Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: study design, methods and feasibility.
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.
Guo
Xiu Chan
XC
Laboratory of Genomic Diversity, SAIC Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Scott
Kevin
K
Liu
Yan
Y
Dean
Michael
M
David
Victor
V
Nelson
George W
GW
Johnson
Randall C
RC
Dilks
Holli H
HH
Lautenberger
James
J
Kessing
Bailey
B
Martenson
Janice
J
Guan
Li
L
Sun
Shan
S
Deng
Hong
H
Zheng
Yuming
Y
de The
Guy
G
Liao
Jian
J
Zeng
Yi
Y
O'Brien
Stephen J
SJ
Winkler
Cheryl A
CA
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
D005819:Genetic Markers; D007070:Immunoglobulin A