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An epidemiological and molecular study of the relationship between smoking, risk of nasopharyngeal carcinoma, and Epstein-Barr virus activation.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 2012 Sep 19; Vol. 104 (18), pp. 1396-410. Date of Electronic Publication: 2012 Sep 12. - Publication Year :
- 2012
-
Abstract
- Background: Elevated levels of antibodies against antigens in the Epstein-Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence.<br />Methods: We conducted a case-control study using data from male case patients (n = 1316) and control subjects (n = 1571) living in Guangdong Province, an area in China at high risk for NPC, to study potential NPC risk factors and EBV inducers. Two independent healthy male populations from a second high-risk area (n = 1657) and a low-risk area (n = 1961) were also included in the analysis of potential EBV inducers using logistic regression models. In vitro assays were performed to investigate the effect of cigarette smoke extract on EBV activation in two EBV-positive cell lines. All statistical tests were two-sided.<br />Results: Smoking was associated with an increased risk of NPC among the Guangdong participants with 20-40 and 40 or more pack-years vs never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to 2.32, respectively; P (trend) < .001). Smoking was the only factor linked to EBV seropositivity among the expanded control group and the independent low-risk population. In vitro experiments showed that cigarette smoke extract promoted EBV replication, induced the expression of the immediate-early transcriptional activators Zta and Rta, and increased transcriptional expression levels of BFRF3 and gp350 in the lytic phase.<br />Conclusion: Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation.
- Subjects :
- Adult
Aged
Carcinoma
Case-Control Studies
Cell Line, Tumor
China epidemiology
Dose-Response Relationship, Drug
Epstein-Barr Virus Infections immunology
Feeding Behavior
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Regulation, Viral
Herpesvirus 4, Human drug effects
Herpesvirus 4, Human genetics
Herpesvirus 4, Human immunology
Herpesvirus 4, Human metabolism
Humans
Immediate-Early Proteins metabolism
Immunoglobulin A blood
Incidence
Logistic Models
Luciferases analysis
Male
Middle Aged
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms virology
Odds Ratio
Plasmids
Reverse Transcriptase Polymerase Chain Reaction
Risk Factors
Trans-Activators metabolism
Transfection
Antibodies, Viral blood
Asian People statistics & numerical data
Epstein-Barr Virus Infections complications
Herpesvirus 4, Human isolation & purification
Nasopharyngeal Neoplasms epidemiology
Nasopharyngeal Neoplasms etiology
Smoking adverse effects
Virus Activation
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2105
- Volume :
- 104
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 22972969
- Full Text :
- https://doi.org/10.1093/jnci/djs320