RESUMO
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.
Assuntos
Dieta , Predisposição Genética para Doença , Exposição por Inalação , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Ventilação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Culinária , Reparo do DNA/genética , Feminino , Estudos de Associação Genética , Haplótipos , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Interleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters and patient survival. METHODS: Expression analysis was performed by Real time quantitative polymerase chain reaction and receiver operating characteristic (ROC) curve analysis was done. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed. RESULTS: IL8 expression showed upregulation in tissue (p = 0.000) and blood samples (p = 0.481), IL12 expression showed downregulation in tissue samples (p = 0.064) and upregulation in blood samples (p = 0.689) and IL13 expression showed upregulation in tissue (p = 0.000) and blood samples (p = 0.006). IL13 expression in tissue showed the highest area under the curve (AUC) value (0.773) for ESCC diagnosis, followed by IL8 expression in tissue (0.704) and IL13 expression in blood (0.643). This study also reveals the correlation of studied cytokines in tissue and blood level. Different clinicopathological and dietary factors showed significant association (p < 0.05) with IL8, IL12 and IL13 expression and with survival of ESCC patients. IL8 expression in blood and IL12 expression in tissue and blood showed significant association (p < 0.05) with patient survival. CONCLUSION: Altered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ESCC screening. Additionally, both survival and hazard analysis data indicate the effects of different parameters on the prognosis of ESCC patients.
Assuntos
Biomarcadores Tumorais , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Interleucina-12 , Interleucina-13 , Interleucina-8 , Humanos , Masculino , Biomarcadores Tumorais/metabolismo , Prognóstico , Feminino , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Pessoa de Meia-Idade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Interleucina-8/metabolismo , Interleucina-13/metabolismo , Interleucina-13/sangue , Interleucina-12/metabolismo , Interleucina-12/sangue , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
HLA-C*08:01:01:05 differs from HLA-C*08:01:01:02 by one nucleotide deletion (T > -) at position 674 in intron 2.
Assuntos
Antígenos HLA-C , Polimorfismo de Nucleotídeo Único , Alelos , Antígenos HLA-C/genética , Humanos , Índia , Íntrons/genéticaRESUMO
A single nucleotide change (C to T) in HLA-DQB1*01:03:01:03 results in the novel allele, HLA-DPA1*01:03:01:21.
Assuntos
Cadeias alfa de HLA-DP , Alelos , Cadeias alfa de HLA-DP/genética , Humanos , ÍndiaRESUMO
One nucleotide substitution (C > G) in 3'-UTR of HLA-C*04:01:01:01 results in the novel allele, HLA-C*04:01:01:78.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Alelos , Antígenos HLA-C/genética , Humanos , ÍndiaRESUMO
A single nucleotide change in HLA-DPA1*01:03:01:01 results in the novel null allele, HLA-DPA1*01:29N.
Assuntos
Cadeias alfa de HLA-DP , Alelos , Cadeias alfa de HLA-DP/genética , Humanos , ÍndiaRESUMO
One nucleotide substitution (C>T) in intron 1 of HLA-C*03:04:01:02 results in the novel allele, HLA-C*03:04:01:38.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Alelos , Antígenos HLA-C/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Índia , Íntrons/genéticaRESUMO
HLA-DQB1*05:03:01:04 differs from HLA-DQB1*05:03:01:01 by one nucleotide substitution at position 5075 (A>G).
Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Humanos , ÍndiaRESUMO
HLA-DQB1*03:01:01:07, intron 1 [1217(AâG)] and intron 2 [2138 (TâC)] substitutions generate HLA-DQB1*03:01:01:23 and HLA-DQB1*03:01:01:24, respectively.
Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Humanos , Índia , Íntrons/genéticaRESUMO
One nucleotide substitution (G>A) in codon 41 of HLA-C*04:03:01:01 results in the novel allele, HLA-C*04:400.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Alelos , Códon , Antígenos HLA-C/genética , Humanos , ÍndiaRESUMO
One nucleotide substitution (C>T) in codon 228 of HLA-C*04:06:01 results in the novel allele, HLA-C*04:06:03.
Assuntos
Antígenos HLA-C , Mutação Silenciosa , Alelos , Códon , Antígenos HLA-C/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , ÍndiaRESUMO
One nucleotide substitution (A>T) in intron 1 of HLA-DPA1*02:01:01:02 results in the novel allele, HLA-DPA1*02:01:01:12.
Assuntos
Cadeias alfa de HLA-DP , Alelos , Cadeias alfa de HLA-DP/genética , Humanos , Índia , Íntrons/genéticaRESUMO
One nucleotide substitution in codon 127 of HLA-DQB1*03:01:01:07 results in the novel allele, HLA-DQB1*03:404.
Assuntos
Alelos , Éxons/genética , Cadeias beta de HLA-DQ/genética , Humanos , ÍndiaRESUMO
A single nucleotide change (T to C) in HLA-B*15:02:01:01 results in the novel allele, HLA-B*15:02:01:04.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Alelos , Antígenos HLA-B/genética , Humanos , ÍndiaRESUMO
Thirteen nucleotide substitutions in intron 1 of HLA-DPA1*02:01:01:09 results in a novel allele, HLA-DPA1*02:01:01:13.
Assuntos
Cadeias alfa de HLA-DP , Alelos , Cadeias alfa de HLA-DP/genética , Humanos , Índia , Íntrons/genéticaRESUMO
Two nucleotide changes in the 3'untranslated region of HLA-C*07:06:01:01 results in the novel allele, HLA-C*07:06:01:06.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Alelos , Frequência do Gene , Antígenos HLA-C/genética , Humanos , ÍndiaRESUMO
Two nucleotide changes in the 3'-UTR of HLA-C*07:02:01:01 results in the novel allele, HLA-C*07:02:01:97.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Alelos , Frequência do Gene , Antígenos HLA-C/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , ÍndiaRESUMO
A single nucleotide change (C to T) in HLA-B*38:02:01 results in the novel allele, HLA-B*38:02:01:02.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Alelos , Antígenos HLA-B/genética , Humanos , ÍndiaRESUMO
One nucleotide change (G>A) at intron 1 of HLA-A*11:01:01:01 results in the novel allele, HLA-A*11:01:01:25.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Antígeno HLA-A11/genética , Polimorfismo de Nucleotídeo Único , Alelos , Povo Asiático/etnologia , Estudos de Coortes , Frequência do Gene , Humanos , Índia/etnologia , ÍntronsRESUMO
A single nucleotide change (G to T) in HLA-B*13:01:01:01 results in the novel allele, HLA-B*13:01:01:03.