Jia Lijun, Lv Wei, Liang Liang, Ma Yuguang, Ma Xingcong, Zhang Shuqun, Zhao Yonglin
Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an 710004, China.
J Clin Med. 2023 Jan 1;12(1):347. doi: 10.3390/jcm12010347.
Several studies have shown that female reproductive factors are associated with breast cancer (BC), but the results differ. We conducted two-sample MR in the present work. The raw data applied in the MR study were all from the Genome-wide association study (GWAS) database. The causal effect of reproductive factors on breast cancer were mainly estimated by the standard inverse variance weighted (IVW) method. Cochran's Q test and I statistics were used to assess heterogeneity. The pleiotropy was evaluated by MR-Egger intercept test and MR-PRESSO. Finally, the leave-one-out analysis was performed to evaluate the robustness of the MR results. We found that there was a negative causal effect of the age at last live birth on BC (OR = 0.687, 95%CI = 0.539-0.875, = 0.002) and positive effect of the age at menopause on BC (OR = 1.054, 95%CI = 1.034-1.075, = 8.010 × 10). Additionally, there were null effects of the age at menarche (OR = 0.977, 95%CI = 0.915-1.043, = 0.484), the age at first sexual intercourse (OR = 1.053, 95%CI = 0.958-1.157, = 0.284) and the age at first birth (OR = 0.981, 95%CI = 0.936-1.027, = 0.404) on BC. All these results were reliable and stable. In conclusion, the present study showed that younger age at last birth and older age at menopause could increase the risk of BC.
多项研究表明，女性生殖因素与乳腺癌（BC）相关，但结果存在差异。在本研究中，我们进行了两样本孟德尔随机化分析。孟德尔随机化研究中使用的原始数据均来自全基因组关联研究（GWAS）数据库。生殖因素对乳腺癌的因果效应主要通过标准逆方差加权（IVW）方法进行估计。采用 Cochran's Q 检验和 I 统计量评估异质性。通过孟德尔-埃格截距检验和 MR-PRESSO 评估多效性。最后，进行留一法分析以评估孟德尔随机化结果的稳健性。我们发现，最后一次生育年龄对乳腺癌有负向因果效应（OR = 0.687，95%CI = 0.539 - 0.875，P = 0.002），绝经年龄对乳腺癌有正向因果效应（OR = 1.054，95%CI = 1.034 - 1.075，P = 8.010×10⁻⁴）。此外，初潮年龄（OR = 0.977，95%CI = 0.915 - 1.043，P = 0.484）、首次性交年龄（OR = 1.053，95%CI = 0.958 - 1.157，P = 0.284）和首次生育年龄（OR = 0.981，95%CI = 0.936 - 1.027，P = 0.404）对乳腺癌均无影响。所有这些结果均可靠且稳定。总之，本研究表明，最后生育年龄较小和绝经年龄较大可能会增加患乳腺癌的风险。
