Association between lifestyle factors and CpG island methylation in a cancer-free population

Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2984-91. doi: 10.1158/1055-9965.EPI-08-1245. Epub 2009 Oct 27.

Abstract

Background: Many risk factors have been associated with cancer, such as age, family history, race, smoking, high-fat diet, and poor nutrition. It is important to reveal the molecular changes related to risk factors that could facilitate early detection, prevention, and overall control of cancer.

Methods: We selected six cancer-specific methylated genes that have previously been reported in primary tumors and have also been detected in different bodily fluids of cancer patients. Here, we used quantitative fluorogenic real-time methylation-specific PCR in plasma DNA samples for the detection of methylation changes from an asymptomatic population who do not have any known cancer.

Results: The promoter methylation frequencies of the studied genes were as follows: APC (7%), CCND2 (22%), GSTP1 (2%), MGMT (9%), RARbeta2 (29%), and P16 (3%). Promoter methylation of at least one of the genes analyzed was observed in approximately 46% (72 of 157) of the samples by binary dichotomization. Promoter hypermethylation of at least two genes was detected in 17% (26 of 157) of the samples. RARbeta2 methylation was observed in 45% of subjects who had a high-fat diet in contrast with those who had a low-fat diet (23%; P = 0.007).

Discussion: Our findings may help to elucidate early methylation changes that may lead to cancer development. These methylation changes could be due to exposure to risk factors and may be useful for cancer prevention measures such as changes in lifestyle. Longitudinal follow-up of a high-risk population is needed to understand the association of methylation of candidate genes in cancer development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CpG Islands / genetics*
  • Cross-Sectional Studies
  • Cyclin D2 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation*
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics
  • Genes, APC
  • Glutathione S-Transferase pi / genetics
  • Humans
  • Life Style*
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Neoplasms / genetics*
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Receptors, Retinoic Acid / genetics
  • Risk Factors
  • Survival Rate

Substances

  • CCND2 protein, human
  • Cyclin D2
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • Neoplasm Proteins
  • RARB2 protein, human
  • Receptors, Retinoic Acid
  • O(6)-Methylguanine-DNA Methyltransferase
  • GSTP1 protein, human
  • Glutathione S-Transferase pi