Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer
Abstract This study uses Mendelian randomization (MR) to investigate the causal roles of CD40 and CD40L in BC.Data from genome-wide association studies (GWAS) on BC (overall, ER-positive, and ER-negative subtypes) and CD40/CD40L levels were obtained from the IEU database. Causal associations were as...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-99410-0 |
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| author | Junyu Yi Qingfeng Chen Xiaoyi Liu Yan Mao Yongmei Wang Meng Lv Haibo Wang Yuanyuan Wang |
| author_facet | Junyu Yi Qingfeng Chen Xiaoyi Liu Yan Mao Yongmei Wang Meng Lv Haibo Wang Yuanyuan Wang |
| author_sort | Junyu Yi |
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| description | Abstract This study uses Mendelian randomization (MR) to investigate the causal roles of CD40 and CD40L in BC.Data from genome-wide association studies (GWAS) on BC (overall, ER-positive, and ER-negative subtypes) and CD40/CD40L levels were obtained from the IEU database. Causal associations were assessed using the inverse-variance weighted (IVW) method, with additional robustness checks performed via MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran’s Q test and MR-PRESSO, were conducted to assess heterogeneity and pleiotropy. Reverse MR analyses were also performed to examine if BC influences CD40/CD40L levels.A borderline significant association was found between CD40 levels and overall BC risk (IVW OR 1.027, 95% CI 1.000–1.054, p = 0.049), with a more robust association observed for ER-positive BC (OR 1.048, 95% CI 1.016–1.082, p = 0.003). No significant associations were found between CD40 levels and ER-negative BC. CD40L did not show any significant associations with BC. Reverse MR analysis indicated no causal effect of BC on CD40/CD40L levels. CD40 is causally associated with a borderline increase in overall BC risk and a more significant increase in ER-positive BC risk. These findings suggest a potential role for CD40 in BC, particularly in ER-positive cases. |
| format | Article |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-35b125d5aa3840d9aa7dbbf6b1444c872025-08-20T01:47:32ZengNature PortfolioScientific Reports2045-23222025-04-011511910.1038/s41598-025-99410-0Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancerJunyu Yi0Qingfeng Chen1Xiaoyi Liu2Yan Mao3Yongmei Wang4Meng Lv5Haibo Wang6Yuanyuan Wang7Breast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityBreast Disease Center, The Affiliated Hospital of Qingdao UniversityAbstract This study uses Mendelian randomization (MR) to investigate the causal roles of CD40 and CD40L in BC.Data from genome-wide association studies (GWAS) on BC (overall, ER-positive, and ER-negative subtypes) and CD40/CD40L levels were obtained from the IEU database. Causal associations were assessed using the inverse-variance weighted (IVW) method, with additional robustness checks performed via MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran’s Q test and MR-PRESSO, were conducted to assess heterogeneity and pleiotropy. Reverse MR analyses were also performed to examine if BC influences CD40/CD40L levels.A borderline significant association was found between CD40 levels and overall BC risk (IVW OR 1.027, 95% CI 1.000–1.054, p = 0.049), with a more robust association observed for ER-positive BC (OR 1.048, 95% CI 1.016–1.082, p = 0.003). No significant associations were found between CD40 levels and ER-negative BC. CD40L did not show any significant associations with BC. Reverse MR analysis indicated no causal effect of BC on CD40/CD40L levels. CD40 is causally associated with a borderline increase in overall BC risk and a more significant increase in ER-positive BC risk. These findings suggest a potential role for CD40 in BC, particularly in ER-positive cases.https://doi.org/10.1038/s41598-025-99410-0Mendelian randomization CD40CD40LBreast cancerER-positiveCausal association |
| spellingShingle | Junyu Yi Qingfeng Chen Xiaoyi Liu Yan Mao Yongmei Wang Meng Lv Haibo Wang Yuanyuan Wang Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer Scientific Reports Mendelian randomization CD40 CD40L Breast cancer ER-positive Causal association |
| title | Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer |
| title_full | Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer |
| title_fullStr | Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer |
| title_full_unstemmed | Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer |
| title_short | Genetic evidence from Mendelian randomization links CD40 levels to increased risk of estrogen receptor-positive breast cancer |
| title_sort | genetic evidence from mendelian randomization links cd40 levels to increased risk of estrogen receptor positive breast cancer |
| topic | Mendelian randomization CD40 CD40L Breast cancer ER-positive Causal association |
| url | https://doi.org/10.1038/s41598-025-99410-0 |
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