The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study

Frontiers in Genetics

Genetics

Yuxiang Lin¹  Fangmeng Fu¹  Xingxing Yu²  Mengjie Song²  Yanyu Zhang²  Pingxiu Zhu²  Haomin Yang²  Shuqing Zou² 

[1] Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China;Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China;Breast Cancer Institute, Fujian Medical University, Fuzhou, China;Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China;

关键词: breast cancer;    chemokine;    mendelian randomization;    molecular subtypes of breast cancer;    survival;   

DOI  :  10.3389/fgene.2022.1004931

 received in 2022-07-27, accepted in 2022-12-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Despite the potential role of several chemokines in the migration of cytotoxic immune cells to prohibit breast cancer cell proliferation, a comprehensive view of chemokines and the risk and prognosis of breast cancer is scarce, and little is known about their causal associations.Methods: With a two-sample Mendelian randomization (MR) approach, genetic instruments associated with 30 plasma chemokines were created. Their genetic associations with breast cancer and its survival by molecular subtypes were extracted from the recent genome-wide association study of 133,384 breast cancer cases and 113,789 controls, with available survival information for 96,661 patients. We further tested the associations between the polygenic risk score (PRS) for chemokines and breast cancer in the UK Biobank cohort using logistic regression models, while the association with breast cancer survival was tested using Cox regression models. In addition, the association between chemokine expression in tumors and breast cancer survival was also analyzed in the TCGA cohort using Cox regression models.Results: Plasma CCL5 was causally associated with breast cancer in the MR analysis, which was significant in the luminal and HER-2 enriched subtypes and further confirmed using PRS analysis (OR = 0.94, 95% CI = 0.89–1.00). A potential causal association with breast cancer survival was only found for plasma CCL19, especially for ER-positive patients. Although not replicated in the UK Biobank, we still found an inverse association between CCL19 expression in tumors and breast cancer overall and relapse-free survival in the TCGA cohort (HR = 0.58, 95% CI = 0.35–0.95).Conclusion: We observed an inverse association between genetic predisposition to CCL5 and breast cancer, while CCL19 was associated with breast cancer survival. These associations suggested the potential of these chemokines as tools for breast cancer prevention and treatment.

【 授权许可】

Unknown   
Copyright © 2023 Yu, Zhang, Lin, Zou, Zhu, Song, Fu and Yang.