Henan University of Chinese Medicine, Zhengzhou, China.
The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Cancer Causes Control. 2024 Jan;35(1):55-62. doi: 10.1007/s10552-023-01766-z. Epub 2023 Aug 4.
The use of antidepressants has increased over the years, but the relationship between antidepressant use and the risk of breast cancer is not uniform because of confounding factors. We aimed to assess the effect of antidepressants on breast cancer risk using a two-sample Mendelian randomization (MR) approach.stet METHODS: Secondary data analysis was performed on pooled data from genome-wide association studies based on single-nucleotide polymorphisms that were highly correlated with antidepressants, SSRI drugs, and serotonin and prolactin levels were selected as instrumental variables to evaluate the association between antidepressants and SSRI drugs and prolactin levels with breast cancer and ER+/ER- breast cancer. We then performed a test of the hypothesis that SSRI drugs elevate prolactin concentrations. We performed two-sample Mendelian randomization analyses using inverse variance weighting, MR-Egger regression, and weighted median methods, respectively.
There was no significant risk association between antidepressant and SSRI use and the development of breast cancer, ER-positive or ER-negative breast cancer (P > 0.05), and serotonin concentration was not associated with breast cancer risk (P > 0.05). There was a positive causal relationship between prolactin levels and breast cancer (IVW, P = 0.02, OR = 1.058) and ER-positive breast cancer (Weighted median, P = 0.043, OR = 1.141; IVW, P = 0.009, OR = 1.125). Results in SSRI medication and prolactin levels showed no association between SSRI analogs and prolactin levels (P > 0.05).
Large MR analysis showed that antidepressants as well as SSRI drugs were not associated with breast cancer risk and the SSRI-prolactin-breast cancer hypothesis did not hold in our analysis.
近年来，抗抑郁药的使用有所增加，但由于混杂因素，抗抑郁药使用与乳腺癌风险之间的关系并不一致。我们旨在使用两样本孟德尔随机化（MR）方法评估抗抑郁药对乳腺癌风险的影响。
对基于单核苷酸多态性的全基因组关联研究的汇总数据进行二次数据分析，选择与抗抑郁药、SSRIs 药物和血清素及催乳素水平高度相关的单核苷酸多态性作为工具变量，评估抗抑郁药与 SSRIs 药物和催乳素水平与乳腺癌和 ER+/ER-乳腺癌的关系。然后，我们进行了一项假设检验，即 SSRIs 药物会升高催乳素浓度。我们分别使用逆方差加权、MR-Egger 回归和加权中位数方法进行两样本孟德尔随机化分析。
抗抑郁药和 SSRIs 药物的使用与乳腺癌、ER 阳性或 ER 阴性乳腺癌的发生没有显著的风险关联（P>0.05），血清素浓度与乳腺癌风险无关（P>0.05）。催乳素水平与乳腺癌（IVW，P=0.02，OR=1.058）和 ER 阳性乳腺癌（加权中位数，P=0.043，OR=1.141；IVW，P=0.009，OR=1.125）之间存在正的因果关系。SSRIs 药物和催乳素水平的结果显示，SSRIs 类似物与催乳素水平之间没有关联（P>0.05）。
大规模 MR 分析表明，抗抑郁药和 SSRIs 药物与乳腺癌风险无关，并且我们的分析中 SSRIs-催乳素-乳腺癌假说不成立。
