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


CONCLUSIONS
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.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland 21231, USA.
Mariana
M
Brait
Jean G
JG
Ford
Srinivas
S
Papaiahgari
Mary A
MA
Garza
Jin I
JI
Lee
Myriam
M
Loyo
Leonel
L
Maldonado
Shahnaz
S
Begum
Lee
L
McCaffrey
Mollie
M
Howerton
David
D
Sidransky
Mark R
MR
Emerson
Saifuddin
S
Ahmed
Carla D
CD
Williams
Mohammad Obaidul
MO
Hoque
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands / Q000235:genetics*; D003430:Cross-Sectional Studies; D056742:Cyclin D2 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D017491:Genes, APC; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009369:Neoplasms / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012307:Risk Factors; D015996:Survival Rate
C080336:CCND2 protein, human; D056742:Cyclin D2; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C533416:RARB2 protein, human; D018168:Receptors, Retinoic Acid; D019853:O(6)-Methylguanine-DNA Methyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi