观察性研究表明，基础代谢率(BMR)与子宫内膜癌(EC)和卵巢癌(OC)的风险有关联。然而，这些关联是否反映了因果关系尚不清楚。为了揭示BMR与EC和OC之间的因果关系，我们进行了第一次全面的两个样本门冬氨酸随机化(MR)分析。遗传变异被用作BMR的代理。 GWAS摘要统计数据从英国生物库联盟、子宫内膜癌协会联盟和卵巢癌协会联盟获得。反向方差加权方法被作为MR分析的主要方法。实施了一系列敏感性分析来验证结果的稳健性和可靠性。BMR与EC (ORSD=1.49；95% CI：1.29-1.72；p-Value< 0.001)和OC (ORSD=1.21；95% CI：1.08-1.35；p-Value< 0.001)的风险增加有显著关联。此外，分层分析表明，BMR与子宫内膜内皮癌(EEC)(ORSD=1.45；95% CI，1.23-1.70；p-Value< 0.001)，透明细胞卵巢癌(CCOC)(ORSD=1.89；95% CI：1.35-2.64；p-Value< 0.001)和子宫内膜内皮样卵巢癌风险(EOC)(ORSD=1.45；95% CI:1.12-1.88；p-Value = 0.005)呈正相关。然而，BMR与浸润性黏液性卵巢癌(IMOC)、高分化浆液性卵巢癌(HGSOC)和低分化浆液性卵巢癌(LGSOC)不存在显著的关联。上述结果的稳健性在敏感性分析中得到了进一步验证。MR研究为BMR与EC、EEC、OC、CCOC和EOC的风险正相关提供了病因证据。但是该研究没有提供足够的证据表明BMR与IMOC、HGSOC和LGSOC之间存在因果关系。本文受版权保护。版权所有。

Observational studies have demonstrated that basal metabolic rate (BMR) is associated with the risk of endometrial cancer (EC) and ovarian cancer (OC). However, it is unclear whether these associations reflect a causal relationship.To reveal the causality between BMR and EC and OC, we performed the first comprehensive two-sample Mendelian randomization (MR) analyses.Genetic variants were used as proxies of BMR. GWAS summary statistics of BMR, EC, and OC were obtained from the UK Biobank Consortium, Endometrial Cancer Association Consortium, and Ovarian Cancer Association Consortium, respectively. The inverse variance weighted method was employed as the main approach for MR analysis. A series of sensitivity analyses were implemented to validate the robustness and reliability of the results.BMR was significantly related to an increased risk of EC (ORSD = 1.49; 95%CI: 1.29-1.72; p-Value < 0.001) and OC (ORSD = 1.21; 95%CI:1.08-1.35; p-Value < 0.001). Furthermore, the stratified analysis indicated that BMR was positively associated with endometrioid endometrial cancer (EEC) (ORSD = 1.45; 95%CI, 1.23-1.70; p-Value < 0.001), clear cell ovarian cancer(CCOC) (ORSD = 1.89; 95%CI:1.35-2.64; p-Value < 0.001) and endometrioid ovarian cancer risk (EOC) (ORSD = 1.45; 95%CI:1.12-1.88; p-Value = 0.005). However, there were no significant associations of BMR with invasive mucinous ovarian cancer (IMOC), high grade serous ovarian cancer (HGSOC), and low grade serous ovarian cancer (LGSOC). The robustness of the above results was further verified in sensitivity analyses.The MR study provided etiological evidence for the positive association of BMR with the risk of EC, EEC, OC, CCOC, and EOC. But this study did not provide enough evidence suggesting the causal associations of BMR with IMOC, HGSOC, and LGSOC.This article is protected by copyright. All rights reserved.