Promoter hypermethylation of tumor-related genes in sporadic colorectal cancer in young patients.
Sporadic colorectal cancer (SCRC) occurring in young patients represent a subset with a higher proportion of advanced tumors and a poor prognosis, however, the genetic basis of SCRCs has not yet been sufficiently studied. We assigned 16 SCRC patients aged 40 years or less to group 1, and 30 SCRCs patients aged 65 years or more to group 2. The methylation status in the promoter of 7 tumor suppressor genes regarding these two groups was then examined. The average number of hypermethylated tumor-related genes per sample in group 1 was 1.50 +/- 0.07, which was significantly lower than that in group 2 of 2.73 +/- 1.24 (p = 0.0040). The frequencies of the promoter hypermethylation of hMLH1, p15INK4b, p16INK4a, and RASSF1A in group 1 were 12.5%, 12.5%, 12.5%, 6.3%, and 0.0%, which were substantially less frequent than those same rates observed in group 2. In contrast, the frequencies of the promoter hypermethylation of APC, MGMT, p14ARF, in group 1 were 43.8%, 37.5%, and 31.3%, which were as frequent as those seen in group 2. The promoter hypermethylation of APC, MGMT, and pl4ARF is therefore considered to be closely related to the development of SCRCs in young patients, regardless of aging.
Noda
H
H
Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan. noda164@omiya.jichi.ac.jp
Mashima
R
R
Kamiyama
H
H
Okada
S
S
Kawamura
Y J
YJ
Konishi
F
F
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D050762:Cyclin-Dependent Kinase Inhibitor p15; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000070957:MutL Protein Homolog 1