TY - JOUR
T1 - Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer
T2 - The Netherlands cohort study on diet and cancer
AU - Van Engeland, Manon
AU - Weijenberg, Matty P.
AU - Roemen, Guido M.J.M.
AU - Brink, Mirian
AU - De Bruïne, Adriaan P.
AU - Goldbohm, R. Alexandra
AU - Van den Brandt, Piet A.
AU - Baylin, Stephen B.
AU - De Goeij, Anton F.P.M.
AU - Herman, James G.
PY - 2003/6/15
Y1 - 2003/6/15
N2 - Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aherrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between promoter methylation of genes involved in CRC carcinogenesis and folate and alcohol intake was investigated. Methylation of the APC-1A, p14ARF, p16INK4A, hMLH1, O6-MGMT, and RASSF1A promoters was studied using methylation-specific PCR in 122 sporadic CRCs, derived from patients with folate and alcohol intake at either the lower or the higher quintiles of the distribution. Overall, promoter hypermethylation frequencies observed were: 39% for APC; 33% for p14ARF; 31% for p16INKA4A; 29% for hMLH1; 41% for O6-MGMT; and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter hypermethylation was higher in CRCs derived from patients with low folate/high alcohol intake (n = 61) when compared with CRCs from patients with high folate/low alcohol intake (n = 61), but the differences were not statistically significant. The number of CRCs with at least one gene methylated was higher (84%) in the low folate intake/high alcohol intake group when compared with the high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size limitations of this study, these data suggest that folate and alcohol intake may be associated with changes in promoter hypermethylation in CRC.
AB - Sporadic colorectal cancer (CRC) is characterized by genetic and epigenetic changes such as regional DNA hypermethylation and global DNA hypomethylation. Epidemiological and animal studies suggest that aherrant DNA methylation is associated with low dietary folate intake, which is aggravated by high alcohol intake. The relationship between promoter methylation of genes involved in CRC carcinogenesis and folate and alcohol intake was investigated. Methylation of the APC-1A, p14ARF, p16INK4A, hMLH1, O6-MGMT, and RASSF1A promoters was studied using methylation-specific PCR in 122 sporadic CRCs, derived from patients with folate and alcohol intake at either the lower or the higher quintiles of the distribution. Overall, promoter hypermethylation frequencies observed were: 39% for APC; 33% for p14ARF; 31% for p16INKA4A; 29% for hMLH1; 41% for O6-MGMT; and 20% for RASSF1A. For each of the tested genes, the prevalence of promoter hypermethylation was higher in CRCs derived from patients with low folate/high alcohol intake (n = 61) when compared with CRCs from patients with high folate/low alcohol intake (n = 61), but the differences were not statistically significant. The number of CRCs with at least one gene methylated was higher (84%) in the low folate intake/high alcohol intake group when compared with the high folate intake/low alcohol intake group (70%; P = 0.085). Despite the size limitations of this study, these data suggest that folate and alcohol intake may be associated with changes in promoter hypermethylation in CRC.
UR - http://www.scopus.com/inward/record.url?scp=0037731713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037731713&partnerID=8YFLogxK
M3 - Article
C2 - 12810640
AN - SCOPUS:0037731713
SN - 0008-5472
VL - 63
SP - 3133
EP - 3137
JO - Cancer Research
JF - Cancer Research
IS - 12
ER -