Child and adult adiposity and subtype-specific endometrial cancer risk: a multivariable Mendelian randomisation study.
Child and adult adiposity and subtype-specific endometrial cancer risk: a multivariable Mendelian randomisation study.
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DOI：
10.1038/s41366-022-01231-y
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发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
Crosbie EJ
中科院分区：
文献类型：
--
作者：
Kennedy OJ;Bafligil C;O'Mara TA;Wang X;Evans DG;Kar S;Crosbie EJ
肥胖增加是子宫内膜癌（EC）的已知危险因素。本研究的目的是解开儿童和成人肥胖对成人EC风险的独立因果关系，包括使用多变量孟德尔随机化的类肥胖和非类肥胖组织学亚型。这些分析采用了来自英国生物银行的遗传关联作为儿童和成人体型的代理，其中12，906例病例和108，979例对照参与了子宫内膜癌协会联盟。在多变量分析中，成人体型增加了总体EC（OR 2.30，95% CI 1.73-3.06）和类风湿性EC风险（OR 2.28，95% CI 1.65-3.16），而儿童体型的影响极小。相比之下，儿童体型（OR 2.26，95% CI 1.03-4.99）而非成人体型会增加非类风湿性EC的风险。因此，儿童肥胖对成人肥胖介导的类肥胖EC风险有间接影响，但对非类肥胖EC风险有直接影响，与成人肥胖无关。这些新的发现表明，在生命的不同时期针对肥胖的干预措施在预防亚型特异性EC方面具有关键作用。
Increased adiposity is a known risk factor for endometrial cancer (EC). This study aimed to disentangle the separate causal roles of child and adult adiposity on EC risk in adults, including endometrioid and non-endometrioid histological subtypes using multivariable Mendelian randomisation. These analyses employed genetic associations derived from UK Biobank as proxies for child and adult body size in 12,906 cases and 108,979 controls that participated in the Endometrial Cancer Association Consortium. In multivariable analyses, adult body size increased overall EC (OR 2.30, 95% CI 1.73–3.06) and endometrioid EC risk (OR 2.28, 95% CI 1.65–3.16), while child body size had minimal effect. In contrast, child body size (OR 2.26, 95% CI 1.03–4.99) but not adult body size increased non-endometrioid EC risk. As such, child adiposity has an indirect effect on endometrioid EC risk that is mediated by adult adiposity but has a direct effect on non-endometrioid EC risk that is independent of adult adiposity. These novel findings indicate that interventions targeting adiposity during distinct periods in life have a critical role in preventing subtype-specific EC.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
--
作者：
Jaishuen, Atthapon;Kunakornporamat, Kate;Therasakvichya, Suwanit
通讯作者：
Therasakvichya, Suwanit
影响因子：
3.5
作者：
Hemani G;Bowden J;Davey Smith G
通讯作者：
Davey Smith G
影响因子：
8
作者：
Tobin, Laura M.;Mavinkurve, Meenal;O'Shea, Donal
通讯作者：
O'Shea, Donal
影响因子：
8.8
作者：
Weihe, Paul;Spielmann, Julia;Weihrauch-Blueher, Susann
通讯作者：
Weihrauch-Blueher, Susann