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 ORs and 95% confidence intervals (CI) 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 before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [OR, 1.94 (1.37-2.75); P ≤ 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36-2.68); P = 0.005], and CRP [OR, 1.41 (1.01-1.96); P = 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. Cancer Prev Res; 6(3); 188-95. ©2013 AACR.
- SourceAvailable from: Christine M Friedenreich[Show abstract] [Hide abstract]
ABSTRACT: Strong and consistent evidence exists that physical activity reduces breast cancer risk by 10-25 %, and several proposed biologic mechanisms have now been investigated in randomized, controlled, exercise intervention trials. Leading hypothesized mechanisms relating to postmenopausal breast cancer include adiposity, endogenous sex hormones, insulin resistance, and chronic low-grade inflammation. In addition, other pathways are emerging as potentially important, including those involving oxidative stress and telomere length, global DNA hypomethylation, immune function, and vitamin D exposure. Recent exercise trials in overweight/obese postmenopausal women implicate weight loss as a mechanism whereby exercise induces favorable changes in circulating estradiol levels and other biomarkers as well. Still it is plausible that some exercise-induced biomarker changes do not require loss of body fat, whereas others depend on abdominal fat loss. We highlight the latest findings from randomized, controlled trials of healthy postmenopausal women, relating exercise to proposed biomarkers for postmenopausal breast cancer risk.03/2013; 3(1). DOI:10.1007/s13668-013-0069-8
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ABSTRACT: Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.08/2013; 3(3):34-42. DOI:10.5493/wjem.v3.i3.34
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ABSTRACT: C-reactive protein (CRP) is a marker of systemic inflammation that has been associated with the incidence and prognosis for a number of different cancers. Recent data suggest that CRP may be a prognostic factor for liver cancer and cirrhosis. However, few long-term studies are available. We prospectively examined associations between serum CRP and subsequent risk of liver cancer incidence or chronic liver disease mortality in a nested case-control study performed in the Linxian Nutrition Intervention Trials cohort. Baseline serum CRP was measured for 220 incident liver cancer cases, 276 participants who died of chronic liver disease, and 1,018 age-, sex-, and trial-matched controls. Unconditional logistical regression models were used to estimate ORs and 95% confidence intervals (CI). Compared with the lowest quartile, subjects in the fourth quartile of serum CRP had a higher risk of liver cancer incidence (OR, 1.63; 95% CI, 1.06-2.51), with a significant Ptrend across quartiles (P = 0.01). The association with liver cancer was only significant among men (Q4 vs. Q1; OR, 2.00; 1.10-3.62), but not among women (Q4 vs. Q1; OR, 1.15; 0.60-2.22). For chronic liver disease deaths, the corresponding risk estimate in men and women was 2.95 (1.90-4.57), with a monotonic trend (P < 0.001). Higher serum CRP concentrations at baseline were associated with subsequent incidence of liver cancer and death from chronic liver disease. Our findings suggest that levels of systemic inflammation may serve as a long-term marker of liver cancer and liver disease. Cancer Epidemiol Biomarkers Prev; 24(2); 1-7. ©2015 AACR. ©2015 American Association for Cancer Research.British Journal of Cancer 09/2013; 109(7). DOI:10.1038/bjc.2013.546 · 4.82 Impact Factor