Ellen Chang, Sc.D., NCCC; Weimin Ye, M.D., M.Sc., Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; Zeng Yi-Xin, M.D., Ph.D., Sun Yat-Sen University Cancer Center; Zeng Yi, M.D., Ph.D., Chinese Center for Disease Control and Prevention; Thomas Vaughan, M.D., M.P.H., Program in Epidemiology, Fred Hutchinson Cancer Research Center; Walter Willett, M.D., and Peter Kraft, Ph.D., Department of Nutrition and Department of Epidemiology (respectively), Harvard School of Public Health.
Funding: National Cancer Institute |
