Association between inflammatory factors and breast cancer: a Mendelian randomization study
SONG Wenfu1,2, GUAN Xutao1,2, WANG Bing1, SUN Shiling1,2, LI Yingying1,2
1. Department of Hematological and Oncology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan 450000, China; 2. First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, Henan 450000, China
Abstract：Objective To examine the causal relationship between inflammatory factors and breast cancer using two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and treatment of breast cancer. Methods Data of 91 inflammatory cytokines (n=14 824) and 5 subtypes of breast cancer (n=247 173) were collected from genome-wide association studies (GWAS). Single nucleotide polymorphism (SNP) associated with 91 inflammatory factors were selected as instrumental variables. MR analyses were performed using the inverse-variance weighted (IVW) method with inflammatory factors as exposure factors and breast cancer as outcome variables. The risk of type I error and the effect of multiple testing were reduced using the FDR correction method. The stability and reliability of the results were verified using Steiger test of directionality, MR-Egger regression, MR-PRESSO test and leave-one out method. Results Twenty-three inflammatory factors, including β nerve growth factor, interleukin-5, cystatin D and C-X-C chemokine ligand 1 were statistically associated with breast cancer (all P<0.05). After FDR adjustment, only evaluated abundance of oncostatin-M was found to be statistically associated with an increased risk of Basal-like (triple-negative) breast cancer (OR=1.186, 95%CI: 1.081-1.302, P=0.001, q=0.029), and the other 22 inflammatory factors had a high risk of type I error (all q>0.1). The sensitivity analysis indicated that the results were robust. No instrumental variables were found to have a significant impact on the results, which could exclude the influence of heterogeneity, horizontal pleiotropy, and reverse causality on the outcome. Conclusion The increased abundance of oncostatin-M may increase the risk of Basal-like (triple-negative) breast cancer.
宋文富, 关徐涛, 王冰, 孙士玲, 李盈盈. 炎症因子与乳腺癌关系的孟德尔随机化研究[J]. 预防医学, 2024, 36(8): 714-717,722.
SONG Wenfu, GUAN Xutao, WANG Bing, SUN Shiling, LI Yingying. Association between inflammatory factors and breast cancer: a Mendelian randomization study. Preventive Medicine, 2024, 36(8): 714-717,722.
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