Circulating insulin-like growth factor II and colorectal adenomas.
Circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be risk factors for the development of colorectal cancer. On the other hand, IGF-II and IGFBP-2 are overexpressed in colorectal carcinomas. These contrasting backgrounds led us to investigate the relationship between serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and the presence of colorectal adenomas, known precursors of colorectal carcinoma, in 345 volunteers attending a screening flexible sigmoidoscopy trial (entry criteria: healthy, aged 55-64 yr). The most striking finding was an elevated mean serum IGF-II in individuals with adenomas (n = 52) compared with controls (mean difference, 139 ng/mL; 95% confidence intervals, 82, 196; P < 0.0001). Logistic regression adjusting for confounding factors confirmed the significant association between IGF-II and adenoma occurrence (P < 0.0001) and revealed an additional positive association with serum IGFBP-2 (P < 0.0001). However, there was no association found between either serum IGF-I and/or IGFBP-3 and the presence of adenomas. Additionally, in 31 individuals with adenomas in whom levels were determined pre- and postpolypectomy, there was a significant fall in mean IGF-II (P < 0.001) and IGFBP-2 (P < 0.001) after adenoma removal, but no difference in IGF-II and IGFBP-2 concentrations between repeated samples in 20 individuals without adenomas. Immunohistochemical studies demonstrated IGF-II expression in 83% of all adenomas, which contrasted with absent expression in normal colonic expression and hyperplastic polyps. This study has shown for the first time that serum IGF-II may be a tumor marker in individuals with colorectal adenomas. Further studies are needed to validate these relationships in larger populations, including individuals undergoing colonoscopy.
Renehan
A G
AG
Department of Surgery, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Painter
J E
JE
O'Halloran
D
D
Atkin
W S
WS
Potten
C S
CS
O'Dwyer
S T
ST
Shalet
S M
SM
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012812:Sigmoidoscopy
D014408:Biomarkers, Tumor; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II