CRP, IL-1α, IL-1β, and IL-6 Levels and the Risk of Breast Cancer: A Two-Sample Mendelian Randomization Study

Background: Epidemiological studies have reported a positive association between inflammation and cancer risk. However, the association between inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of inflammation in BC risk. Methods We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1α, IL-1β, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies (GWAS) and the Breast Cancer Association Consortium (BCAC)). Next, we conducted the two-sample Mendelian randomization (MR) study for investigating the relationship of the abovementioned inflammatory factors with the incidence of BC. Results Genetically predicted CRP levels did not increase BC incidence (odds ratio (OR) 1.06, 95% confidence interval (CI) 0.98–1.12, P = 0.2059). IL-6 was not related to BC incidence (OR 1.05, 95% CI 0.95–1.16, P = 0.3297). It showed no association between genetically predicted IL-1α levels and BC incidence (OR 1.01, 95% CI 0.99–1.03, P = 0.2167). IL-1β levels were not related to overall BC incidence (OR 1.07, 95% CI 0.98–1.17, P = 0.1140); however, in subgroup analysis, genetically predicted IL-1β levels increased ER + BC incidence (OR 1.15, 95% CI 1.03–1.27, P = 0.0088), but no correlation was found with ER-BC (OR 1.00, 95% CI 0.86–1.18, P = 0.9510). Conclusions Our study suggested that CRP, IL-1α, and IL-6 levels were not related to BC incidence; however, genetically predicted IL-1β levels were found to increase ER + BC susceptibility.