IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC).
Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.
Rinaldi
S
S
International Agency for Research on Cancer (IARC-WHO), 150 Cours Albert Thomas, 69372 Lyon, Cédex 08, France.
Peeters
P H M
PH
Berrino
F
F
Dossus
L
L
Biessy
C
C
Olsen
A
A
Tjonneland
A
A
Overvad
K
K
Clavel-Chapelon
F
F
Boutron-Ruault
M C
MC
Téhard
B
B
Nagel
G
G
Linseisen
J
J
Boeing
H
H
Lahmann
P H
PH
Trichopoulou
A
A
Trichopoulos
D
D
Koliva
M
M
Palli
D
D
Panico
S
S
Tumino
R
R
Sacerdote
C
C
van Gils
C H
CH
van Noord
P
P
Grobbee
D E
DE
Bueno-de-Mesquita
H B
HB
Gonzalez
C A
CA
Agudo
A
A
Chirlaque
M D
MD
Barricarte
A
A
Larrañaga
N
N
Quiros
J R
JR
Bingham
S
S
Khaw
K T
KT
Key
T
T
Allen
N E
NE
Lukanova
A
A
Slimani
N
N
Saracci
R
R
Riboli
E
E
Kaaks
R
R
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology*; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008875:Middle Aged; D009747:Nutritional Physiological Phenomena; D012307:Risk Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I