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

Marta Crous-Bou, Miquel Porta, Tomàs López, Manel Jariod, Ńuria Malats, Eva Morales, Luisa Guarner, Juli Rifà, Alfredo Carrato, Francisco X. Real

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9 Citations (Scopus)

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 5 107) with mutated and wildtype 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 5 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. © 2009 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)421-430
JournalEnvironmental and Molecular Mutagenesis
Volume50
Issue number5
DOIs
Publication statusPublished - 1 Jun 2009

Keywords

  • Alcohol drinking
  • Alcoholic beverages
  • Etiology
  • Pancreatic ductal adenocarcinoma
  • Pancreatic neoplasm
  • Ras genes

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