TY - JOUR
T1 - Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics
AU - Einspahr, Janine G.
AU - Martinez, Maria Elena
AU - Jiang, Ruiyun
AU - Hsu, Chiu Hsieh
AU - Bhattacharrya, Achyut K.
AU - Ahnen, Dennis J.
AU - Jacobs, Elizabeth T.
AU - Houlihan, P. Scott
AU - Webb, C. Renee
AU - Alberts, David S.
AU - Hamilton, Stanley R.
PY - 2006/8
Y1 - 2006/8
N2 - In colorectal tumorigenesis, Ki-ras proto-oncogene mutation often occurs early in the adenoma-adenocarcinoma sequence, whereas mutation of the p53 gene is associated with late progression to carcinoma. We evaluated the relationship of demographic and clinicopathologic characteristics to Ki-ras mutation and p53 gene product overexpression in 1,093 baseline sporadic colorectal adenomas from 926 individuals enrolled in a phase III recurrence prevention trial. Ki-ras mutation was found in 14.7% of individuals and p53 overexpression was found in 7.0% of those tested. Multivariate analysis found older age, rectal location, and villous histology to be independently associated with Ki-ras mutation. Individuals with an advanced adenoma (≥1 cm or high-grade dysplasia or villous histology) had a 4-fold higher likelihood of Ki-ras mutation [odds ratios (OR), 3.96; 95% confidence intervals (CI), 2.54-6.18]. Ki-ras mutations in codon 12 and of the G-to-A transition type were more frequent in older individuals, whereas G-to-T transversion was more frequent in rectal adenomas than in the colon. Multivariate analysis showed that previous history of a polyp (P = 0.03) was inversely associated with p53 overexpression. Large adenoma size (≥1 cm), high-grade dysplasia, and villous histology were independently associated with p53 overexpression, with the strongest association for advanced adenomas (OR, 7.20; 95% CI, 3.01-17.22). Individuals with a Ki-ras mutated adenoma were more likely to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both alterations were classified as advanced (P ≤ 0.0001). Our large cross-sectional study supports the role of both Ki-ras and p53 in the progression of adenomas and shows that their molecular pathogenesis differs by anatomic location, age, and mucosal predisposition as evidenced by previous history of a polyp.
AB - In colorectal tumorigenesis, Ki-ras proto-oncogene mutation often occurs early in the adenoma-adenocarcinoma sequence, whereas mutation of the p53 gene is associated with late progression to carcinoma. We evaluated the relationship of demographic and clinicopathologic characteristics to Ki-ras mutation and p53 gene product overexpression in 1,093 baseline sporadic colorectal adenomas from 926 individuals enrolled in a phase III recurrence prevention trial. Ki-ras mutation was found in 14.7% of individuals and p53 overexpression was found in 7.0% of those tested. Multivariate analysis found older age, rectal location, and villous histology to be independently associated with Ki-ras mutation. Individuals with an advanced adenoma (≥1 cm or high-grade dysplasia or villous histology) had a 4-fold higher likelihood of Ki-ras mutation [odds ratios (OR), 3.96; 95% confidence intervals (CI), 2.54-6.18]. Ki-ras mutations in codon 12 and of the G-to-A transition type were more frequent in older individuals, whereas G-to-T transversion was more frequent in rectal adenomas than in the colon. Multivariate analysis showed that previous history of a polyp (P = 0.03) was inversely associated with p53 overexpression. Large adenoma size (≥1 cm), high-grade dysplasia, and villous histology were independently associated with p53 overexpression, with the strongest association for advanced adenomas (OR, 7.20; 95% CI, 3.01-17.22). Individuals with a Ki-ras mutated adenoma were more likely to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both alterations were classified as advanced (P ≤ 0.0001). Our large cross-sectional study supports the role of both Ki-ras and p53 in the progression of adenomas and shows that their molecular pathogenesis differs by anatomic location, age, and mucosal predisposition as evidenced by previous history of a polyp.
UR - http://www.scopus.com/inward/record.url?scp=33748032054&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748032054&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-06-0144
DO - 10.1158/1055-9965.EPI-06-0144
M3 - Article
C2 - 16896030
AN - SCOPUS:33748032054
SN - 1055-9965
VL - 15
SP - 1443
EP - 1450
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 8
ER -