Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies.
BACKGROUND
Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer.


OBJECTIVE
To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.


METHODS
Studies identified in PubMed, Web of Science, and CancerLit.


METHODS
The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate.


METHODS
Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom.


RESULTS
The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.


CONCLUSIONS
Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies.


CONCLUSIONS
High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.
Roddam
Andrew W
AW
Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. andrew.roddam@ceu.ox.ac.uk
Allen
Naomi E
NE
Appleby
Paul
P
Key
Timothy J
TJ
Ferrucci
Luigi
L
Carter
H Ballentine
HB
Metter
E Jeffrey
EJ
Chen
Chu
C
Weiss
Noel S
NS
Fitzpatrick
Annette
A
Hsing
Ann W
AW
Lacey
James V
JV
Helzlsouer
Kathy
K
Rinaldi
Sabina
S
Riboli
Elio
E
Kaaks
Rudolf
R
Janssen
Joop A M J L
JA
Wildhagen
Mark F
MF
Schröder
Fritz H
FH
Platz
Elizabeth A
EA
Pollak
Michael
M
Giovannucci
Edward
E
Schaefer
Catherine
C
Quesenberry
Charles P
CP
Vogelman
Joseph H
JH
Severi
Gianluca
G
English
Dallas R
DR
Giles
Graham G
GG
Stattin
Pär
P
Hallmans
Göran
G
Johansson
Mattias
M
Chan
June M
JM
Gann
Peter
P
Oliver
Steven E
SE
Holly
Jeff M
JM
Donovan
Jenny
J
Meyer
François
F
Bairati
Isabelle
I
Galan
Pilar
P
D000368:Aged; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood*; D012307:Risk Factors; D013002:Somatomedins / Q000378:metabolism*
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II