Circulating C-Reactive Protein and Breast Cancer Risk—Systematic Literature Review and Meta-analysis of Prospective Cohort Studies

We conducted a systematic literature review to explore the association between circulating C-reactive protein (CRP), a low-grade inflammation biomarker, and breast cancer risk. Relevant prospective studies in women were identified in PubMed and Web of Science until February 2015. Random-effects dose-response meta-analysis was conducted, overall and in post-menopausal women. Twelve out of 15 studies identified were included in the meta-analysis on any breast cancers (3,522 cases, 69,610 women) and nine on post-menopausal breast cancer (2,516 cases, 36,847 women). For each doubling of CRP concentration, a 7% (95% CI: 2%-12%) and 6% (95% CI: 1%-11%) increased risk was observed (I2=47% and 32%; P heterogeneity =0.04 and 0.17), respectively. The association was linear over most of the range of CRP concentrations. Positive associations remained in the studies that examined the exclusion of early years of follow-up. Associations were attenuated in studies adjusted for lifestyle factors, which partly explained the significant heterogeneity between studies in the overall analysis. On average, the associations in studies adjusted or not adjusted for body mass index were similar. Low-grade inflammation may have a role in breast cancer development. Additional prospective studies are needed to better understand confounding and effect modification from lifestyle factors.