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.
Verheus
Martijn
M
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Peeters
Petra H M
PH
Rinaldi
Sabina
S
Dossus
Laure
L
Biessy
Carine
C
Olsen
Anja
A
Tjønneland
Anne
A
Overvad
Kim
K
Jeppesen
Majbritt
M
Clavel-Chapelon
Françoise
F
Téhard
Bertrand
B
Nagel
Gabriele
G
Linseisen
Jakob
J
Boeing
Heiner
H
Lahmann
Petra H
PH
Arvaniti
Athina
A
Psaltopoulou
Theodora
T
Trichopoulou
Antonia
A
Palli
Domenico
D
Tumino
Rosario
R
Panico
Salvatore
S
Sacerdote
Carlotta
C
Sieri
Sabina
S
van Gils
Carla H
CH
Bueno-de-Mesquita
Bas H
BH
González
Carlos A
CA
Ardanaz
Eva
E
Larranaga
Nera
N
Garcia
Carmen Martinez
CM
Navarro
Carmen
C
Quirós
J Ramón
JR
Key
Tim
T
Allen
Naomi
N
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Slimani
Nadia
N
Riboli
Elio
E
Kaaks
Rudolf
R
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