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Int J Mol Epidemiol Genet 2013;4(3):156-166

Original Article
Obesity-related markers and breast cancer in CPS-II Nutrition Cohort

Mia M Gaudet, Alpa V Patel, Lauren R Teras, Juzhong Sun, Peter T Campbell, Victoria L Stevens, Eric J Jacobs, Susan M
Gapstur

Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA

Received August 8, 2013; Accepted August 30, 2013; Epub September 12, 2013; Published September 15, 2013

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/m2
compared to <25 kg/m2). 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. (IJMEG1308002).

Keywords: Breast cancer, obesity, C-peptide, risk

Address correspondence to: Dr. Mia M Gaudet, Epidemiology Research Program, American Cancer Society, 250 Williams
Street, NW, Atlanta, GA, 30303, USA. Tel: 404-329-7762; Fax: 404-327-6450; E-mail: mia.gaudet@cancer.org