Peng Haoxin, Wu Xiangrong, Ge Fan, Huo Zhenyu, Wen Yaokai, Li Caichen, Lin Jinsheng, Liang Hengrui, Zhong Ran, Liu Jun, Wang Runchen, He Jianxing, Liang Wenhua
Department of Thoracic Oncology and Surgery, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Nanshan School, Guangzhou Medical University, Guangzhou, China.
Ann Transl Med. 2021 Mar;9(5):401. doi: 10.21037/atm-20-5372.
Epidemiologic findings suggested that bipolar disorder (BD) may be associated with an increased risk of breast cancer. However, there are few studies that comprehensively evaluating their correlation and the causal effect remains unknown. With a two-sample Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.
Utilizing 14 BD-related single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) identified by the latest genome-wide association studies (GWASs), we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122,977 cases and 105,974 controls. Study-specific estimates were summarized using inverse variance weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical types of breast cancer were also conducted.
MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR =1.059; 95% CI: 1.008-1.112, P=0.0229). When results were examined by immunohistochemical type, no causal effects between genetically predicted BD and estrogen receptor (ER)-positive breast cancer (OR =1.049, 95% CI: 0.999-1.102 P=0.0556) and ER-negative breast cancer (OR =1.032, 95% CI: 0.953-1.116 P=0.4407) were observed. Additionally, the results demonstrated the absence of the horizontal pleiotropy.
Our findings provided evidence for a causal relationship between genetically predicted BD and an increased risk of breast cancer overall. Further studies are warranted to investigate the underlying mechanism.
流行病学研究结果表明，双相情感障碍（BD）可能与乳腺癌风险增加有关。然而，很少有研究全面评估它们之间的相关性，因果关系仍不清楚。通过两样本孟德尔随机化（MR）方法，我们能够研究基因预测的BD与乳腺癌风险之间的因果关系。
利用最新全基因组关联研究（GWAS）确定的14个与BD相关的单核苷酸多态性（SNP）作为工具变量（IV），我们使用乳腺癌协会联盟的汇总统计数据，对122977例病例和105974例对照进行研究，调查基因预测的BD与乳腺癌风险之间的相关性。采用逆方差加权（IVW）方法汇总特定研究的估计值。为了进一步评估多效性，实施了加权中位数和MR-Egger回归方法。还根据不同免疫组化类型的乳腺癌进行了亚组分析。
MR分析表明，基因预测的BD与乳腺癌风险增加存在因果关系（OR =1.059；95%CI：1.008-1.112，P=0.0229）。按免疫组化类型检查结果时，未观察到基因预测的BD与雌激素受体（ER）阳性乳腺癌（OR =1.049，95%CI：0.999-1.102，P=0.0556）和ER阴性乳腺癌（OR =1.032，95%CI：0.953-1.116，P=0.4407）之间存在因果效应。此外，结果表明不存在水平多效性。
我们的研究结果为基因预测的BD与总体乳腺癌风险增加之间的因果关系提供了证据。有必要进一步研究其潜在机制。
