The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study
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:...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1004931/full |
| _version_ | 1797962249195749376 |
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| author | Xingxing Yu Yanyu Zhang Yuxiang Lin Yuxiang Lin Yuxiang Lin Shuqing Zou Pingxiu Zhu Mengjie Song Fangmeng Fu Fangmeng Fu Fangmeng Fu Haomin Yang |
| author_facet | Xingxing Yu Yanyu Zhang Yuxiang Lin Yuxiang Lin Yuxiang Lin Shuqing Zou Pingxiu Zhu Mengjie Song Fangmeng Fu Fangmeng Fu Fangmeng Fu Haomin Yang |
| author_sort | Xingxing Yu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T01:10:24Z |
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| id | doaj.art-03dd7f97cb5a4e2aa21a7ec15f80f690 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T01:10:24Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-03dd7f97cb5a4e2aa21a7ec15f80f6902023-01-04T06:35:23ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10049311004931The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization studyXingxing Yu0Yanyu Zhang1Yuxiang Lin2Yuxiang Lin3Yuxiang Lin4Shuqing Zou5Pingxiu Zhu6Mengjie Song7Fangmeng Fu8Fangmeng Fu9Fangmeng Fu10Haomin Yang11Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, ChinaDepartment of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of General Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaBreast Cancer Institute, Fujian Medical University, Fuzhou, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, ChinaDepartment of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of General Surgery, Fujian Medical University Union Hospital, Fuzhou, ChinaBreast Cancer Institute, Fujian Medical University, Fuzhou, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.1004931/fullbreast cancerchemokinemendelian randomizationmolecular subtypes of breast cancersurvival |
| spellingShingle | Xingxing Yu Yanyu Zhang Yuxiang Lin Yuxiang Lin Yuxiang Lin Shuqing Zou Pingxiu Zhu Mengjie Song Fangmeng Fu Fangmeng Fu Fangmeng Fu Haomin Yang The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study Frontiers in Genetics breast cancer chemokine mendelian randomization molecular subtypes of breast cancer survival |
| title | The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study |
| title_full | The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study |
| title_fullStr | The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study |
| title_full_unstemmed | The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study |
| title_short | The association between plasma chemokines and breast cancer risk and prognosis: A mendelian randomization study |
| title_sort | association between plasma chemokines and breast cancer risk and prognosis a mendelian randomization study |
| topic | breast cancer chemokine mendelian randomization molecular subtypes of breast cancer survival |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1004931/full |
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