K-ras Mutation, HPV Infection and Smoking or Alcohol Abuse Positively Correlate with Esophageal Squamous Carcinoma

[摘要] The Ras/Raf/MEK/ERK (MAPK) signal transduction cascade is an important mediator of a number of cellular fates including growth, survival and apoptosis. The aim of this study was to determine the incidence of B-raf, Kirsten-ras (K-ras) and Neuroblastoma-ras (N-ras) gene mutations in esophageal squamous cell carcinoma (ESCC) in the Greek population. DNA was extracted from 30 ESCC and 32 normal esophageal specimens and screened for V600E B-raf, and K-ras/N-ras codon 12 mutations, by PCR-RFLP based analysis. Among the genes tested, only the heterozygous K-ras mutation was detected in 5 out of the 30 ESCC specimens (16%), whereas no mutation was found in the normal esophageal tissue (P�?<�?0.022). The normal samples were screened negative for N-ras and V600E B-raf mutations. The increased risk of esophageal cancer was correlated with tobacco use (OR�?=�?3.5, P�?<�?0.023) and alcohol abuse (OR�?=�?7.22, P�?<�?0.001), accompanied with the high incidence of the k-ras codon 12 mutation (22%, OR�?=�?1.77 and 21%, OR�?=�?1.52), respectively. A similar positive association was seen in human papilloma virus (HPV)-infected patients (OR�?=�?5.66, P�?<�?0.003). Our overall findings demonstrate that the mutational activation of the K-ras gene, HPV infection and tobacco or alcohol abuse, can be considered independently or in combination as high risk factors for ESCC development.

[学科分类] 生理学与病理学

[关键词] N-ras