Faculty Collaboration Database

K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma DNA of pancreatic cancer patients: in relation to cigarette smoking. Pancreas 2007 Jan;34(1):55-62

Date

01/02/2007

Pubmed ID

17198183

Pubmed Central ID

PMC1905887

DOI

10.1097/01.mpa.0000246665.68869.d4

Scopus ID

2-s2.0-33846017682 (requires institutional sign-in at Scopus site)   74 Citations

Abstract

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.

Author List

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

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adult
Aged
DNA Methylation
Enkephalins
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Genes, p16
Genes, ras
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Mutation
Pancreatic Neoplasms
Promoter Regions, Genetic
Protein Precursors
Smoking