Environmental and Genetic Risk Factors for Epidemiologic Study on Nasopharyngeal Carcinoma in Taiwan: Epstein-Barr Virus, Cigarette Smoking, Familial Tendency, and Genetic Polymorphism
Date Issued
2009
Date
2009
Author(s)
Hsu, Wan-Lun
Abstract
Three studies were conducted to investigate the associations of Epstein-Barr virus (EBV), cigarette smoking, family history of nasopharyngeal carcinoma (NPC), and polymorphisms of DNA repair and cell cycle control/apoptosis genes with the risk of developing NPC. tudy 1. Epstein-Barr Virus and Cigarette Smoking on Nasopharyngeal Carcinoma: A Follow-up Studyhis study aimed to assess independent effects of Epstein-Barr virus (EBV) and cigarette smoking on nasopharyngeal carcinoma (NPC), which have never been assessed in long-term follow-up studies. A cohort of 9,622 men was enrolled from 1984 to 1986. Cox’s proportional hazard regression analysis was used to estimate multivariate-adjusted hazard ratio (HRadj) with its 95% confidence interval (CI). Increasing serum levels of anti-EBV VCA IgA and DNase were significantly associated with NPC risk in a dose-response relationship. The HRadj of developing NPC for low and high antibody levels compared with seronegatives was 9.5 and 21.4, respectively, for anti-EBV VCA IgA; and 1.6 and 16.0, respectively, for anti-EBV DNase. The HRadj was 3.0 for ≥30 pack-years of cumulative cigarette smoking compared with <30 pack-years as the referent. tudy 2. Associations of Family History and Epstein-Barr Virus Infection Seromarkers with Risk of Nasopharyngeal Carcinomahis study examined the impact of family history (defined as 2+ NPC cases in a family) on NPC risk after adjustment for anti-EBV seromarkers. We evaluated the longitudinal risk of NPC among males from NPC multiplex families against that observed among a second group of males from a community-based cohort study in Taiwan. Cox’s proportional hazard regression analysis was used to estimate multivariate-adjusted hazard ratio (HRadj) with 95% confidence interval (CI). In total, 1,019 males from the NPC multiplex family cohort and 9,622 males from the community cohort were in the analyses. Compared with participants in the community cohort, the HRadj of developing NPC was 13.9 for participants in the multiplex family cohort. The increased NPC risk for members of NPC multiplex families remained significantly elevated after adjustment for anti-EBV seromarkers and cigarette smoking habit (HRadj: 8.3). The HRadj (95% CI) was 37.0 for participants who were anti-EBV-seropositive and reported a family history of NPC compared with EBV-seronegatives individuals without such a history.tudy 3. Associations of Polymorphisms of DNA Repair Genes and Cell Cycle Control/Apoptosis Genes with Nasopharyngeal Carcinoma Riske conducted a community-based case-control study to investigate the genotypes of 334 NPC cases and 283 healthy community controls matched by sex, age, and residence. This study focused on effects of 31 genetic polymorphisms of 17 DNA repair and cell cycle control/apoptosis genes on the development of nasopharyngeal carcinoma (NPC). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of single nucleotide polymorphism (SNPs) and haplotype with NPC. Moreover, gene-environment interaction and gene dosage effect were also evaluated. The results showed a highly significant increased risk for NPC was associated with the BRCA2 N372H (OR = 1.4) and BRCA2 IVS24+5557 A>C (OR = 1.5). The EXO1 T439M, hMLH1 -93A>C, and CASP9 F136F had a 0.5-fold, 0.6-fold, and 0.5-fold reduced risk for NPC, respectively. In cumulative genetic risk analyses, individuals with four risk genotype (OR = 1.3), five (OR = 2.2), six (OR = 2.3) exhibited increased risks of NPC compared the number less than 3 risk genotypes as the reference, with a significant gene dosage effect. No significant interaction between gene and environment was found.
Subjects
nasopharyngeal carcinoma
epidemiology
risk factor
Epstein-Barr virus
cigarette smoking
familial tendemcy
genetic polymorphism
DNA repair gene
cell cycle control gene
apoptosis gene
Type
thesis
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