自身免疫性疾病与乳腺癌之间的因果关系：欧洲人群中的一项两样本孟德尔随机化研究
Causality between autoimmune diseases and breast cancer: a two-sample Mendelian randomization study in a European population.
作者信息
Zhang Hengheng, Shen Guoshuang, Yang Ping, Wu Meijie, Li Jinming, Li Zitao, Zhao Fuxing, Liang Hongxia, Da Mengting, Wang Ronghua, Zhang Chengrong, Zhao Jiuda, Zhao Yi
机构信息
Qinghai University, Xining, China.
The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China.
出版信息
Discov Oncol. 2024 Sep 1;15(1):396. doi: 10.1007/s12672-024-01269-6.
BACKGROUND
The incidence of autoimmune diseases and breast cancer is significantly higher in women compared to men. Previous observational studies have not conclusively determined the relationship between these two conditions. This study utilizes the Mendelian randomization approach to investigate the genetic association between autoimmune diseases and breast cancer.
METHOD
Two-sample Mendelian randomization was conducted on a European population using the GWAS database. The inverse variance-weighted method served as the primary analytical approach. The MR-PRESSO test was applied to detect horizontal pleiotropy. To ensure result robustness, the FDR correction method was used.
RESULT
The study revealed that Sjögren's syndrome lowers the overall risk of breast cancer (OR 0.96, 95% CI [0.93-0.99], p = 0.011). Idiopathic inflammatory myopathy shows a protective effect against overall breast cancer (OR 0.98, 95% CI [0.97-0.99], p = 0.035). An association was identified between rheumatoid arthritis and overall breast cancer (OR 0.98, 95% CI [0.96-1.00], p = 0.050). No causal link was found between systemic lupus erythematosus, systemic sclerosis, and overall breast cancer. The study also suggests that Sjögren's syndrome, rheumatoid arthritis, and idiopathic inflammatory myopathy might reduce the risk of developing HER + breast cancer. Specifically, Sjögren's syndrome (OR = 0.90, 95% CI [0.83-0.98], p = 0.02), rheumatoid arthritis (OR = 0.94, 95% CI [0.91-0.98], p = 0.006), and idiopathic inflammatory myopathy (OR = 0.96, 95% CI [0.93-0.99], p = 0.036). Additionally, systemic lupus erythematosus was found to lower the risk of HER- breast cancer (OR = 0.95, 95% CI [0.91-0.99], p = 0.046). The study did not establish a causal relationship between these five autoimmune diseases and ER + or ER- breast cancer.
CONCLUSION
This study found that autoimmune diseases may act as protective factors against breast cancer risk.
背景
与男性相比，自身免疫性疾病和乳腺癌在女性中的发病率显著更高。先前的观察性研究尚未最终确定这两种疾病之间的关系。本研究采用孟德尔随机化方法来探究自身免疫性疾病与乳腺癌之间的遗传关联。
方法
利用全基因组关联研究（GWAS）数据库对欧洲人群进行两样本孟德尔随机化分析。采用逆方差加权法作为主要分析方法。应用MR-PRESSO检验来检测水平多效性。为确保结果的稳健性，使用了错误发现率（FDR）校正方法。
结果
该研究表明，干燥综合征可降低乳腺癌的总体风险（比值比[OR]为0.96，95%置信区间[CI][0.93 - 0.99]，p = 0.011）。特发性炎性肌病对总体乳腺癌显示出保护作用（OR为0.98，95% CI[0.97 - 0.99]，p = 0.035）。类风湿性关节炎与总体乳腺癌之间存在关联（OR为0.98，95% CI[0.96 - 1.00]，p = 0.050）。未发现系统性红斑狼疮、系统性硬化症与总体乳腺癌之间存在因果关系。该研究还表明，干燥综合征、类风湿性关节炎和特发性炎性肌病可能会降低发生人表皮生长因子受体2（HER）阳性乳腺癌的风险。具体而言，干燥综合征（OR = 0.90，95% CI[0.83 - 0.98]，p = 0.02）、类风湿性关节炎（OR = 0.94，95% CI[0.91 - 0.98]，p = 0.006）以及特发性炎性肌病（OR = 0.96，95% CI[0.93 - 0.99]，p = 0.036）。此外，发现系统性红斑狼疮可降低HER阴性乳腺癌的风险（OR = 0.95，95% CI[0.91 - 0.99]，p = 0.046）。该研究未证实这五种自身免疫性疾病与雌激素受体（ER）阳性或ER阴性乳腺癌之间存在因果关系。
结论
本研究发现自身免疫性疾病可能是乳腺癌风险的保护因素。
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