title: K-ras mutation, HPV infection and smoking or alcohol abuse positively correlate with esophageal squamous carcinoma.
abstract: 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.
authors.affiliation: Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
authors.forename: Ioannis D
authors.initials: ID
authors.lastname: Lyronis
authors.forename: Stavroula
authors.initials: S
authors.lastname: Baritaki
authors.forename: Ioannis
authors.initials: I
authors.lastname: Bizakis
authors.forename: Elias
authors.initials: E
authors.lastname: Krambovitis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006115:Greece; D006801:Humans; D008297:Male; D019083:Mediterranean Region; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D030361:Papillomavirus Infections; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking
chemical_list: D048493:Proto-Oncogene Proteins B-raf