机构:[1]Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, People's Republic of China[2]Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics & Molecular Medicine, Western General Hospital, The University ofEdinburgh, Edinburgh, UK[3]Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, WesternGeneral Hospital, The University of Edinburgh, Edinburgh, UK[4]Centre for Global Health, Usher Institute, 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, People's Republic of China
Previous studies using additive genetic models failed to identify robust evidence of associations between colorectal cancer (CRC) risk variants and survival outcomes. However, additive models can be prone to false negative detection if the underlying inheritance mode is recessive. Here, we tested all currently known CRC-risk variants (n = 129) in a discovery analysis of 5675 patients from a Scottish cohort. Significant associations were then validated in 2474 CRC cases from UK Biobank. We found that the TT genotype of the intron variant rs7495132 in the CRTC3 gene was associated with clinically relevant poorer CRC-specific survival in both the discovery (HR = 1.97, 95% CI = 1.41-2.74, P = 6.1x10-5 ) and validation analysis (HR = 1.69, 95% CI = 1.03-2.79, P = 0.038). In addition, the GG genotype of rs10161980 (intronic variant of AL139383.1 lncRNA) was associated with worse overall survival in the discovery cohort (HR = 1.24, 95% CI = 1.10-1.39, P = 3.4x10-4 ) and CRC-specific survival in the validation cohort (HR = 1.26, 95% CI = 1.01-1.56, P = 0.040). Our findings show that common genetic risk factors can also influence CRC survival outcome. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
基金:
Cancer Research UK, Grant/Award Numbers:
C31250/A22804, C348/A18927; Darwin
Trust; China Scholarship Council; Henry Lester
Trust and the Great Britain China Educational
Trust; MRC Human Genetics Unit Centre
Grant, Grant/Award Numbers: U127527198,
U127527202; 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, People's Republic of China[2]Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics & Molecular Medicine, Western General Hospital, The University ofEdinburgh, Edinburgh, UK[3]Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, WesternGeneral Hospital, The University of Edinburgh, Edinburgh, UK[4]Centre for Global Health, Usher Institute, The University of Edinburgh, Edinburgh, UK
通讯作者:
通讯机构:[2]Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics & Molecular Medicine, Western General Hospital, The University ofEdinburgh, Edinburgh, UK[3]Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics & Molecular Medicine, WesternGeneral Hospital, The University of Edinburgh, Edinburgh, UK[4]Centre for Global Health, Usher Institute, The University of Edinburgh, Edinburgh, UK[*1]Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK[*2]Centre for Global Health Research, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK
推荐引用方式(GB/T 7714):
Yazhou He,Maria Timofeeva,Xiaomeng Zhang,et al.Colorectal cancer risk variants rs10161980 and rs7495132 are associated with cancer survival outcome by a recessive mode of inheritance.[J].International journal of cancer.2021,148(11):2774-2778.doi:10.1002/ijc.33465.
APA:
Yazhou He,Maria Timofeeva,Xiaomeng Zhang,Wei Xu,Xue Li...&Evropi Theodoratou.(2021).Colorectal cancer risk variants rs10161980 and rs7495132 are associated with cancer survival outcome by a recessive mode of inheritance..International journal of cancer,148,(11)
MLA:
Yazhou He,et al."Colorectal cancer risk variants rs10161980 and rs7495132 are associated with cancer survival outcome by a recessive mode of inheritance.".International journal of cancer 148..11(2021):2774-2778