Ki-ras proto-oncogene mutations in sporadic colorectal adenomas: relationship to histologic and clinical characteristics.
OBJECTIVE
[corrected] The goal of this study was to examine the relationship between Ki-ras mutations in colorectal adenomas and characteristics of both the subject (age, gender, and family/personal history of colonic neoplasia) and the adenoma (multiplicity, size, location, and histologic features).


METHODS
Ki-ras mutations were detected by direct sequencing in 738 adenomatous polyps removed at baseline from 639 participants in a nutritional trial of adenoma recurrence.


RESULTS
Ki-ras mutations were detected in 17.2% of the adenomas. Ki-ras mutations were unrelated to gender, family, or personal history of colonic neoplasia, location within the colorectum, or adenoma multiplicity, but were more common in older subjects (P = 0.01 for trend), in larger adenomas (P < 0.0001 for trend), in adenomas with villous histology (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.9 vs. tubular), and in adenomas with high-grade dysplasia (32.0% vs. 13.6%; OR, 3.0; 95% CI, 1.9-4.6 vs. low-grade dysplasia). Multivariate analysis showed Ki-ras mutations to be independently associated with subject age (P = 0.01 for trend), tubulovillous/villous histology (OR, 2.3; 95% CI, 1.5-3.7), and high-grade dysplasia (OR, 1.9; 95% CI, 1.2-3.1). Adenoma size was not independently related to Ki-ras mutation.


CONCLUSIONS
Ki-ras mutations are associated with the histologic features of adenoma progression (villous histology and high-grade dysplasia) rather than with adenoma growth.
Maltzman
T
T
Department of Veterans Affairs Medical Center, 111E, 1055 Clermont Street, Denver, Colorado 80220, USA.
Knoll
K
K
Martinez
M E
ME
Byers
T
T
Stevens
B R
BR
Marshall
J R
JR
Reid
M E
ME
Einspahr
J
J
Hart
N
N
Bhattacharyya
A K
AK
Kramer
C B
CB
Sampliner
R
R
Alberts
D S
DS
Ahnen
D J
DJ
D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D015995:Prevalence; D000090063:Proto-Oncogene Mas