Ren Fei, Shang Qingyao, Zhao Shuangtao, Yang Chenxuan, Feng Kexin, Liu Jiaxiang, Kang Xiyu, Zhang Ruixuan, Wang Xiang, Wang Xin
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Thoracic Surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China.
Front Psychiatry. 2023 Jun 28;14:1179562. doi: 10.3389/fpsyt.2023.1179562. eCollection 2023.
Previous observational studies have showed that certain psychiatric disorders may be linked to breast cancer risk, there is, however, little understanding of relationships between mental disorders and a variety of breast diseases. This study aims to investigate if mental disorders influence the risks of overall breast cancer, the two subtypes of breast cancer (ER+ and ER-), breast benign tumors and breast inflammatory diseases.
During our research, genome-wide association study (GWAS) data for seven psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, panic disorder, obsessive-compulsive disorder and anorexia nervosa) from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were selected, and single-nucleotide polymorphisms (SNPs) significantly linked to these mental disorders were identified as instrumental variables. GWAS data for breast diseases came from the Breast Cancer Association Consortium (BCAC) as well as the FinnGen consortium. We performed two-sample Mendelian randomization (MR) analyses and multivariable MR analyses to assess these SNPs' effects on various breast diseases. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses.
When the GWAS data of psychiatric disorders were derived from the PGC, our research found that schizophrenia significantly increased the risks of overall breast cancer (two-sample MR: OR 1.05, 95%CI [1.03-1.07], = 3.84 × 10; multivariable MR: OR 1.06, 95%CI [1.04-1.09], = 2.34 × 10), ER+ (OR 1.05, 95%CI [1.02-1.07], = 5.94 × 10) and ER- (two-sample MR: OR 1.04, 95%CI [1.01-1.07], = 0.006; multivariable MR: OR 1.06, 95%CI [1.02-1.10], = 0.001) breast cancer. Nevertheless, major depressive disorder only showed significant positive association with overall breast cancer (OR 1.12, 95%CI [1.04-1.20], = 0.003) according to the two-sample MR analysis, but not in the multivariable MR analysis. In regards to the remainder of the mental illnesses and breast diseases, there were no significant correlations. While as for the data from the UK Biobank, schizophrenia did not significantly increase the risk of breast cancer.
The correlation between schizophrenia and breast cancer found in this study may be false positive results caused by underlying horizontal pleiotropy, rather than a true cause-and-effect relationship. More prospective studies are still needed to be carried out to determine the definitive links between mental illnesses and breast diseases.
以往的观察性研究表明，某些精神疾病可能与乳腺癌风险有关，然而，对于精神障碍与多种乳腺疾病之间的关系了解甚少。本研究旨在调查精神障碍是否会影响总体乳腺癌、两种乳腺癌亚型（雌激素受体阳性[ER+]和雌激素受体阴性[ER-]）、乳腺良性肿瘤和乳腺炎性疾病的风险。
在我们的研究中，选择了来自精神基因组学联盟（PGC）和英国生物银行的七种精神疾病（精神分裂症、重度抑郁症、双相情感障碍、创伤后应激障碍、惊恐障碍、强迫症和神经性厌食症）的全基因组关联研究（GWAS）数据，并将与这些精神障碍显著相关的单核苷酸多态性（SNP）鉴定为工具变量。乳腺疾病的GWAS数据来自乳腺癌协会联盟（BCAC）以及芬兰基因联盟。我们进行了两样本孟德尔随机化（MR）分析和多变量MR分析，以评估这些SNP对各种乳腺疾病的影响。通过敏感性分析评估异质性和多效性。
当精神疾病的GWAS数据来自PGC时，我们的研究发现，精神分裂症显著增加了总体乳腺癌（两样本MR：比值比[OR]1.05，95%置信区间[CI][1.03 - 1.07]，P = 3.84×10；多变量MR：OR 1.06，95%CI[1.04 - 1.09]，P = 2.34×10）、ER+（OR 1.05，95%CI[1.02 - 1.07]，P = 5.94×10）和ER-（两样本MR：OR 1.04，95%CI[1.01 - 1.07]，P = 0.006；多变量MR：OR 1.06，95%CI[1.02 - 1.10]，P = 0.001）乳腺癌的风险。然而，根据两样本MR分析，重度抑郁症仅与总体乳腺癌呈显著正相关（OR 1.12，95%CI[1.04 - 1.20]，P = 0.003），但在多变量MR分析中并非如此。对于其余的精神疾病和乳腺疾病，没有显著相关性。至于来自英国生物银行的数据，精神分裂症并未显著增加乳腺癌风险。
本研究中发现的精神分裂症与乳腺癌之间的相关性可能是由潜在的水平多效性导致的假阳性结果，而非真正的因果关系。仍需要进行更多的前瞻性研究来确定精神疾病与乳腺疾病之间的确切联系。
