Ki-ras proto-oncogene mutations in sporadic colorectal adenomas: relationship to histologic and clinical characteristics

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 121; no. 2; p. 302
• Main Authors: Maltzman, T, Knoll, K, Martinez, M E, Byers, T, Stevens, B R, Marshall, J R, Reid, M E, Einspahr, J, Hart, N, Bhattacharyya, A K, Kramer, C B, Sampliner, R, Alberts, D S, Ahnen, D J
• Format: Journal Article
• Language: English
• Published: United States 01.08.2001
• Subjects: Adenoma - genetics; Adenoma - pathology; Aged; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Mutational Analysis; Female; Genes, ras - genetics; Genetic Predisposition to Disease; Humans; Male; Mutation; Neoplasm Recurrence, Local; Prevalence
• ISSN: 0016-5085
• DOI: 10.1053/gast.2001.26278

[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). 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. 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. Ki-ras mutations are associated with the histologic features of adenoma progression (villous histology and high-grade dysplasia) rather than with adenoma growth.