title: Clinicopathologic distribution of KRAS and BRAF mutations in a Chinese population with colorectal cancer precursor lesions.
abstract: Investigating the clinical features and corresponding histomorphologic and molecular profiles of precursor lesions of colorectal cancer in a natural population provides new insights into the nature of colorectal cancer, uncovers new screening markers and establishes new prevention strategies for colorectal cancer. In this study, 4302 patients with at least one colorectal polyp from a large colorectal cancer screening program were evaluated and genetic mutations in either KRAS or BRAF were detected in 495 patients. The population-based mutation rates of KRAS and BRAF genes in colorectal polyps within this Chinese patient population were 21.8% and 12.1% respectively. Interestingly, considerable variability in the KRAS and BRAF mutations rates were found among different types of polyps. In a multivariate analysis, presence of villous histology and high-grade dysplasia was associated with KRAS mutations (OR, 3.0; 95% CI, 1.7-5.4 and OR, 3.5; 95% CI 1.9-6.5, respectively), while serrated adenomas and hyperplastic polyps were associated with BRAF V600E mutations (OR, 20.6; 95% CI, 8.2-51.8 and OR, 11.9; 95% CI 4.9-29.0, respectively). KRAS mutations may, in part, drive the histologic progression of adenomas toward a villous histology and higher grades of dysplasia. Mutant BRAF may, in part, drive the histologic progression of adenomas toward serrated histology. Dysplasia may arise from hyperplastic polyps, resulting in the formation of serrated adenomas and potentially the development of colorectal carcinoma.
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Chenghao
authors.initials: C
authors.lastname: Yi
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Department of Surgical Oncology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Pathology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; KRAS; colorectal cancer precursor lesions; conventional adenoma; serrated lesion