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 b etween 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). M ethods: Ki-ras mutations were detected by direct sequencing in 738 adenomat ous 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 person al 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 histol ogy (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.9 vs. tubula r), 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-ra s mutations to be independently associated with subject age (P = 0.01 for t rend), 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 independe ntly related to Ki-ras mutation. Conclusions: Ki-ras mutations are associat ed with the histologic features of adenoma progression (villous histology a nd high-grade dysplasia) rather than with adenoma growth.