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.
Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom. andrew.roddam@ceu.ox.ac.uk
Andrew W
AW
Roddam
Naomi E
NE
Allen
Paul
P
Appleby
Timothy J
TJ
Key
Luigi
L
Ferrucci
H Ballentine
HB
Carter
E Jeffrey
EJ
Metter
Chu
C
Chen
Noel S
NS
Weiss
Annette
A
Fitzpatrick
Ann W
AW
Hsing
James V
JV
Lacey
Kathy
K
Helzlsouer
Sabina
S
Rinaldi
Elio
E
Riboli
Rudolf
R
Kaaks
Joop A M J L
JA
Janssen
Mark F
MF
Wildhagen
Fritz H
FH
Schröder
Elizabeth A
EA
Platz
Michael
M
Pollak
Edward
E
Giovannucci
Catherine
C
Schaefer
Charles P
CP
Quesenberry
Joseph H
JH
Vogelman
Gianluca
G
Severi
Dallas R
DR
English
Graham G
GG
Giles
Pär
P
Stattin
Göran
G
Hallmans
Mattias
M
Johansson
June M
JM
Chan
Peter
P
Gann
Steven E
SE
Oliver
Jeff M
JM
Holly
Jenny
J
Donovan
François
F
Meyer
Isabelle
I
Bairati
Pilar
P
Galan
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