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| 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
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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 |
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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.
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Received: 25 March 2024
Revised: 27 June 2024
Published: 22 August 2024
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