K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.
It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.
O'Brien
H
H
Institute of Food Research, Norwich Laboratory, Norwich Research Park, Colney, UK.
Matthew
J A
JA
Gee
J M
JM
Watson
M
M
Rhodes
M
M
Speakman
C T
CT
Stebbings
W S
WS
Kennedy
H J
HJ
Johnson
I T
IT
D000368:Aged; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004032:Diet; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008460:Meat; D008875:Middle Aged; D009092:Mucous Membrane / Q000166:cytology; D016133:Polymerase Chain Reaction; D012007:Rectum / Q000166:cytology*; D018570:Risk Assessment