RESUMO
The cancer of upper aerodigestive tract (UADT) is a common cancers in the world. However, its lifetime risk by consumption of alcohol, betel and cigarettes remain to be elucidated. This study aimed to estimate lifetime risk of distinct UADT cancers and assess their associations with alcohol, betel and cigarette consumption. Three cohorts of 25,611 men were enrolled in 1982-1992 in Taiwan. The history of alcohol, betel and cigarette consumption was enquired through questionnaire interview. Newly developed UADT cancers were ascertained through computerized linkage with national cancer registry profile. Lifetime (30-80 years old) risk and multivariate-adjusted hazard ratio (HRadj) of distinct UADT cancers by alcohol, betel and cigarette consumption were estimated. A total of 269 pathologically confirmed cases of UADT cancers were newly-diagnosed during 472,096 person-years of follow-up. The lifetime risk of UADT cancer was 9.42 and 1.65% for betel chewers and nonchewers, 3.22 and 1.21% for cigarette smokers and nonsmokers and 4.77 and 1.85% for alcohol drinkers and nondrinkers. The HRadj (95% confidence interval) of developing UADT cancer was 3.36 (2.51-4.49), 2.02 (1.43-2.84), 1.90 (1.46-2.49), respectively, for the consumption of betel, cigarette and alcohol. Alcohol, betel and cigarette had different effect on cancers at various anatomical sites of UADT. The cancer risk from the mouth, pharynx, esophagus to larynx increased for alcohol and cigarette consumption, but decreased for betel consumption. Alcohol, betel and cigarette consumption are independent risk predictors for distinct UADT cancers.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Areca , Neoplasias de Cabeça e Pescoço/epidemiologia , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologiaRESUMO
BACKGROUND: The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region. METHODS: To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3). FINDINGS: After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A). CONCLUSION: Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.
Assuntos
Cromossomos Humanos Par 6/genética , Predisposição Genética para Doença , Antígenos HLA-A/genética , Neoplasias Nasofaríngeas/genética , Alelos , Carcinoma , Intervalos de Confiança , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Haplótipos/genética , Humanos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Razão de Chances , Fatores de Risco , TaiwanRESUMO
BACKGROUND: A case-control study was conducted to evaluate the role of adult diet on nasopharyngeal carcinoma (NPC) in Taiwan. METHODS: A total of 375 incident NPC cases and 327 controls matched to the cases on sex, age, and residence were recruited between July 1991 and December 1994. A structured questionnaire inquiring complete dietary history, socio-demographic characteristics, and other potential confounding factors was used in the personal interview. Unconditional logistic regression analysis was used to estimate multivariate-adjusted odds ratio (OR(adj)) with 95% confidence interval (CI) after accounting for known risk factors. RESULTS: Fresh fish (OR(adj), 0.56; 95% CI, 0.38-0.83 for the highest vs. lowest tertile of intake), green tea (OR(adj), 0.61; 95% CI, 0.40-0.91 for drinking ≥1 times/week vs. never) and coffee (OR(adj), 0.56; 95% CI, 0.37-0.85 for drinking ≥0.5 times/week vs. never) were inversely associated with the NPC risk. No association with NPC risk was observed for the intake of meats, salted fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources was associated with a decreased NPC risk (OR(adj), 0.62; 95% CI, 0.41-0.94 for the highest vs. lowest tertile). CONCLUSION: The study findings suggest that certain adult dietary patterns might protect against the development of NPC.
Assuntos
Café , Ingestão de Líquidos , Peixes , Neoplasias Nasofaríngeas/epidemiologia , Plantas/química , Chá , Vitaminas , Adulto , Idoso , Animais , Carcinoma , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/prevenção & controle , Fatores de Risco , Taiwan/epidemiologiaRESUMO
In the present study, the authors compared the long-term risk of nasopharyngeal carcinoma (NPC) of male participants in an NPC multiplex family cohort with that of controls in a community cohort in Taiwan after adjustment for anti-Epstein-Barr virus (EBV) seromarkers and cigarette smoking. A total of 43 incident NPC cases were identified from the 1,019 males in the NPC multiplex family cohort and the 9,622 males in the community cohort, for a total of 8,061 person-years and 185,587 person-years, respectively. The adjusted hazard ratio was 6.8 (95% confidence interval (CI): 2.3, 20.1) for the multiplex family cohort compared with the community cohort. In the evaluation of anti-EBV viral capsid antigen immunoglobulin A and anti-EBV deoxyribonuclease, the adjusted hazard ratios were 2.8 (95% CI: 1.3, 6.0) and 15.1 (95% CI: 4.2, 54.1) for those positive for 1 EBV seromarker and positive for both seromarkers, respectively, compared with those negative for both EBV seromarkers. The adjusted hazard ratio was 31.0 (95% CI: 9.7, 98.7) for participants who reported a family history of NPC and who were anti-EBV-seropositive compared with individuals without such a history who were anti-EBV-seronegative. The findings suggest that both family history of NPC and anti-EBV seropositivity are important determinants of subsequent NPC risk and that the effect of family history on NPC risk cannot be fully explained by mediation through EBV serologic responses.
Assuntos
Predisposição Genética para Doença/epidemiologia , Herpesvirus Humano 4/imunologia , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/etiologia , Adulto , Antígenos Virais/sangue , Biomarcadores Tumorais/sangue , Estudos de Coortes , Desoxirribonucleases/sangue , Família , Feminino , Humanos , Imunoglobulina A/sangue , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/sangue , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Inquéritos e Questionários , Taiwan/epidemiologia , Proteínas Virais/sangueRESUMO
This study aimed to assess independent effects of EBV and cigarette smoking on nasopharyngeal carcinoma, which have never been assessed in long-term follow-up studies. A cohort of 9,622 men was enrolled from 1984 to 1986. Blood samples collected at study entry were tested for antibodies against EBV antigens (anti-EBV) viral capsid antigen immunoglobulin A and DNase. The cigarette smoking habit was inquired through questionnaire interview. Newly developed nasopharyngeal carcinoma cases were ascertained through computerized linkage with national cancer registry profile. Cox's proportional hazard regression analysis was used to estimate multivariate-adjusted hazard ratio with its 95% confidence interval (95% CI). During the follow-up of 173,706 person-years, 32 pathologically confirmed nasopharyngeal carcinoma cases were identified >1 year after recruitment. Increasing serum levels of anti-EBV viral capsid antigen immunoglobulin A and DNase were significantly associated with nasopharyngeal carcinoma risk in a dose-response relationship. The multivariate-adjusted hazard ratio (95% CI) of developing nasopharyngeal carcinoma for low and high antibody levels compared with seronegatives was 9.5 (2.2-40.1) and 21.4 (2.8-161.7), respectively, for anti-EBV viral capsid antigen immunoglobulin A (P < 0.001 for trend), and 1.6 (0.5-4.6) and 16.0 (5.4-47.1), respectively, for anti-EBV DNase (P < 0.001 for trend). The shorter the time interval between study entry and nasopharyngeal carcinoma diagnosis, the higher was the proportion of anti-EBV viral capsid antigen immunoglobulin A among nasopharyngeal carcinoma patients. The multivariate-adjusted hazard ratio (95% CI) was 3.0 (1.3-7.2) for > or =30 pack-years of cumulative cigarette smoking compared with <30 pack-years as the reference. The longer and heavier the cigarette smoking habit, the higher was the nasopharyngeal carcinoma risk. Anti-EBV viral capsid antigen immunoglobulin A, anti-EBV DNase, and long-term heavy cigarette smoking are independent nasopharyngeal carcinoma risk predictors.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Nasofaríngeas/etiologia , Fumar/efeitos adversos , Adulto , Anticorpos Antivirais/análise , Antígenos Virais/imunologia , Proteínas do Capsídeo/imunologia , Estudos de Coortes , Seguimentos , Herpesvirus Humano 4/imunologia , Humanos , Imunoglobulina A/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/imunologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Most adults have been infected with EBV. Many studies have indicated that antibodies against specific EBV antigens, particularly IgA antibodies, can be predictive or prognostic of EBV-associated malignancies, such as NPC. We hypothesized that healthy individuals from families with a history of multiple members affected with NPC (who therefore might be genetically susceptible to NPC themselves) might have an EBV antibody profile that is distinct from that seen in healthy individuals from the community at large. To explore this possibility and examine determinants of anti-EBV antibody levels in healthy, high-risk individuals, we evaluated data from 2 parallel studies of NPC in Taiwan, which included 1,229 healthy members of families in which 2 or more individuals were affected with NPC and 320 controls from the community at large. Blood collected from participants was tested for IgA antibodies against EBV VCA and EBNA-1 and for neutralizing antibodies against EBV DNase using standard assays. We observed evidence of familial aggregation of EBV seroreactivity among individuals from high-risk, multiplex NPC families. Anti-VCA IgA and anti-EBNA-1 IgA antibody seroprevalence in unaffected family members of NPC cases was 5-6 times higher than in members of the community (p < 0.01). This elevated seroprevalence among unaffected individuals from high-risk families was observed regardless of the relationship of the unaffected individual to the closest affected relative (siblings, parents, children or spouses). No sociodemographic or environmental factors examined were found to strongly and consistently correlate with elevated seroprevalence, but patterns emerged of increasing seroprevalence among older individuals and among females. Unaffected individuals from high-risk NPC families have elevated anti-EBV IgA antibody titers. The etiologic and clinical implications of this finding remain to be established.
Assuntos
Anticorpos Antivirais/análise , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/imunologia , Predisposição Genética para Doença , Imunoglobulina A/análise , Neoplasias Nasofaríngeas/virologia , Adolescente , Adulto , Idoso , Carcinoma/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Linhagem , Fatores de Risco , Estudos Soroepidemiológicos , TaiwanRESUMO
Nitrosamine consumption and polymorphisms in CYP2E1, the product of which is involved in the activation of nitrosamines into reactive intermediates, have been shown to be associated with nasopharyngeal carcinoma (NPC) risk. Given that reactive intermediates created during nitrosamine metabolism are capable of DNA damage, we further hypothesized that differences between individuals in their ability to repair DNA damage might be important in NPC pathogenesis. To evaluate this hypothesis, this study focused on effects of genetic polymorphisms of DNA repair genes hOGG1 and XRCC1 on the development of NPC. We conducted a case-control study to investigate the genotypes of 334 patients with NPC and 283 healthy community controls matched by sex, age, and residence. The PCR-based RFLP assay was used to identify genetic polymorphisms. After adjustment for sex, age, and ethnicity, the odds ratio (OR) of developing NPC for hOGG1 codon 326 genotypes of Ser/Cys and Cys/Cys compared with the Ser/Ser genotype was 1.6 (95% CI, 1.0-2.6). For XRCC1 codon 280 genotypes of Arg/His and His/His compared with the Arg/Arg genotype, the OR was 0.64 (95% CI, 0.43-0.96). Among subjects with putative high-risk genotypes for both hOGG1 and XRCC1, the OR was 3.0 (95% CI, 1.0-8.8). Furthermore, subjects with putative high-risk genotypes for hOGG1, XRCC1, and CYP2E1 had an OR of disease of 25 (95% CI, 3.5-177). Polymorphisms of the DNA repair genes hOGG1 (codon 326) and XRCC1 (codon 280) are associated with an altered risk of NPC. Carriers of multiple putative high-risk genotypes have the highest risk of developing NPC.
Assuntos
Carcinoma/genética , Dano ao DNA , DNA Glicosilases/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético , Adulto , Carcinoma/fisiopatologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/fisiopatologia , Razão de Chances , Proteína 1 Complementadora Cruzada de Reparo de Raio-XAssuntos
Arilamina N-Acetiltransferase/genética , Carcinoma/genética , Citocromo P-450 CYP1A1/genética , Glutationa Transferase/genética , Isoenzimas/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo Genético/genética , Alelos , Biomarcadores Tumorais/genética , Carcinoma/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Marcadores Genéticos/genética , Genótipo , Glutationa S-Transferase pi , Humanos , Masculino , Neoplasias Nasofaríngeas/epidemiologia , Fatores de Risco , Estatística como Assunto , Taiwan/epidemiologiaRESUMO
BACKGROUND: Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC. METHODS: We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase I, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred. RESULTS: We found a consistent association between HLA-A*0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A*0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B*4601, which is in linkage disequilibrium with HLA-A*0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A*0207 and HLA-B*4601 (OR = 2.8, 95% CI = 1.7 to 4.4). Individuals homozygous for HLA-A*1101 had decreased risks for NPC (OR = 0.24, 95% CI = 0.13 to 0.46). The extended haplotype HLA-A*3303-B*5801/2-DRB1*0301-DQB1*0201/2-DPB1*0401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4). CONCLUSIONS: The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group.
Assuntos
Alelos , Povo Asiático/genética , Carcinoma/genética , Genes MHC da Classe II , Genes MHC Classe I , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Carcinoma/imunologia , Estudos de Casos e Controles , Feminino , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/imunologia , Razão de Chances , TaiwanRESUMO
Co-expression of B-cell leukemia-lymphoma 2 gene (Bcl-2) and Epstein-Barr virus latent membrane protein 1 (LMP-1) in nasopharyngeal carcinoma tissues were tested using immunohistochemical methods. Results showed that there were 32% (14/44) and 68% (30/44) LMP-1 and Bcl-2-positive cases, respectively. Among the LMP-1-positive tissues, 8 (57%) of 14 specimens were also Bcl-2-positive. The level of LMP-1 and Bcl-2 expression was associated with the clinical stages of nasopharyngeal carcinoma. Furthermore, when LMP-1- and Bcl-2-positive cases were combined, the highest positive score was found in clinical stage II as well as in the early stage (stages I and II) of nasopharyngeal carcinoma. While further studies with more cases are needed, this study suggests that co-expression of Bcl-2 and LMP-1 may be involved in the process of nasopharyngeal carcinoma aggravation.
Assuntos
Carcinoma/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas da Matriz Viral/metabolismo , Biópsia , Carcinoma/patologia , Carcinoma/virologia , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ , Mucosa/patologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas da Matriz Viral/genéticaRESUMO
Only three thyroid hormone receptor (TR) isoforms, alpha 1, beta 1, and beta 2, bind thyroid hormone (TH) and are considered to be true TRs. TR alpha 2, unable to bind TH, binds to TH response element on DNA and has been shown to exert dominant negative action on TR alpha1. TR alphas regulate many important processes such as proliferation, differentiation and apoptosis. To find out if TR alphas played roles in growth control of nasopharyngeal carcinoma cells, transfectant with inducible expression of TR alpha 1 was generated from NPC-TW 04 cell lines. Induced expression of TR alpha 1 in nasopharyngeal carcinoma cell reduced proliferation and colony-formation ability in agar. Tumor formation ability in nude mice was reduced in NPC cells with TR alpha 1 expression than those without expression or vector-transfected cells. Our results supported the hypothesis that TR alpha 1 functions as a tumor suppressor gene in nasopharyngeal carcinoma tumorigenesis.
Assuntos
Neoplasias Nasofaríngeas/genética , Receptores dos Hormônios Tireóideos/genética , Receptores alfa dos Hormônios Tireóideos , Animais , Apoptose , Diferenciação Celular , Divisão Celular , Humanos , Camundongos , Camundongos Nus , Neoplasias Nasofaríngeas/patologia , Fenótipo , Plasmídeos , Supressão Genética , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Induction of apoptosis of virus-infected cells is an important host cell defense mechanism. It is well documented that T cells may undergo apoptosis due to interactions between Fas and Fas ligand (FasL). In addition, signals that induce apoptosis in T cells can result from interaction of tumor necrosis factor (TNF)-alpha with TNF receptors (TNFRs). It has been shown that human T cell lines expressing HTLV-I have decreased sensitivity to Fas-mediated apoptosis. The susceptibility of HTLV-I-infected cells to TNF-alpha-induced apoptosis remains to be elucidated. In the present study, we examined the expression of TNFRs on HTLV-I-infected T cell lines that expressed T-cell activation markers and thus phenotypically resemble activated T cells. Different from primary activated T cells that expressed both TNFRs, none of the five HTLV-I-infected T cell lines studied had detectable TNFR1 and only three had TNFR2 on their cell surfaces, although, the RNA transcripts of both TNFR genes could be detected via reverse transcription-polymerase chain reaction in these cell lines. The T cell blasts, which we activated in vitro, were sensitive to apoptosis induced by TNF-alpha and by antibodies to TNFR1 and/or TNFR2. However, all of the HTLV-I-infected cell lines expressing TNFR2 were resistant to TNF-alpha-mediated apoptosis. These findings suggest that HTLV-I infection may interfere with the autonomous suicide programs of T cells, not only Fas/FasL but also TNFRs/TNF-alpha pathways, to prolong the life of the infected cells. This may contribute to viral persistence and favor survival and subsequent expansion of dysregulated infected T cells with the potential to produce HTLV-I-associated autoimmune-like diseases or malignancies.