title: Insulin-like growth factors and insulin-like growth factor-binding proteins and prostate cancer risk: results from the prostate cancer prevention trial.
abstract: The role of the insulin-like growth factor (IGF) axis and whether IGFs interact with androgen-suppressing agents in relation to prostate carcinogenesis is unclear. This nested case-control study (n = 1,652 cases/1,543 controls) examined whether serum IGF1, IGF2, IGFBP2, IGFBP3, and the IGF1:IGFBP3 ratio were associated with prostate cancer in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Baseline serum was assayed for IGF-axis analytes using ELISA. Logistic regression estimated ORs and 95% confidence intervals for risk of total, low-grade (Gleason 2-6) and high-grade (Gleason 7-10) cancers. Results were stratified by intervention assignment. In both the placebo and finasteride arms, serum IGF1, IGF2, IGFBP3, and the IGF1:IGFBP3 ratio were not associated with prostate cancer. However, men in the highest versus lowest quartile of serum IGFBP2 had a 48% (P(trend) = 0.02) and 55% (P(trend) = 0.01) increased risk for total and low-grade cancers, respectively. These IGFBP2 associations were attenuated and no longer statistically significant in the finasteride arm. Our results suggest that in general, serum IGF-axis analytes were not associated with prostate cancer risk in the PCPT in which presence or absence of all cancers was biopsy-determined. The exception was the finding that high serum IGFBP2 is a risk factor for low-grade disease, which was attenuated for men on finasteride. Further research is needed to understand better the risk incurred by high IGFBP2 and whether androgen-suppressing agents such as finasteride influence aspects of IGFBP2 physiology relevant to prostate carcinogenesis.
authors: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA. mneuhous@fhcrc.org
authors: Marian L
authors: ML
authors: Neuhouser
authors: Elizabeth A
authors: EA
authors: Platz
authors: Cathee
authors: C
authors: Till
authors: Catherine M
authors: CM
authors: Tangen
authors: Phyllis J
authors: PJ
authors: Goodman
authors: Alan
authors: A
authors: Kristal
authors: Howard L
authors: HL
authors: Parnes
authors: Yuzhen
authors: Y
authors: Tao
authors: William D
authors: WD
authors: Figg
authors: M Scott
authors: MS
authors: Lucia
authors: Ashraful
authors: A
authors: Hoque
authors: Ann W
authors: AW
authors: Hsing
authors: Ian M
authors: IM
authors: Thompson
authors: Michael
authors: M
authors: Pollak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D016022:Case-Control Studies; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D012307:Risk Factors; D013002:Somatomedins / Q000032:analysis / Q000502:physiology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D018120:Finasteride