Research Article

Lifetime history of alcohol consumption and K-ras mutations in pancreatic ductal adenocarcinoma

  1. Marta Crous-Bou1,2,3,
  2. Miquel Porta1,2,3,*,
  3. Tomàs López1,3,
  4. Manel Jariod4,
  5. Núria Malats1,5,
  6. Eva Morales1,3,
  7. Luisa Guarner2,6,
  8. Juli Rifà7,
  9. Alfredo Carrato8,
  10. Francisco X. Real1,5,9

Article first published online: 26 MAR 2009

DOI: 10.1002/em.20483

Issue

Environmental and Molecular Mutagenesis

Environmental and Molecular Mutagenesis

Volume 50, Issue 5, pages 421–430, June 2009

Additional Information

How to Cite

Crous-Bou, M., Porta, M., López, T., Jariod, M., Malats, N., Morales, E., Guarner, L., Rifà, J., Carrato, A. and Real, F. X. (2009), Lifetime history of alcohol consumption and K-ras mutations in pancreatic ductal adenocarcinoma. Environmental and Molecular Mutagenesis, 50: 421–430. doi: 10.1002/em.20483

Author Information

  1. 1

    Institut Municipal d'Investigació Mèdica, Barcelona, Spain

  2. 2

    Facultat de Medicina, Universitat Autònoma de, Barcelona, Spain

  3. 3

    CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

  4. 4

    Universitat Rovira i Virgili, Tarragona, Spain

  5. 5

    Centro Nacional de Investigaciones Oncológicas, Madrid, Spain

  6. 6

    Hospital Vall d'Hebron, Barcelona, Spain

  7. 7

    Hospital Son Dureta, Palma de Mallorca, Spain

  8. 8

    Hospital Universitario de Elche, Universidad Miguel Hernández, Alicante, Spain

  9. 9

    Universitat Pompeu Fabra, Barcelona, Spain

*Clinical & Molecular Epidemiology of Cancer Unit, Institut Municipal d'Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Carrer del Dr. Aiguader 88, E-08003 Barcelona, Catalonia, Spain

Publication History

  1. Issue published online: 3 JUN 2009
  2. Article first published online: 26 MAR 2009
  3. Manuscript Accepted: 22 JAN 2009
  4. Manuscript Received: 5 NOV 2008

Funded by

  • Generalitat de Catalunya. Grant Numbers: CIRIT SGR 0241, SGR 0078
  • Red Temática de Investigación Cooperativa de Centros en Cáncer. Grant Number: C03/10
  • Red Temática de Investigación Cooperativa de Centros en Epidemiología y Salud Pública. Grant Number: C03/09
  • U.S. National Cancer Institute (Use of the Serum Proteome on the Early Diagnosis of Malignant Biliary-Pancreatic Disease, Follow-up of the PANKRAS II Sub-cohort with Benign Pathology). Grant Number: 04-C-N272
  • CIBER de Epidemiología, Instituto de Salud Carlos III, Ministry of Health, Spain

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Keywords:

  • pancreatic ductal adenocarcinoma;
  • pancreatic neoplasm;
  • etiology;
  • alcohol drinking;
  • alcoholic beverages;
  • Ras genes

Abstract

Background:

In pancreatic ductal adenocarcinoma (PDA), evidence on the etiopathogenic role of alcohol consumption in the occurrence of K-ras mutations is scant, and the role of alcohol in pancreatic carcinogenesis is not well established. We analyzed the relation between lifetime consumption of alcohol and mutations in codon 12 of the K-ras oncogene in patients with PDA.

Methods:

Incident cases of PDA were prospectively identified and interviewed face-to-face during hospital admission about lifetime alcohol consumption and other lifestyle factors. Logistic regression was used to compare PDA cases (N = 107) with mutated and wild-type K-ras tumors (case–case study).

Results:

Mutated cases were moderate or heavy drinkers more frequently than wild-type cases: the odds ratio adjusted by age, sex, smoking, and history of pancreatitis (ORa) was 3.18 (95% confidence interval: 1.02–9.93; P = 0.046). Total grams of alcohol and years of consumption were higher in mutated than in wild-type cases: the ORa for lifetime alcohol consumption over 507,499 g was 3.35 (95% CI: 0.81–13.88); and for more than 40 years of alcohol consumption it was 4.47 (95% CI: 1.05–19.02). Age at onset of alcohol consumption and years of abstinence were also associated with the presence of K-ras mutations. There were no significant differences in alcohol dependency.

Conclusions:

Alcohol consumption is weakly associated with an increased risk of having a K-ras mutated PDA. To confirm or to refute the hypothesis that ethanol, acetaldehyde or other alcohol-related substances might influence the acquisition or persistence of K-ras mutations in the pancreatic epithelium, large and unselected studies are warranted. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc.

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