title: Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: study design, methods and feasibility.
abstract: Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p=0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrollment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC.
authors.affiliation: Laboratory of Genomic Diversity, SAIC Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
authors.forename: Xiu Chan
authors.initials: XC
authors.lastname: Guo
authors.forename: Kevin
authors.initials: K
authors.lastname: Scott
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Victor
authors.initials: V
authors.lastname: David
authors.forename: George W
authors.initials: GW
authors.lastname: Nelson
authors.forename: Randall C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Holli H
authors.initials: HH
authors.lastname: Dilks
authors.forename: James
authors.initials: J
authors.lastname: Lautenberger
authors.forename: Bailey
authors.initials: B
authors.lastname: Kessing
authors.forename: Janice
authors.initials: J
authors.lastname: Martenson
authors.forename: Li
authors.initials: L
authors.lastname: Guan
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zheng
authors.forename: Guy
authors.initials: G
authors.lastname: de The
authors.forename: Jian
authors.initials: J
authors.lastname: Liao
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D012107:Research Design
chemical_list: D005819:Genetic Markers; D007070:Immunoglobulin A