Hypermethylation of O6-methylguanine-DNA methyltransferase promoter may predict nonrecurrence after chemotherapy in colorectal cancer cases.
OBJECTIVE
Because O(6)-methylguanine-DNA methyltransferase (MGMT) plays an essential role in repairing DNA damage caused by environmental alkylating chemicals, we were interested in determining whether we could see any obvious changes in the properties of colorectal cancers (CRCs) in which the MGMT gene had been silenced by hypermethylation and hence in which very few MGMT protein molecules were being produced.


METHODS
We used a methylation-specific PCR assay to determine the methylation status of the MGMT promoter in the DNA molecules extracted from CRC and nontumor tissue samples from 116 patients who had undergone CRC surgery and for whom clinical outcome information was available on file.


RESULTS
We found evidence of MGMT promoter hypermethylation in 26 of 90 CRC cases, and we noted that the later the stage at which a tumor was diagnosed, the less likely its MGMT promoter was to be methylated (P = 0.03, adjusting for chemotherapy), especially for stage D patients (P = 0.01). We also found that CRC patients with unmethylated MGMT promoters were much more likely to experience recurrence within 36 months than patients with hypermethylated MGMT promoters (crude odds ratio, 14.0; 95% confidence interval, 2.42-81.01). After adjustment for stage, CRC patients with unmethylated MGMT promoters who had been exposed to chemotherapy were found to have a 5.3-fold greater risk of recurrence than those who had no exposure to chemotherapy (95% confidence interval, 1.15-30.92).


CONCLUSIONS
Hypermethylation of the MGMT promoter may be predictive of a low risk of recurrence in CRC patients receiving adjuvant chemotherapy.
Nagasaka
Takeshi
T
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Sharp
Gerald B
GB
Notohara
Kenji
K
Kambara
Takeshi
T
Sasamoto
Hiromi
H
Isozaki
Hiroshi
H
MacPhee
Donald G
DG
Jass
Jeremy R
JR
Tanaka
Noriaki
N
Matsubara
Nagahide
N
D000368:Aged; D003106:Colon / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012007:Rectum / Q000201:enzymology
D019853:O(6)-Methylguanine-DNA Methyltransferase