A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization.
A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization.
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DOI：
10.1038/s41467-020-20368-w
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发表时间：
2021-01-11
影响因子：
16.6
通讯作者：
MacGregor S
中科院分区：
文献类型：
--
作者：
Ong JS;Dixon-Suen SC;Han X;An J;Esophageal Cancer Consortium;23 and Me Research Team;Liyanage U;Dusingize JC;Schumacher J;Gockel I;Böhmer A;Jankowski J;Palles C;O'Mara T;Spurdle A;Law MH;Iles MM;Pharoah P;Berchuck A;Zheng W;Thrift AP;Olsen C;Neale RE;Gharahkhani P;Webb PM;MacGregor S
以前关于25-羟基维生素D(25(OH)D)与癌症的孟德尔随机化(MR)研究通常采用了几个变体，发现25(OH)D与癌症之间没有关系；然而，水平多效性的问题不能得到可靠的解决。使用与25(OH)D相关的更大一组变异(74个SNPs，高于之前的6个)，我们进行了统一的MR分析，以重新评估25(OH)D与10种癌症之间的关系。我们的发现与之前的MR研究基本一致，除了卵巢癌(OR0.89；95%C.I.：0.82至0.96每1 SD改变25(OH)D浓度)和基底细胞癌(OR1.16；95%C.I.：1.04至1.28)。然而，在多变量MR框架中调整了色素沉着相关变量后，基底细胞癌的发现减弱了。在这里，我们报告了低25(OH)D不太可能是大多数癌症的原因风险因素，我们的研究提供了比以前可能的更精确的可信区间。维生素D与癌症风险之间的遗传关联的研究通常力度不够。在这里，作者使用孟德尔随机化方法对此进行了分析，从英国生物库获得了70多种维生素D变体，并从各种联盟获得了大规模数据，证实了维生素D与大多数癌症之间的零关联。
Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible. Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.
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影响因子：
2
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan N;Thompson J
通讯作者：
Thompson J
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
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：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
3.5
作者：
Ahn J;Yu K;Stolzenberg-Solomon R;Simon KC;McCullough ML;Gallicchio L;Jacobs EJ;Ascherio A;Helzlsouer K;Jacobs KB;Li Q;Weinstein SJ;Purdue M;Virtamo J;Horst R;Wheeler W;Chanock S;Hunter DJ;Hayes RB;Kraft P;Albanes D
通讯作者：
Albanes D