Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).
It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Martijn
M
Verheus
Petra H M
PH
Peeters
Sabina
S
Rinaldi
Laure
L
Dossus
Carine
C
Biessy
Anja
A
Olsen
Anne
A
Tjønneland
Kim
K
Overvad
Majbritt
M
Jeppesen
Françoise
F
Clavel-Chapelon
Bertrand
B
Téhard
Gabriele
G
Nagel
Jakob
J
Linseisen
Heiner
H
Boeing
Petra H
PH
Lahmann
Athina
A
Arvaniti
Theodora
T
Psaltopoulou
Antonia
A
Trichopoulou
Domenico
D
Palli
Rosario
R
Tumino
Salvatore
S
Panico
Carlotta
C
Sacerdote
Sabina
S
Sieri
Carla H
CH
van Gils
Bas H
BH
Bueno-de-Mesquita
Carlos A
CA
González
Eva
E
Ardanaz
Nera
N
Larranaga
Carmen Martinez
CM
Garcia
Carmen
C
Navarro
J Ramón
JR
Quirós
Tim
T
Key
Naomi
N
Allen
Sheila
S
Bingham
Kay-Tee
KT
Khaw
Nadia
N
Slimani
Elio
E
Riboli
Rudolf
R
Kaaks
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D012307:Risk Factors
D002096:C-Peptide