ArticleGut2007
Human colorectal mucosal O6-alkylguanine DNA-alkyltransferase activity and DNA-N7-methylguanine levels in colorectal adenoma cases and matched referents.
Article in Gut, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 21 citations in OpenAlex.
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsO(6)-alkylguanine DNA-alkyltransferase (MGMT) provides protection against alkylating agent-induced GC-->AT transition mutations. Such mutations are frequently seen in the KRAS oncogene of large colorectal adenomas, but whether adenoma or mutational risk in humans is influenced by MGMT activity and alkylating agent exposure is unclear. Hence, MGMT activity and, as an indicator of alkylating agent exposure, DNA-N7-methylguanine (N7-MeG) levels were determined in the normal tissue of patients with and without adenomas.
methodsBiopsy specimens of normal colorectal mucosa were collected during colonoscopy from 85 patients with histologically proved colorectal adenomas (cases) and from 85 patients free of gastrointestinal neoplasia (referents) matched by age, sex and biopsy location. MGMT activity and N7-MeG levels were measured in colorectal tissue extracts and DNA, respectively.
resultsMGMT activity was higher in the normal mucosa of cases than in referents (6.65+/-3.03 vs 5.61+/-2.74 fmol/micro g DNA, p = 0.01). On stratification of cases, MGMT activity was found to be considerably greater in the normal mucosa of cases with large adenomas (p = 0.003) and slightly higher in cases with a GC-->AT transition mutation in the K-ras gene (p = 0.03). Elevated MGMT levels were associated with an increased risk of adenoma (OR 1.17, 95% CI 1.03 to 1.33 per unit increase in activity). Detectable levels of N7-MeG were found in DNA from 89% of cases and 93% of referents, with levels ranging from <0.1 to 7.7 micro mol/mol dG. Cases and referents had similar DNA-N7-MeG levels.
conclusionsHuman exposure to methylating agents is widespread. MGMT activity is increased in the normal mucosa of patients with adenomas.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.