Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 34 (1), 55-62

K-ras Mutation and p16 and Preproenkephalin Promoter Hypermethylation in Plasma DNA of Pancreatic Cancer Patients: In Relation to Cigarette Smoking

Affiliations

K-ras Mutation and p16 and Preproenkephalin Promoter Hypermethylation in Plasma DNA of Pancreatic Cancer Patients: In Relation to Cigarette Smoking

Li Jiao et al. Pancreas.

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.

Figures

FIGURE 1
FIGURE 1
Examples of aberrant methylation of p16 and ppENK genes in plasma DNA of pancreatic cancer patients. m indicates methylated; MC, methylated allele control; NC, negative control, distilled water; um, unmethylated; UMC, unmethylated allele control.
FIGURE 2
FIGURE 2
Autoradiograph shows K-ras codon 12 mutations as detected by direct sequencing. Because plasma DNA contains normal DNA, the wild-type allele is present.

Similar articles

See all similar articles

Cited by 28 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback