Linking Physical Activity to Breast Cancer via Inflammation, Part 2: The Effect of Inflammation on Breast Cancer Risk

This review synthesized and appraised the evidence for an effect of inflammation on breast cancer risk. Systematic searches identified prospective cohort and Mendelian random-ization studies relevant to this review. Meta-analysis of 13 biomarkers of inflammation were conducted to appraise the evidence for an effect breast cancer risk; we examined the dose-response of these associations. Risk of bias was evaluated using the ROBINS-E tool and the quality of evidence was appraised with Grading of Recommendations Assessment, Development, and Evaluation. Thirty-four observational stud-ies and three Mendelian randomization studies were included. Meta-analysis suggested that women with the highest levels of C-reactive protein (CRP) had a higher risk of developing breast cancer [risk ratio (RR) = 1.13; 95% confidence interval (CI), 1.01-1.26] compared with women with the lowest levels. Women with highest levels of adipokines, particularly adipo-nectin (RR = 0.76; 95% CI, 0.61-0.91) had a reduced breast cancer risk, although this finding was not supported by Men-delian randomization analysis. There was little evidence of an effect of cytokines, including TNF z and IL6, on breast cancer risk. The quality of evidence for each biomarker ranged from very low to moderate. Beyond CRP, the published data do not clearly support the role of inflammation in the development of breast cancer.