Oncology Department, China Academy of Chinese Medical Sciences Guang'anmen Hospital, Beijing, China.
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
PLoS One. 2023 Sep 1;18(9):e0291006. doi: 10.1371/journal.pone.0291006. eCollection 2023.
Based on epidemiological reports, severe mental illness (SMI) and breast cancer (BC) risk are linked positively. However, it is susceptible to clinical confounding factors, such as smoking, alcohol consumption, etc. Here, we performed a two-sample, two-step multivariable Mendelian randomization (MR) research to explore how the SMI etiologically influences BC risk and to quantify mediating effects of known modifiable risk factors.
Data concerning the single nucleotide polymorphism (SNP)-associated with schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), and BC were obtained from two large consortia: the Breast Cancer Association Consortium (BCAC) and the Psychiatric Genomics Consortium (PGC). Then, the correlations of the previous SMI with the BC prevalence and the potential impact of mediators were explored through the two-sample and two-step MR analyses.
In two-sample MR, schizophrenia increased BC incidence (odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02-1.10, P = 0.001). In subgroup analysis, schizophrenia increased ER+ BC (OR 1.06, 95% CI 1.03-1.10, P = 0.0009) and ER-BC (OR 1.06, 95% CI 1.01-1.11, P = 0.0123) incidences. Neither MDD nor BD elevated the BC risk. In two-step MR, smoking explained 11.29% of the schizophrenia-all BC risk association.
Our study indicates that schizophrenia increases susceptibility to breast cancer, with smoking playing a certain mediating role. Therefore, BC screening and smoking should be incorporated into the health management of individuals with schizophrenia.
基于流行病学报告，严重精神疾病（SMI）和乳腺癌（BC）风险呈正相关。然而，这容易受到临床混杂因素的影响，如吸烟、饮酒等。在这里，我们进行了两样本、两阶段多变量孟德尔随机化（MR）研究，以探讨 SMI 如何在病因学上影响 BC 风险，并量化已知可改变的风险因素的中介作用。
与精神分裂症、双相情感障碍（BD）、重度抑郁症（MDD）和 BC 相关的单核苷酸多态性（SNP）数据来自两个大型联盟：乳腺癌协会联盟（BCAC）和精神疾病基因组学联盟（PGC）。然后，通过两样本和两阶段 MR 分析，探讨了先前的 SMI 与 BC 患病率的相关性以及中介物的潜在影响。
在两样本 MR 中，精神分裂症增加了 BC 的发病率（比值比（OR）1.06，95%置信区间（CI）1.02-1.10，P=0.001）。在亚组分析中，精神分裂症增加了 ER+BC（OR 1.06，95% CI 1.03-1.10，P=0.0009）和 ER-BC（OR 1.06，95% CI 1.01-1.11，P=0.0123）的发病率。MDD 或 BD 均未增加 BC 风险。在两阶段 MR 中，吸烟解释了精神分裂症与所有 BC 风险关联的 11.29%。
我们的研究表明，精神分裂症增加了患乳腺癌的易感性，吸烟起着一定的中介作用。因此，BC 筛查和吸烟应纳入精神分裂症患者的健康管理中。
