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

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Pathology & Oncology Research

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.

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Acknowledgments

We acknowledge Dr. Maria Tsardi for the supply of the esophageal specimens from the Pathology department of the University hospital in Heraklion, Crete, Greece.

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Authors and Affiliations

  1. Department of Virology, Medical School, University of Crete, P.O. Box 1527, Heraklion, 711 10, Crete, Greece

    Ioannis D. Lyronis, Stavroula Baritaki & Demetrios A. Spandidos

  2. Department of Otolaryngology, University Hospital of Crete, Heraklion, 712 01, Greece

    Ioannis Bizakis

  3. Department of Veterinary Medicine, University of Thessaly, Karditsa, Greece

    Elias Krambovitis

Authors
  1. Ioannis D. Lyronis
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  2. Stavroula Baritaki
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  3. Ioannis Bizakis
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  4. Elias Krambovitis
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  5. Demetrios A. Spandidos
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Correspondence to Demetrios A. Spandidos.

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Lyronis, I.D., Baritaki, S., Bizakis, I. et al. K-ras Mutation, HPV Infection and Smoking or Alcohol Abuse Positively Correlate with Esophageal Squamous Carcinoma. Pathol. Oncol. Res. 14, 267–273 (2008). https://doi.org/10.1007/s12253-008-9032-1

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  • DOI: https://doi.org/10.1007/s12253-008-9032-1

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