Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies.
Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.
Rinaldi
Sabina
S
International Agency for Research on Cancer, Lyon, France.
Cleveland
Rebecca
R
Norat
Teresa
T
Biessy
Carine
C
Rohrmann
Sabine
S
Linseisen
Jakob
J
Boeing
Heiner
H
Pischon
Tobias
T
Panico
Salvatore
S
Agnoli
Claudia
C
Palli
Domenico
D
Tumino
Rosario
R
Vineis
Paolo
P
Peeters
Petra H M
PH
van Gils
Carla H
CH
Bueno-de-Mesquita
Bas H
BH
Vrieling
Alina
A
Allen
Naomi E
NE
Roddam
Andrew
A
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Manjer
Jonas
J
Borgquist
Signe
S
Dumeaux
Vanessa
V
Torhild Gram
Inger
I
Lund
Eiliv
E
Trichopoulou
Antonia
A
Makrygiannis
Georgios
G
Benetou
Vassiliki
V
Molina
Esther
E
Donate Suárez
Ignacio
I
Barricarte Gurrea
Aurelio
A
Gonzalez
Carlos A
CA
Tormo
Maria-Jose
MJ
Altzibar
Jone M
JM
Olsen
Anja
A
Tjonneland
Anne
A
Grønbaek
Henning
H
Overvad
Kim
K
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Morois
Sophie
S
Slimani
Nadia
N
Boffetta
Paolo
P
Jenab
Mazda
M
Riboli
Elio
E
Kaaks
Rudolf
R
D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012007:Rectum / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I