机构:[1]Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.[2]Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics &[3]Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK.[3]Centre for Global Health, Usher Institute, The University of Edinburgh, Edinburgh, UK.[4]Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics &[6]Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK.[5]Danish Institute for Advanced Study (DIAS), Department of Public Health, University of Southern Denmark, Odense, Denmark.[6]School of Public Health, Zhejiang University, Hangzhou, China.[7]Division of Genetics and Epidemiology, The Institute of Cancer Research, Surrey, UK.
Epidemiological evidence is consistent with a protective effect of vitamin D against colorectal cancer (CRC), but the observed strong associations are open to confounders and potential reverse causation. Previous Mendelian randomisation (MR) studies were limited by poor genetic instruments and inadequate statistical power. Moreover, whether genetically higher CRC risk can influence vitamin D level, namely the reverse causation, still remains unknown. Herein, we report the first bi-directional MR study. We employed 110 newly-identified genetic variants as proxies for vitamin D to obtain unconfounded effect estimates on CRC risk in 26 397 CRC cases and 41 481 controls of European ancestry. To test for reserve causation, we estimated effects of 115 CRC-risk variants on vitamin D level amongst 417 580 participants from the UK Biobank. The causal association was estimated using the random-effect inverse-variance weighted (IVW) method. We found no significant causal effect of vitamin D on CRC risk (IVW estimate OR: 0.97, 95%CI: 0.88-1.07, P = 0.565). Similarly, no significant reverse causal association was identified between genetically increased CRC risk and vitamin D levels (IVW estimate β: -0.002, 95% CI: -0.008 to 0.004, P = 0.543). Stratified analysis by tumour sites did not identify significant causal associations in either direction between vitamin D and colon or rectal cancer. Despite the improved statistical power of this study, we found no evidence of causal association of either direction between circulating vitamin D and CRC risk. Significant associations reported by observational studies may be primarily driven by unidentified confounders.This article is protected by copyright. All rights reserved.
基金:
This work was supported by CRUK programme
grant C348/A18927 (M. G. D.). It was also
supported by funding for the infrastructure and
staffing of the Edinburgh CRUK Cancer
Research Centre. E. T. was supported by a
CRUK Career Development Fellowship
(C31250/A22804). X. Z. is supported by The
Darwin Trust of Edinburgh. Y. H. and X. L. was
supported by the China Scholarship Council.
Y. H. was supported by the Henry Lester Trust
and The Great Britain-China Educational Trust.
The work received support from COST Action
BM1206.
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2021]版:
大类|1 区医学
小类|2 区肿瘤学
最新[2023]版:
大类|2 区医学
小类|2 区肿瘤学
第一作者:
第一作者机构:[1]Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.[2]Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics &
共同第一作者:
通讯作者:
通讯机构:[2]Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics &[3]Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK.[3]Centre for Global Health, Usher Institute, The University of Edinburgh, Edinburgh, UK.[4]Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics &[*1]Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.[*2]Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
推荐引用方式(GB/T 7714):
He Yazhou,Zhang Xiaomeng,Timofeeva Maria,et al.Bi-directional Mendelian randomisation analysis of the relationship between circulating vitamin D concentration and colorectal cancer risk.[J].International journal of cancer.2021,doi:10.1002/ijc.33779.
APA:
He Yazhou,Zhang Xiaomeng,Timofeeva Maria,Farrington Susan M,Li Xue...&Dunlop Malcolm G.(2021).Bi-directional Mendelian randomisation analysis of the relationship between circulating vitamin D concentration and colorectal cancer risk..International journal of cancer,,
MLA:
He Yazhou,et al."Bi-directional Mendelian randomisation analysis of the relationship between circulating vitamin D concentration and colorectal cancer risk.".International journal of cancer .(2021)