Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.
Lukanova
Annekatrin
A
International Agency for Research on Cancer, Lyon, France.
Zeleniuch-Jacquotte
Anne
A
Lundin
Eva
E
Micheli
Andrea
A
Arslan
Alan A
AA
Rinaldi
Sabina
S
Muti
Paola
P
Lenner
Per
P
Koenig
Karen L
KL
Biessy
Carine
C
Krogh
Vittorio
V
Riboli
Elio
E
Shore
Roy E
RE
Stattin
Par
P
Berrino
Franco
F
Hallmans
Göran
G
Toniolo
Paolo
P
Kaaks
Rudolf
R
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
D014408:Biomarkers, Tumor; D002096:C-Peptide; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I