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Abstract：
BACKGROUND: Numerous observational studies have investigated the potential link between hypertensive disorders of pregnancy (HDPs) and the subsequent risks of gynecologic tumors, yet the findings have been inconsistent. In this study, we utilized Mendelian randomization (MR) approach to assess the influence of HDPs on the future risks of ovarian, cervical, endometrial, and breast cancer and uterine fibroids, controlling for confounding factors.
METHODS: The genome-wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR-Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM).
RESULTS: Our univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM.
CONCLUSIONS: We discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.
METHODS: The genome-wide association studies (GWAS) summary data relevant to HDPs was obtained from the FinnGen databases (10,736 cases and 136,325 controls). Gynecologic tumor outcomes were extracted from the IEU Open GWAS project and UK Biobank (47,690 cases and 1, 092,073 controls). The inverse variance weighted (IVW) approach was selected as the principal method for MR analysis, supplemented by MR-Egger, weighted median, weighted model, simple model methods, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out method. Multivariate MR (MVMR) analysis was conducted after adjusting systolic blood pressure (SBP), body mass index (BMI) and type 2 diabetes mellitus (T2DM).
RESULTS: Our univariate MR analysis (UVMR) results revealed no significant relationship between HDPs and the risks of ovarian cancer (odds ratio [OR] = 0.924, p = 0.360), cervical cancer (OR = 1.230, p = 0.738), endometrial cancer (OR = 1.006, p = 0.949), uterine fibroids (OR = 1.155, p = 0.158), and breast cancer (OR = 0.792, p = 0.241) by IVW test. Similar results were observed in gestational hypertension and preeclampsia/eclampsia. Additionally, our study detected neither heterogeneity nor pleiotropy. MVMR analysis also provided no evidence of a causal association between HDPs and common gynecologic tumors after adjusting SBP, BMI, and T2DM.
CONCLUSIONS: We discovered no causal relationship between HDPs and ovarian, cervical, endometrial, breast cancer, and uterine fibroids in European populations. However, present analysis did not explore the effect of HDPs on the subtypes of gynecologic tumors across varied ethnic populations, which may require additional research.
摘要：
背景：许多观察性研究已经调查了妊娠高血压疾病（HDP）与随后的妇科肿瘤风险之间的潜在联系，然而，调查结果并不一致。在这项研究中,我们利用孟德尔随机化（MR）方法来评估HDPs对未来卵巢风险的影响，子宫颈,子宫内膜,乳腺癌和子宫肌瘤，控制混杂因素。
方法：与HDP相关的全基因组关联研究（GWAS）汇总数据来自FinnGen数据库（10,736例和136,325例对照）。从IEUOpenGWAS项目和UKBiobank中提取妇科肿瘤结果（47,690例和1,092,073例对照）。选择逆方差加权(IVW)方法作为MR分析的主要方法，由MR-Egger补充，加权中位数，加权模型，简单的模型方法，MR多效性残差和异常值(MR-PRESSO)测试，和留一法。调整收缩压（SBP）后进行多因素MR（MVMR）分析，体重指数（BMI）与2型糖尿病（T2DM）。
结果：我们的单变量MR分析（UVMR）结果显示，HDPs与卵巢癌风险之间没有显着关系（比值比[OR]=0.924，p=0.360），宫颈癌（OR=1.230，p=0.738），子宫内膜癌（OR=1.006，p=0.949），子宫肌瘤（OR=1.155，p=0.158），通过IVW测试，乳腺癌（OR=0.792，p=0.241）。在妊娠高血压和先兆子痫/子痫中观察到类似的结果。此外,我们的研究既没有发现异质性,也没有发现多效性.在调整SBP后，MVMR分析也没有提供HDPs与常见妇科肿瘤之间因果关系的证据。BMI,和T2DM。
结论：我们发现HDPs与卵巢之间没有因果关系，子宫颈,子宫内膜,乳腺癌,和欧洲人群的子宫肌瘤。然而,目前的分析没有探讨HDPs对不同种族人群妇科肿瘤亚型的影响，这可能需要更多的研究。
方法：与HDP相关的全基因组关联研究（GWAS）汇总数据来自FinnGen数据库（10,736例和136,325例对照）。从IEUOpenGWAS项目和UKBiobank中提取妇科肿瘤结果（47,690例和1,092,073例对照）。选择逆方差加权(IVW)方法作为MR分析的主要方法，由MR-Egger补充，加权中位数，加权模型，简单的模型方法，MR多效性残差和异常值(MR-PRESSO)测试，和留一法。调整收缩压（SBP）后进行多因素MR（MVMR）分析，体重指数（BMI）与2型糖尿病（T2DM）。
结果：我们的单变量MR分析（UVMR）结果显示，HDPs与卵巢癌风险之间没有显着关系（比值比[OR]=0.924，p=0.360），宫颈癌（OR=1.230，p=0.738），子宫内膜癌（OR=1.006，p=0.949），子宫肌瘤（OR=1.155，p=0.158），通过IVW测试，乳腺癌（OR=0.792，p=0.241）。在妊娠高血压和先兆子痫/子痫中观察到类似的结果。此外,我们的研究既没有发现异质性,也没有发现多效性.在调整SBP后，MVMR分析也没有提供HDPs与常见妇科肿瘤之间因果关系的证据。BMI,和T2DM。
结论：我们发现HDPs与卵巢之间没有因果关系，子宫颈,子宫内膜,乳腺癌,和欧洲人群的子宫肌瘤。然而,目前的分析没有探讨HDPs对不同种族人群妇科肿瘤亚型的影响，这可能需要更多的研究。
