Dissecting the association between breast cancer and scar conditions and fibrosis of skin : a bidirectional Mendelian randomization study

Abstract

Background Scar hyperplasia and skin fibrosis following breast cancer operation has long been recognized as one of the major effects affecting patients' quality of life. However, there is currently a lack of direct evidence examining the impact of breast cancer on scar conditions and fibrosis of skin. Methods In this study, a two-way, two-sample Mendelian randomisation (MR) approach utilising pooled data from a genome-wide association study (GWAS) we employed to investigate the potential causal relationship between breast cancer (BC) and scar conditions and fibrosis of skin.In forward MR, it was postulated that BC was the exposure factor, whereas in reverse MR, scar conditions and fibrosis of skin were posited as the exposure factors. To enhance the reliability of the results, two databases (finna-a-L12_SCARCONDITIONS; ukb-b-11403 ) were employed to examine these factors.In order to explore the potential relationship between BC and scar conditions and fibrosis of skin, various analytical techniques were utilised, including random effects inverse variance weighted (IVW) and MR-Egger analyses.Furthermore, sensitivity analyses and assessments of heterogeneity and multiplicity were conducted to enhance the reliability of the results. Results The MR analysis indicates that BC is associated with an elevated risk of scar conditions and fibrosis of skin(OR = 1.310, 95%CI = 1.052–1.630, p = 0.015 ) and(OR = 1.00047, 95%CI = 1.000016–1.000928, p = 0.042 ) .In contrast, the inverse MR analysis did not identify scar conditions and fibrosis of skin as a potential factor influencing BC risk.Furthermore, sensitivity analyses of these results demonstrated the absence of evidence for heterogeneity or pleiotropy. Conclusion This study showed that a positive causal relationship exists between BC and scar conditions and fibrosis of skin in European populations. This study also offers a novel perspective on the mechanism study of postoperative scar formation in breast cancer patients, and provides a novel basis for clinical assessment of patients' prognosis based on the status of surgical scarring in BC and the degree of dermal fibrosis.