Nasopharyngeal cancer (NPC) has a very distinct geographic and ethnic distribution, occurring at high rates among ethnic Chinese from southeastern China and at much lower rates among Caucasian populations. While infection with the Epstein Barr virus (EBV) is believed to be necessary for development of the cancer, other factors, both genetic and exogenous, are also thought to be important. To investigate genetic, dietary, occupational, and behavioral factors related to the etiology of NPC, two studies were conducted in Taiwan - a case-control study of approximately 1,000 individuals and a multiplex family study of approximately 3,000 individuals (350 families). To date, our results suggest an association between risk and specific variants of the enzyme CYP2E1 and several DNA repair genes, specific patterns of HLA and KIR genes, and long-term cigarette smoking. High intakes of nitrosamines and nitrite during childhood and weaning also were associated with increased risks. Occupational exposures to wood dusts also appeared to affect risk;in contrast, formaldehyde exposure was not a significant risk factor. Exogenous risk factors identified within our family study were similar to those observed from our case-control study. Evaluation of gene expression profiles from nasopharynx tumor and normal cells suggest that genes involved in DNA repair and in the metabolism of nitrosamines are involved in NPC pathogenesis. Results from our tissue-based expression studies also suggest the possibility of loss-of-heterozygosity on the telomeric end of chromosome 14 in NPC, and that EBV gene expression within NPC tumor cells affect the expression of host genes involved in immune presentation. This suggests a possible mechanism by which EBV manages to evade immune surrveillance in NPC. Uaffected individuals from NPC multiplex families have been shown in our study to have elevated levels of antibodies against EBV compared to the general population. To follow-up on this finding, we have evaluated the value of EBV serology to predict subsequent NPC risk among unaffected individuals from NPC multiplex families. We observed that individual with elevated antibody levels against several EBV markers are at a 4 to 6-fold increased risk of developing NPC within 10 years, but the low specificity of the antibodies evaluated suggest that improvements are required before such serology-based tests can be used clinically.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010211-01
Application #
8157954
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2010
Total Cost
$157,994
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Liu, Zhiwei; Coghill, Anna E; Pfeiffer, Ruth M et al. (2018) Patterns of Interindividual Variability in the Antibody Repertoire Targeting Proteins Across the Epstein-Barr Virus Proteome. J Infect Dis 217:1923-1931
Correia, Samantha; Palser, Anne; Elgueta Karstegl, Claudio et al. (2017) Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA. J Virol 91:
Chang, Ellen T; Liu, Zhiwei; Hildesheim, Allan et al. (2017) Active and Passive Smoking and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China. Am J Epidemiol 185:1272-1280
Coghill, Anna E; Bu, Wei; Nguyen, Hanh et al. (2016) High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma. Clin Cancer Res 22:3451-7
Lo, Yen-Li; Pan, Wen-Harn; Hsu, Wan-Lun et al. (2016) Partial Least Square Discriminant Analysis Discovered a Dietary Pattern Inversely Associated with Nasopharyngeal Carcinoma Risk. PLoS One 11:e0155892
Bei, Jin-Xin; Su, Wen-Hui; Ng, Ching-Ching et al. (2016) A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry. Cancer Epidemiol Biomarkers Prev 25:188-192
Liu, Zhiwei; Coghill, Anna E; Pfeiffer, Ruth M et al. (2016) Birth order and risk of nasopharyngeal carcinoma in multiplex families from Taiwan. Int J Cancer 139:2467-73
Hildesheim, Allan (2013) Invited commentary: Epstein-Barr virus-based screening for the early detection of nasopharyngeal carcinoma: a new frontier. Am J Epidemiol 177:251-3
Hsu, Wan-Lun; Pan, Wen-Harn; Chien, Yin-Chu et al. (2012) Lowered risk of nasopharyngeal carcinoma and intake of plant vitamin, fresh fish, green tea and coffee: a case-control study in Taiwan. PLoS One 7:e41779
Yu, Kelly J; Gao, Xiaojiang; Chen, Chien-Jen et al. (2009) Association of human leukocyte antigens with nasopharyngeal carcinoma in high-risk multiplex families in Taiwan. Hum Immunol 70:910-4

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