title: Obesity-related markers and breast cancer in CPS-II Nutrition Cohort.
abstract: Low circulating levels of adiponectin and high levels of insulin-like growth factor-1 (IGF-1), C-reactive protein (CRP), and C-peptide have been shown to be related to postmenopausal breast cancer risk, and to partially mediate the obesity-postmenopausal breast cancer association; however, data from prospective studies, especially those limited to non-users of postmenopausal hormones, are sparse. To further evaluate these associations, we measured these markers in a case-control study nested in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort. Plasma samples from 302 postmenopausal breast cancer cases and matched controls were analyzed. None of the women were taking postmenopausal hormones at blood draw. Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Low levels of total adiponectin and high levels of total IGF-1 and CRP were associated with increased breast cancer risk, but associations were not statistically significant. The association with C-peptide was statistically significant (T3 vs. T1: OR=1.63, 95% CI 1.08-2.45; p-value for linear trend=0.001), but was slightly attenuated after further adjustment for BMI (T3 vs. T1: OR=1.51, 95% CI 0.99-2.31; p-value for linear trend=0.004). The association between BMI and breast cancer risk was attenuated toward the null after controlling for C-peptide (from OR=1.43 to OR=1.25 for BMI ≥30 kg/m(2) compared to <25 kg/m>(2)). The elevated risk of postmenopausal breast cancer associated with higher circulating levels of C-peptide is consistent with a role of hyperinsulinemia in breast carcinogenesis, and might account for some of the higher risk associated with obesity.
authors.affiliation: Epidemiology Research Program, American Cancer Society Atlanta, GA, USA.
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Alpa V
authors.initials: AV
authors.lastname: Patel
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Teras
authors.forename: Juzhong
authors.initials: J
authors.lastname: Sun
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Stevens
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
keywords: Breast cancer; C-peptide; obesity; risk
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