RESUMO
BACKGROUND: MassARRAY (Agena Bioscience™) combines competitive PCR with MALDI-TOF mass spectrometry (MS) analysis that gives highly accurate, sensitive, and high-throughput methods for the quantitative analysis of variation of gene expression in multiple samples. SNPs (Single Nucleotide Polymorphisms) have a very high potential of discovering disease-gene relationships. SNP-genotyping through MassARRAY is not only a cost-effective genotyping method but also provides a platform to validate variants observed through a high-throughput Next-generation sequencing (NGS). METHODS: In the present study, we have incorporated the use of matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) as a tool for differentiating genotypes based on the mass of variant. We have performed multiplex PCR and genotyped 12 SNPs in 758 samples (166 cases and 592 controls). The 12 studied SNPs were chosen with a rationale for their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with esophageal cancer within the J&K population. Out of 12 SNPs, two SNPs rs12190287 of TCF21 and rs10046 of CYP19A1 were significantly associated with esophageal cancer with Odds Ratio (OR) 1.412 (1.09-1.8 at 95% CI, p = 0.008) and 1.54 (1.21-2.072 at 95% CI, p = 0.0007) within the population of Jammu and Kashmir. CONCLUSION: We explored 12 SNPs that were found to be associated with multiple cancers in literature with esophageal cancer within the population of J&K. This is the first study to find the relation of these SNPs with ESCC within the studied population. This study explores the relation of genetic and environmental factors with the ESCC susceptibility.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Ensaios de Triagem em Larga Escala/métodos , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Técnicas de Genotipagem/métodos , Voluntários Saudáveis , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
This study describes identification of p16(INK4A) sequence variants and their potential association with esophageal squamous cell carcinoma (ESCC) in a high risk population from Kashmir, India. We report a novel 7 base pair exon 2 deletion in 22 out of 106 (~20%) surgically resected tumor samples. The deletion beginning at the second base of codon 103, results in a frame shift causing premature termination of the protein at codon 142, with structural and functional consequences predicted by insilico analysis. The described mutation is a previously unreported variant of p16(INK4A), perhaps representing a founder mutation unique to the population.
Assuntos
Carcinoma de Células Escamosas/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Esofágicas/genética , População , Deleção de Sequência , Sequência de Bases , Quinase 6 Dependente de Ciclina/química , Análise Mutacional de DNA , Éxons , Efeito Fundador , Mutação da Fase de Leitura , Estudos de Associação Genética , Humanos , Índia , Modelos Moleculares , Ligação Proteica , Estrutura Secundária de Proteína , Fatores de Risco , Homologia Estrutural de Proteína , TermodinâmicaRESUMO
BACKGROUND: Leucine-rich repeat and fibronectin type 2 gene (LRFN2) variant rs2494938 has recently been found associated with esophageal cancer in a genome-wide association study in an Asian population. However, this association has not been replicated in any Indian population despite high incidence of the disease. MATERIALS AND METHODS: In the present case-control study, 166 cases and 459 controls were included. Taqman assay technique using real-time PCR was employed to investigate the association of the variant with esophageal cancer in the population of Jammu and Kashmir (J&K). The Hardy-Weinberg equilibrium for rs2494938 was assessed using the Chi-square test. The allele- and genotype-specific risk was estimated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: Variant rs2494938 was observed to be significantly associated with esophageal cancer with an allelic OR of 1.59 (1.23-2.04 at 95% CI, P = 0.0003). CONCLUSION: The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.