Abstract
Breast cancer (BC) is the leading cause of cancer death in women. Adipokines, and other inflammation molecules linked to adiposity, are suspected to be involved in breast carcinogenesis, however prospective findings are inconclusive. In a prospective nested case-control study within the EPIC-Varese cohort, we used conditional logistic regression to estimate rate ratios (RRs) for BC, with 95% confidence intervals (CI), in relation to plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6, leptin, and adiponectin, controlling for BC risk factors. After a median 14.9 years, 351 BC cases were identified and matched to 351 controls. No marker was significantly associated with BC risk overall. Significant interactions between menopausal status and CRP, leptin, and adiponectin were found. Among postmenopausal women, high CRP was significantly associated with increased BC risk, and high adiponectin with significantly reduced risk. Among premenopausal women, high TNF-α was associated with significantly increased risk, and high leptin with reduced risk; interleukin-6 was associated with increased risk only in a continuous model. These findings constitute further evidence that inflammation plays a role in breast cancer. Interventions to lower CRP, TNF-α, and interleukin-6 and increase adiponectin levels may contribute to preventing BC.
Highlights
Breast cancer is the commonest cancer and leading cause of cancer death in women worldwide, with an estimated 1.7 million cases and over 520,000 deaths in 2012, accounting for 25% of all female cancers and 15% of all female cancer deaths[1]
We carried out a case-control study to prospectively assess whether pre-diagnostic levels of C-reactive protein (CRP), TNF-α, IL-6, leptin, and adiponectin in plasma are associated with risk of developing breast cancer
None of the other biomarkers was significantly associated with breast cancer risk premenopausal women. In this nested case-control study, none of the inflammatory biomarkers analyzed was associated with breast cancer risk in the overall population
Summary
Breast cancer is the commonest cancer and leading cause of cancer death in women worldwide, with an estimated 1.7 million cases and over 520,000 deaths in 2012, accounting for 25% of all female cancers and 15% of all female cancer deaths[1]. C-reactive protein (CRP), an acute-phase protein of hepatic origin that is a sensitive yet nonspecific marker of the inflammatory response, has been associated with breast cancer risk in some[4,5,6,7] but not all studies[6]. Altered levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), adiponectin, and leptin have important roles in promoting inflammation in obesity and chronic inflammatory diseases[9], and may play a role in carcinogenesis[8,10]. Prospective studies on markers of inflammation and breast cancer risk have produced conflicting results[11,12,13]. We carried out a case-control study to prospectively assess whether pre-diagnostic levels of CRP, TNF-α, IL-6, leptin, and adiponectin in plasma are associated with risk of developing breast cancer
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