Circulating inflammatory biomarkers, adipokines and breast cancer risk—a case-control study nested within the EPIC cohort

Background: Infammation has been hypothesized to play a role in the development and progression of breast can‑ cer and might diferently impact breast cancer risk among pre and postmenopausal women. We performed a nested case-control study to examine whether pre-diagnostic circulating concentrations of adiponectin, leptin, c-reactive protein (CRP), tumour necrosis factor-α, interferon-γ and 6 interleukins were associated with breast cancer risk, overall and by menopausal status. Methods: Pre-diagnostic levels of infammatory biomarkers were measured in plasma from 1558 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We used conditional logistic regression to estimate the odds ratios (ORs) of breast cancer at blood collection, per one standard deviation increase in biomarker concentration. Results: Cases were diagnosed at a mean age of 61.4 years on average 8.6 years after blood collection. No statisti‑ cally signifcant association was observed between infammatory markers and breast cancer risk overall. In premeno‑ pausal women, borderline signifcant inverse associations were observed for leptin, leptin-to-adiponectin ratio and CRP [OR= 0.89 (0.77–1.03), OR= 0.88 (0.76–1.01) and OR= 0.87 (0.75–1.01), respectively] while positive associations were observed among postmenopausal women [OR= 1.16 (1.05–1.29), OR= 1.11 (1.01–1.23), OR= 1.10 (0.99–1.22), respectively]. Adjustment for BMI strengthened the estimates in premenopausal women [leptin: OR = 0.83 (0.68– 1.00), leptin-to-adiponectin ratio: OR = 0.80 (0.66–0.97), CRP: OR = 0.85 (0.72–1.00)] but attenuated the estimates in postmenopausal women [leptin: OR = 1.09 (0.96–1.24), leptin-to-adiponectin ratio: OR = 1.02 (0.89–1.16), CRP: OR = 1.04 (0.92–1.16)]. Conclusions: Associations between CRP, leptin and leptin-to-adiponectin ratio with breast cancer risk may represent the dual efect of obesity by menopausal status although this deserves further investigation