Colorectal cancer susceptibility loci and influence on survival
Nan Song
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
Nan Song and Kyeezu Kim contributed equally to this work and should be considered as co-first authors.Search for more papers by this authorKyeezu Kim
Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, Illinois
Nan Song and Kyeezu Kim contributed equally to this work and should be considered as co-first authors.Search for more papers by this authorCorresponding Author
Aesun Shin
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea
Aesun Shin and Jae Hwan Oh contributed equally to this work and should be considered as co-corresponding authors.Correspondence
Aesun Shin, Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
and
Jae Hwan Oh, Center for Colorectal Cancer, Hospital, National Cancer Center, 323 Ilsan-ro, Insandong-gu, Goyang, Gyeonggi-do 10408, South Korea.
Email: [email protected]
Search for more papers by this authorJi Won Park
Department of Surgery, Seoul National University College of Medicine and Hospital, Seoul, South Korea
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Search for more papers by this authorHee Jin Chang
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Search for more papers by this authorJiajun Shi
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Search for more papers by this authorQiuyin Cai
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Search for more papers by this authorDae Yong Kim
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Search for more papers by this authorWei Zheng
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Search for more papers by this authorCorresponding Author
Jae Hwan Oh
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Aesun Shin and Jae Hwan Oh contributed equally to this work and should be considered as co-corresponding authors.Correspondence
Aesun Shin, Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
and
Jae Hwan Oh, Center for Colorectal Cancer, Hospital, National Cancer Center, 323 Ilsan-ro, Insandong-gu, Goyang, Gyeonggi-do 10408, South Korea.
Email: [email protected]
Search for more papers by this authorNan Song
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
Nan Song and Kyeezu Kim contributed equally to this work and should be considered as co-first authors.Search for more papers by this authorKyeezu Kim
Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, Illinois
Nan Song and Kyeezu Kim contributed equally to this work and should be considered as co-first authors.Search for more papers by this authorCorresponding Author
Aesun Shin
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea
Aesun Shin and Jae Hwan Oh contributed equally to this work and should be considered as co-corresponding authors.Correspondence
Aesun Shin, Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
and
Jae Hwan Oh, Center for Colorectal Cancer, Hospital, National Cancer Center, 323 Ilsan-ro, Insandong-gu, Goyang, Gyeonggi-do 10408, South Korea.
Email: [email protected]
Search for more papers by this authorJi Won Park
Department of Surgery, Seoul National University College of Medicine and Hospital, Seoul, South Korea
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Search for more papers by this authorHee Jin Chang
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Search for more papers by this authorJiajun Shi
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Search for more papers by this authorQiuyin Cai
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Search for more papers by this authorDae Yong Kim
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Search for more papers by this authorWei Zheng
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Search for more papers by this authorCorresponding Author
Jae Hwan Oh
Center for Colorectal Cancer, National Cancer Center, Goyang, South Korea
Aesun Shin and Jae Hwan Oh contributed equally to this work and should be considered as co-corresponding authors.Correspondence
Aesun Shin, Department of Preventive Medicine, College of Medicine, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
and
Jae Hwan Oh, Center for Colorectal Cancer, Hospital, National Cancer Center, 323 Ilsan-ro, Insandong-gu, Goyang, Gyeonggi-do 10408, South Korea.
Email: [email protected]
Search for more papers by this authorAbstract
Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. To evaluate the potential influence of colorectal cancer susceptibility SNPs on disease prognosis, we investigated whether GWAS-identified colorectal cancer risk SNPs and polygenic risk scores (PRSs) might be associated with survival among colorectal cancer patients. A total of 1374 colorectal cancer patients were recruited from the Korean National Cancer Center. For genotyping, 30 colorectal cancer-susceptibility SNPs previously identified by GWAS were selected. The Cox proportional hazard model was used to evaluate associations of these risk SNPs and PRSs with disease-free survival (DFS) and overall survival (OS). The prognostic values were compared between genetic and nongenetic models using Harrell's c index. During the follow-up period (median: 88, 91 months for DFS and OS), 570 DFS (41.5%) and 487 OS (35.4%) events were observed. We found that 5 SNPs were significantly associated with DFS or OS among colorectal cancer patients at P < .05: rs10936599 at 3q26.2 (MYNN), rs704017 at 10q22.3 (ZMIZ1-AS1), rs11196172 at 10q25.2 (TCF7L2), rs3802842 at 11q23.1 (COLCA1-2), and rs9929218 at 16q22.1 (CDH1). The PRSs constructed using these 5 SNPs were associated with worse survival (DFS: Ptrend = .02 unweighted PRS, Ptrend = .01 weighted PRS, OS: Ptrend = 3.7 × 10−3 unweighted, Ptrend = .02 weighted PRS). Our results suggest that several colorectal cancer susceptibility SNPs might also be related to survival by influencing disease progression.
Supporting Information
| Filename | Description |
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| gcc22674-sup-0001-Figures.pptxPowerPoint 2007 presentation , 118.1 KB |
Supporting Information, Figure S1 Kaplan–Meier survival curves of colorectal cancer patients stratified by the number of unfavorable alleles of rs704017 and rs3802842. A, Disease-free survival. B, Overall survival Supporting Information, Figure S2. Kaplan–Meier survival curves of colorectal cancer patients stratified by the weighted polygenic risk score using rs704017 and rs3802842. A, Disease-free survival. B, Overall survival |
| gcc22674-sup-0002-Tables.docxWord 2007 document , 47.8 KB |
Supporting Information, Table S1 Associations between colorectal cancer susceptibility SNPs and survival of colorectal cancer patients by genetic model Supporting Information, Table S2. Associations between colorectal cancer susceptibility SNPs and risk of colorectal cancer patients by genetic model |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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