K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma DNA of pancreatic cancer patients: in relation to cigarette smoking.

Published

Journal Article

OBJECTIVES: To examine the profiles of K-ras mutations and p16 and preproenkephalin (ppENK) promoter hypermethylation and their associations with cigarette smoking in pancreatic cancer patients. METHODS: In plasma DNA of 83 patients with untreated primary pancreatic ductal adenocarcinoma, DNA hypermethylation was determined by methylation-specific polymerase chain reaction and K-ras codon 12 mutations by enriched-nested polymerase chain reaction followed by direct sequencing. Information on smoking exposure was collected by in-person interview. Pearson chi test and Fisher exact test were used in statistical analysis. RESULTS: K-ras mutations, ppENK, and p16 promoter hypermethylation were detected in 32.5%, 29.3%, and 24.6% of the patients, respectively. Sixty-three percent (52/83) of patients exhibited at least one of the alterations. Smoking was associated with the presence of K-ras mutations (P = 0.003). A codon 12 G-to-A mutation was predominantly observed in regular smokers and in heavy smokers (pack-year of smoking > or =36). Smoking was not associated with p16 or ppENK hypermethylation. CONCLUSIONS: These preliminary observations suggest that plasma DNA might be a useful surrogate in detecting genetic and epigenetic alterations of pancreatic cancer. The findings on the association between K-ras mutation and smoking were in consistency with previous studies. Further studies on environmental modulators of epigenetic changes in pancreatic cancer are warranted.

Full Text

Duke Authors

Cited Authors

  • Jiao, L; Zhu, J; Hassan, MM; Evans, DB; Abbruzzese, JL; Li, D

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 55 - 62

PubMed ID

  • 17198183

Pubmed Central ID

  • 17198183

Electronic International Standard Serial Number (EISSN)

  • 1536-4828

Digital Object Identifier (DOI)

  • 10.1097/01.mpa.0000246665.68869.d4

Language

  • eng

Conference Location

  • United States