TY - JOUR
T1 - Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk
AU - Huang, Wen Yi
AU - Su, L. Joseph
AU - Hayes, Richard B.
AU - Moore, Lee E.
AU - Katki, Hormuzd A.
AU - Berndt, Sonja I.
AU - Weissfeld, Joel L.
AU - Yegnasubramanian, Srinivasan
AU - Purdue, Mark P.
PY - 2012/11
Y1 - 2012/11
N2 - Background: Systematic genome-wide reductions of methylated cytosine (5-mC) levels have been observed in colorectal cancer tissue and are suspected to play a role in carcinogenesis, possibly as a consequence of inadequate folate intake. Reduced 5-mC levels in peripheral blood leukocytes have been associated with increased risk of colorectal cancer and adenoma in cross-sectional studies. Methods: To minimize disease- and/or treatment-related effects, we studied leukocyte 5-mC levels in prospectively collected blood specimens of 370 cases and 493 controls who were cancer-free at blood collection from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Leukocyte 5-mC level was determined by a high-pressure liquid chromatography (HPLC)/tandem mass spectrometry method and expressed as the relative amount of methyl to total cytosine residues, or %5-mC. We estimated the association between colorectal cancer risk and %5-mC categories by computing ORs and 95% confidence intervals (CI) through logistic regression modeling. Results: We observed no dose-dependent association between colorectal cancer and%5-mC categories (lowest vs. highest tertile: OR, 1.14; 95% CI, 0.80-1.63; Ptrend = 0.51). However, among subjects whose 5-mC levels were at the highest tertile, we observed an inverse association between natural folate intake and colorectal cancer (highest tertile of natural folate vs. lowest: OR, 0.35; 95% CI, 0.17-0.71; Ptrend = 0.003; Pinteraction = 0.003). Conclusions: This prospective investigation show no clear association between leukocyte 5-mC level and subsequent colorectal cancer risk but a suggestive risk modification between 5-mC level and natural folate intake. Impact: Adequate folate statusmayprotect against colorectal carcinogenesis through mechanisms involving adequate DNA methylation in the genome.
AB - Background: Systematic genome-wide reductions of methylated cytosine (5-mC) levels have been observed in colorectal cancer tissue and are suspected to play a role in carcinogenesis, possibly as a consequence of inadequate folate intake. Reduced 5-mC levels in peripheral blood leukocytes have been associated with increased risk of colorectal cancer and adenoma in cross-sectional studies. Methods: To minimize disease- and/or treatment-related effects, we studied leukocyte 5-mC levels in prospectively collected blood specimens of 370 cases and 493 controls who were cancer-free at blood collection from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Leukocyte 5-mC level was determined by a high-pressure liquid chromatography (HPLC)/tandem mass spectrometry method and expressed as the relative amount of methyl to total cytosine residues, or %5-mC. We estimated the association between colorectal cancer risk and %5-mC categories by computing ORs and 95% confidence intervals (CI) through logistic regression modeling. Results: We observed no dose-dependent association between colorectal cancer and%5-mC categories (lowest vs. highest tertile: OR, 1.14; 95% CI, 0.80-1.63; Ptrend = 0.51). However, among subjects whose 5-mC levels were at the highest tertile, we observed an inverse association between natural folate intake and colorectal cancer (highest tertile of natural folate vs. lowest: OR, 0.35; 95% CI, 0.17-0.71; Ptrend = 0.003; Pinteraction = 0.003). Conclusions: This prospective investigation show no clear association between leukocyte 5-mC level and subsequent colorectal cancer risk but a suggestive risk modification between 5-mC level and natural folate intake. Impact: Adequate folate statusmayprotect against colorectal carcinogenesis through mechanisms involving adequate DNA methylation in the genome.
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U2 - 10.1158/1055-9965.EPI-12-0700-T
DO - 10.1158/1055-9965.EPI-12-0700-T
M3 - Article
C2 - 23001241
AN - SCOPUS:84869231176
SN - 1055-9965
VL - 21
SP - 2014
EP - 2021
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 11
ER -