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

Background & Aims: 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. GASTROENTEROLOGY 2001;121:302-309