Prediagnostic Leptin, Adiponectin, C-Reactive Protein, and the Risk of Postmenopausal Breast Cancer

Abstract

Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case-control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting prior to blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin (OR Q4 vs. Q1=1.94 [1.37-2.75]; Ptrend = < 0.001), the leptin:adiponectin ratio (OR=1.91 [1.36-2.68]; Ptrend = 0.005), and CRP (OR=1.41 [1.01-1.96]; Ptrend = 0.014) were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted.

Serum Adiponectin but not Leptin at Diagnosis as a Predictor of Breast Cancer Survival

“…Although earlier prospective study (Stattin et al, 2004) failed to an association between leptin and breast cancer risk, recent several nested case-control studies (Cust et al, 2009;Harris et al, 2011;Gross et al, 2013;Ollberding et al, 2013) suggested that high level of leptin was associated with increased breast cancer risk. A casecontrol study nested within the Multiethnic cohort (MEC) found an increased risk of postmenopausal breast cancer among women with the highest prediagnostic levels of leptin among normal weight women (Ollberding et al, 2013).…”

“…A casecontrol study nested within the Multiethnic cohort (MEC) found an increased risk of postmenopausal breast cancer among women with the highest prediagnostic levels of leptin among normal weight women (Ollberding et al, 2013). A recent study examining the relationship of leptin in the circulation and in the breast tissue of healthy women (Llanos et al, 2012), reported correlation for leptin r=0.62(p=0.009) for normal women, r=0.36 (p=0.08) for overweight women, and r=0.03 (p=0.86) for obese women.…”

Inflammatory Marker Changes in Postmenopausal Women after a Year-long Exercise Intervention Comparing High Versus Moderate Volumes

“…Intra-abdominal adiposity generally increases in women post-menopause and can contribute to increased levels of adipocytokines, such as CRP, IL6, and TNFa (2,3). Indeed, several recent case-control studies have demonstrated an association between breast cancer risk and increased levels of inflammatory cytokines (4,5), predominantly in obese, postmenopausal women (6,7), although these associations have not been consistently observed (8,9). Of these three proinflammatory cytokines, CRP is the most studied as a risk factor for breast cancer in prospective studies.…”

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer

“…Thus, exercise-induced changes in body fat which impart a less than 1% increase in plasma adiponectin levels for healthy, premenopausal women have an unknown effect for long-term protection against breast cancer in this at risk cohort. Another adipokine that is linked epidemiologically with breast cancer risk (30), and also mechanistically to carcinogenesis (31), is leptin. This protein is produced by adipocytes, fibroblasts, and also breast cancer cells once malignancy is present.…”