Abstract
To determine whether genetically predicted circulating levels of cytokines are associated with risk of overall breast cancer (BC), estrogen receptor (ER)-positive and ER-negative BC, we conducted two-sample MR analyses using data from the most comprehensive genome-wide association studies (GWAS) on cytokines in 8293 Finnish participants and the largest BC GWAS from the Breast Cancer Association Consortium (BCAC) with totally 122,977 BC cases and 105,974 healthy controls. We systematically screened 41 cytokines (of which 24 cytokines have available instruments) and identified that genetically predicted circulating levels (1-SD increase) of MCP1 (OR: 1.08; 95% CIs: 1.03–1.12; P value: 3.55 × 10−4), MIP1b (OR: 1.02; 95% CIs: 1.01–1.04; P value: 2.70 × 10−3) and IL13 (OR: 1.06; 95% CIs: 1.03–1.10; P value: 3.33 × 10−4) were significantly associated with increased risk of overall BC, as well as ER-positive BC. In addition, higher levels of MIP1b and IL13 were also significantly associated with increased risk of ER-negative BC. These findings suggest the crucial role of cytokines in BC carcinogenesis and potential of targeting specific inflammatory cytokines for BC prevention.
Highlights
Breast cancer (BC) remains the main cause of cancer death and the second most common female cancer in western countries, the death rate of BC has dropped by 40% from 1989 to 20161,2
We evaluated whether genetically predicted circulating levels of cytokines are associated with risk of overall BC, estrogen receptor (ER)-positive and ER-negative BC
Higher levels of eight cytokines was associated with increased risk of BC, while higher level of migration inhibitory factor (MIF) was associated with decreased risk of BC
Summary
Breast cancer (BC) remains the main cause of cancer death and the second most common female cancer in western countries, the death rate of BC has dropped by 40% from 1989 to 20161,2. The role of cytokines in BC carcinogenesis has been widely explored by observational studies and yielded equivocal results, with suggestive associations between risk of BC and abnormal levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), C-reactive protein (CRP), transforming growth factor β (TGF-β)[10,11,12,13], etc. These relationships between inflammatory cytokines and BC risk identified in observational studies could be susceptible to confounding factors, limited follow-up time, small sample size and the reverse causation, which might mislead the conclusions[14]. The potential causality of individual cytokines in determining BC risk remains elusive
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
