RESUMEN
This study investigated the association of seven widely known DNA repair gene polymorphisms (hOGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPC Val499Ala, XPD Lys751Gln and ERCC1 Cys8092Ala) with dietary and environmental factors for Nasopharyngeal Carcinoma (NPC) susceptibility in Nagaland of Northeast India. The genotypes were determined in 128 NPC patients and 180 healthy controls by PCR-RFLP. XRCC1 Arg280His, XPC Val499Ala and ERCC1 Cys8092Ala were found to be associated with NPC risk. Tobacco smoking and burning of firewood for cooking were also found to be a risk factor for NPC. The haplotype analysis of five single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPD Lys751Gln and ERCC1 Cys8092Ala identified haplotype TGAAC to be significantly associated with NPC. Multifactor dimensionality reduction (MDR) analysis suggested ERCC1 Cys8092Ala to be the best one-factor model that could predict NPC risk. From this study, we conclude that examining the synergistic interactions of various gene-environmental factors together is a better approach to understand NPC susceptibility, instead of their individual effects.
Asunto(s)
Dieta , Predisposición Genética a la Enfermedad , Exposición por Inhalación , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo de Nucleótido Simple , Ventilación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Culinaria , Reparación del ADN/genética , Femenino , Estudios de Asociación Genética , Haplotipos , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
During Hepatitis B virus infection, the pathogen sensors Toll-like receptors (TLRs) play a role in innate immunity system. The study aimed to investigate mRNA expression levels of TLR2 and TLR3 in Hepatitis B virus (HBV) mediated chronic hepatitis B (CHB), cirrhosis (CIRR), and hepatocellular carcinoma (HCC), and to correlate viral load with severity of these diseases and expression of TLRs. A total of 180 HBV DNA positive samples were selected for the study. HVB-DNA was detected by multiplex PCR. Viral load estimation was done by using the Ampisure HBV Quantitative kit as per manufacture instructions. Expression levels of TLR2 and TLR3 were determined by real time PCR. The viral load was estimated to be 6.64log10 IU/ml in CHB, 4.88log10 IU/ml in CIRR, and 4.86log10 IU/ml in HCC. No significant association of viral load was found with increasing age. Upregulation of TLR2 expression in CHB when individually compared with CIRR and HCC was found to be statistically significant. Downregulation of TLR3 expressions in CIRR when compared to both CHB and HCC individually were found to be statistically significant. No significant effect of viral load on the expression of TLR2 and 3 were found. With severity of the disease from CHB to HCC, the HBV load decreases. The study suggests the possibility of HBV interacting with signalling of both analysed TLR receptors which partially explains the induction of immune tolerance pathways by Hepatitis B virus. J. Med. Virol. 89:1008-1014, 2017. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Carcinoma Hepatocelular/virología , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Receptor Toll-Like 2/biosíntesis , Receptor Toll-Like 3/biosíntesis , Carga Viral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/inmunología , Femenino , Perfilación de la Expresión Génica , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/inmunología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/inmunología , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Toll-Like 2/análisis , Receptor Toll-Like 2/genética , Receptor Toll-Like 3/análisis , Receptor Toll-Like 3/genética , Adulto JovenRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin. OBJECTIVES: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types. MATERIALS AND METHODS: A total of 40 formalinfixed, paraffinembedded NPC biopsy samples and tissues from 20 healthy controls were collected to study the expression level of EBNA1 and LMP1 using immunohistochemistry. RESULTS: EBNA1 and LMP1 expression was found in 92.5% and 90% respectively, of the cases and none of the control specimens. The expression patterns of EBNA1 and LMP1 were determined to be statistically significant (p<0.05) when correlated with sex, age and histological distributions. Also immunohistochemistry was found to be a sensitive technique in the detection of EBV. CONCLUSIONS: The study reveals that the potent oncoproteins EBNA1 and LMP1 were over expressed in our population cohort. Our findings are to some extent inconsistent with earlier reports as our population showed a higher expression of both EBNA1 and LMP1 compared to other studies.