Genomic methylation of leukocyte DNA in relation to colorectal adenoma among asymptomatic women.
OBJECTIVE
Systemic inhibition of DNA methylation causes cancers in animals, in part by inducing genetic instability. Epidemiologic evidence linking low genomic methylation in systemic blood DNA to carcinogenesis is limited, however, specifically to the colorectum, in which genetic instability is a primary etiologic factor. We examined genomic methylation of leukocyte DNA in relation to colorectal adenoma (CRA) among asymptomatic women (40-79 years of age) participating in a multicenter colonoscopy screening study (CONCeRN Study, 2000-2002).


METHODS
Of all participants who completed self-administered risk factor and food frequency questionnaires, peripheral blood donation, and colonoscopy, 115 pairs of CRA cases and controls with matching age and month of blood draw were studied. Genomic methylation of leukocyte DNA was determined by liquid chromatography mass spectrometry. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).


RESULTS
Compared with women in the lowest tertile of genomic methylation, women in the second (OR, 0.72; 95% CI: 0.34-1.52) and third tertiles (OR, 0.17; 95% CI: 0.06-0.49) had lower risk of CRA (P trend = .002). The inverse relationship was stronger for nonadvanced than for advanced adenoma and, less notably, for proximal than for distal adenoma. The association was also moderately more protective with low rather than high total folate intake but did not differ by other nutrients involved in 1-carbon metabolism or colorectal cancer risk factors.


CONCLUSIONS
Our findings regarding asymptomatic CRA implicate systemic genomic methylation as a potential etiologic factor for an early stage of CRA.
Lim
Unhee
U
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland, USA.
Flood
Andrew
A
Choi
Sang-Woon
SW
Albanes
Demetrius
D
Cross
Amanda J
AJ
Schatzkin
Arthur
A
Sinha
Rashmi
R
Katki
Hormuzd A
HA
Cash
Brooks
B
Schoenfeld
Phillip
P
Stolzenberg-Solomon
Rachael
R
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008019:Life Style; D008875:Middle Aged; D009752:Nutritional Status; D012307:Risk Factors; D014481:United States