Yin Yulai, Zhang Xiaoyu
Cangzhou Central Hospital, Hebei Medical University, Cangzhou, China.
Department of Thyroid and Breast Surgery Ⅲ, Cangzhou Central Hospital, Cangzhou, China.
Front Genet. 2024 Jul 23;15:1392341. doi: 10.3389/fgene.2024.1392341. eCollection 2024.
This Mendelian Randomization (MR) study aims to explore the potential bidirectional causal relationship between Inflammatory Bowel Disease (IBD) and Breast Cancer (BC). We utilized genetic instruments from the summary statistics of genome-wide association studies (GWAS) on IBD among individuals of European ancestry (12,882 cases and 21,770 controls) to investigate the association with breast cancer (14,910 cases and 17,588 controls) and . The primary causal estimates were obtained using the Inverse Variance Weighting Method (IVW), and the robustness of the results was evaluated through a series of sensitivity analyses. The study found a positive impact of genetically predicted IBD on breast cancer (OR = 1.047; 95% CI:1.009-1.087; = 0.014); in the analysis of IBD subtypes, genetically predicted Crohn's Disease (CD) also had a positive effect on breast cancer (OR = 1.044; 95% CI:1.015-1.073; = 0.002), but genetically predicted Ulcerative Colitis (UC) did not show a significant effect on breast cancer ( > 0.05). The reverse Mendelian Randomization analysis indicated that genetically predicted breast cancer promoted the overall occurrence of IBD (OR = 1.112; 95% CI:1.022-1.211; = 0.014); however, genetically predicted breast cancer did not show a significant correlation with IBD subtypes (CD and UC) ( > 0.05). Genetic predictions indicate a positive effect of Crohn's Disease (CD) on the risk of Estrogen Receptor-Positive Breast Cancer (ER + BC), with (OR = 1.021; 95% CI:1.002-1.040; = 0.002). Furthermore, a reverse Mendelian randomization analysis reveals that genetically predicted ER + BC contributes to the increased incidence of ulcerative colitis (UC), as indicated by (OR = 1.098; 95% CI:1.032-1.168; = 0.003). In contrast, genetically predicted Estrogen Receptor-Negative Breast Cancer (ER-BC) has been shown to promote the overall occurrence of inflammatory bowel disease (IBD), with (OR = 1.153; 95% CI:1.008-1.319; = 0.037). However, bidirectional two-sample Mendelian randomization analyses between other pairs did not reveal any significant associations ( > 0.05). This study elucidates the bidirectional causal association between breast cancer and inflammatory bowel disease, highlighting the necessity of screening for IBD in breast cancer patients and for breast cancer in IBD patients in clinical settings.
这项孟德尔随机化（MR）研究旨在探讨炎症性肠病（IBD）与乳腺癌（BC）之间潜在的双向因果关系。我们利用欧洲血统个体中炎症性肠病全基因组关联研究（GWAS）汇总统计数据中的遗传工具（12882例病例和21770例对照）来研究与乳腺癌（14910例病例和17588例对照）的关联。主要因果估计采用逆方差加权法（IVW）获得，并通过一系列敏感性分析评估结果的稳健性。研究发现，遗传预测的IBD对乳腺癌有正向影响（OR = 1.047；95%CI：1.009 - 1.087；P = 0.014）；在IBD亚型分析中，遗传预测的克罗恩病（CD）对乳腺癌也有正向影响（OR = 1.044；95%CI：1.015 - 1.073；P = 0.002），但遗传预测的溃疡性结肠炎（UC）对乳腺癌未显示出显著影响（P>0.05）。反向孟德尔随机化分析表明，遗传预测的乳腺癌促进了IBD的总体发生（OR = 1.112；95%CI：1.022 - 1.211；P = 0.014）；然而，遗传预测的乳腺癌与IBD亚型（CD和UC）未显示出显著相关性（P>0.05）。遗传预测表明克罗恩病（CD）对雌激素受体阳性乳腺癌（ER + BC）风险有正向影响，（OR = 1.021；95%CI：1.002 - 1.040；P = 0.002）。此外，反向孟德尔随机化分析显示，遗传预测的ER + BC导致溃疡性结肠炎（UC）发病率增加，（OR = 1.098；95%CI：1.032 - 1.168；P = 0.003）。相比之下，遗传预测的雌激素受体阴性乳腺癌（ER - BC）已被证明可促进炎症性肠病（IBD）的总体发生，（OR = 1.153；95%CI：1.008 - 1.319；P = 0.037）。然而，其他配对之间的双向双样本孟德尔随机化分析未发现任何显著关联（P>0.05）。本研究阐明了乳腺癌与炎症性肠病之间的双向因果关联，强调了在临床环境中对乳腺癌患者进行IBD筛查以及对IBD患者进行乳腺癌筛查的必要性。
