ArticleGastroenterology2016
Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk.
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In one paragraph
Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 8 of them syntheses that pooled it.
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80citing papers in PubMed, 8 pooled it
14.4field-weighted citation impact, top 1% of its field
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Who cites it
80 citing papers in PubMed, 8 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Developing and validating polygenic risk scores for colorectal cancer risk prediction in East Asians.International journal of cancer · 2022Pooled it
- Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Pooled it
- Pooled it
- Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants.Nature communications · 2020Pooled it
- Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.Gastroenterology · 2019Pooled it
- Discovery of common and rare genetic risk variants for colorectal cancer.Nature genetics · 2019Pooled it
- Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.International journal of cancer · 2018Pooled it
- Correlation between polymorphism of vitamin D receptor TaqI and susceptibility to colorectal cancer: A meta-analysis.Medicine · 2017Pooled it
- Calcium and TRPML-Mediated Autophagy: Implications in Cancer, Cardiovascular Diseases, and Cardio-Oncology.Cardiovascular toxicology · 2026Review
- MyGeneRisk Colon: A Web-Based Tool for Personalized Colorectal Cancer Risk Prediction Based on Genetics and Lifestyle.medRxiv : the preprint server for health sciences · 2026Article
- A Swedish Haplotype GWAS in Familial and Sporadic Site-Specific Colorectal Cancer.International journal of molecular sciences · 2026Article
- Systematic analysis of functional genetic and epigenetic variants in colorectal cancer.Science advances · 2026Article
- Three-dimensional genome landscape of primary human cancers.Nature genetics · 2025Article
- Periodic tryptophan protein 1 promotes colorectal cancer growth via ribosome biogenesis.International journal of clinical oncology · 2025Article
- Patient Perspectives on Personalized Risk Communication Using Polygenic Risk Scores to Inform Colorectal Cancer Screening Decisions.AJPM focus · 2025Article
- Systematic functional interrogation of genome-wide association studies locus 17p13.3 deciphered role and genetic control of FAM57A in colorectal cancer development.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Genetic association and functional implications of TLR4 rs1927914 polymorphism on colon cancer risk.BMC cancer · 2024Article
- Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.British journal of cancer · 2024Article
- Urocortin-1 promotes colorectal cancer cell migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway.Journal of cancer research and clinical oncology · 2024Article
- A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.Human molecular genetics · 2024Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors at 20 institutions in 7 countries.
Chenjie ZengDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Koichi MatsudaLaboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Wei-Hua JiaState Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Jiang ChangState Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Sun-Seog KweonDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea; Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
Yong-Bing XiangDepartment of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Aesun ShinMolecular Epidemiology Branch, National Cancer Center, Goyang-si, South Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Sun Ha JeeInstitute for Health Promotion, Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Dong-Hyun KimDepartment of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
Ben ZhangDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Qiuyin CaiDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Xingyi GuoDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Jirong LongDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Nan WangDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; General Department, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Regina CourtneyDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Zhi-Zhong PanState Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Chen WuState Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Atsushi TakahashiRIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Min-Ho ShinDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
Keitaro MatsuoDivision of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
Fumihiko MatsudaCenter for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yu-Tang GaoDepartment of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Jae Hwan OhCenter for Colorectal Cancer, National Cancer Center, Goyang-si, South Korea.
Soriul KimInstitute for Health Promotion, Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Keum Ji JungInstitute for Health Promotion, Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
Yoon-Ok AhnDepartment of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Zefang RenSchool of Public Health, Sun Yat-sen University, Guangzhou, China.
Hong-Lan LiDepartment of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
Jie WuDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Jiajun ShiDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Wanqing WenDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Gong YangDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Bingshan LiDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Bu-Tian JiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO)
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Robert E SchoenDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Sébastien KüryCHU Nantes, Service de Génétique Médicale, Nantes, France.
Colorectal Transdisciplinary (CORECT) Study
Stephen B GruberUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Fredrick R SchumacherUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Stephanie L StenzelUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Colon Cancer Family Registry (CCFR)
Graham CaseyUSC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
John L HopperCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
Mark A JenkinsCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
Hyeong-Rok KimDepartment of Surgery, Chonnam National University Medical School, Gwangju, South Korea.
Jin-Young JeongDepartment of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
Ji Won ParkCenter for Colorectal Cancer, National Cancer Center, Goyang-si, South Korea; Department of Surgery, Seoul National University Hospital, Seoul, South Korea.
Kazuo TajimaDepartment of Public Health and Occupational Medicine, Mie University Graduate School of Medicine, Mie, Japan.
Sang-Hee ChoDepartment of Hemato-oncology, Chonnam National University Medical School, Gwangju, South Korea.
Michiaki KuboRIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Dongxin LinState Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yi-Xin ZengState Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: wei.zheng@vanderbilt.edu.
University of Southern California · USVanderbilt University · USThe University of Melbourne · AUChonnam National University Hospital · KRChinese Academy of Medical Sciences & Peking Union Medical College · CNGénétique Médicale & Génomique Fonctionelle · FRSun Yat-sen University · CNGerman Cancer Research Center · DEHallym University · KRMie University · JPShanghai Cancer Institute · CNYonsei University · KRRIKEN Center for Integrative Medical Sciences · JPSeoul National University · KRUniversity of Pittsburgh Medical Center · USAichi Cancer Center · JPKyoto University · JPNational Cancer Center · USNational Cancer Center · KRNational Cancer Institute · US
Funding
USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Saul Priceman · 1985 to 2026
$181.4MTumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jin Chen · 1995 to 2026
$172.8MStatistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER · 2000 to 2019
$77.8MUniversity of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Xin Chen · 1996 to 2026
$56.2MValidity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI WILLETT, WALTER C. · 1991 to 2009
$41.8MUnderstanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SICINSKA, · 2007 to 2023
$33.2MJH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MMolecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8MUSC Consortium:Colorectal Cancer Family RegistryU01CA074799 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAILE, ROBERT WILLIAM · 1997 to 2008
$20.4MUniversity of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4MIntramural NIH HHS Z01 CP010200NCI NIH HHS K05 CA154337NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA071789NCI NIH HHS P50 CA095103NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA042182NCI NIH HHS R01 CA048998NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA064277NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA081488NCI NIH HHS R01 CA082729NCI NIH HHS R01 CA092585NCI NIH HHS R01 CA124558NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA148667NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA188214NCI NIH HHS R37 CA070867NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA074799NCI NIH HHS U01 CA074800NCI NIH HHS U01 CA074806NCI NIH HHS U01 CA097735NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA164930NCI NIH HHS U19 CA148107NCI NIH HHS UM1 CA167551NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA173640NCI NIH HHS UM1 CA182910NCI NIH HHS UM1 CA186107NHGRI NIH HHS T32 HG000040NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNIA NIH HHS HHSN271201100004CNIEHS NIH HHS T32 ES013678WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
Abstract
BACKGROUND &
aimsKnown genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study to identify risk loci for CRC.
methodsThis discovery stage included 8027 cases and 22,577 controls of East-Asian ancestry. Promising variants were evaluated in studies including as many as 11,044 cases and 12,047 controls. Tumor-adjacent normal tissues from 188 patients were analyzed to evaluate correlations of risk variants with expression levels of nearby genes. Potential functionality of risk variants were evaluated using public genomic and epigenomic databases.
resultsWe identified 4 loci associated with CRC risk; P values for the most significant variant in each locus ranged from 3.92 × 10(-8) to 1.24 × 10(-12): 6p21.1 (rs4711689), 8q23.3 (rs2450115, rs6469656), 10q24.3 (rs4919687), and 12p13.3 (rs11064437). We also identified 2 risk variants at loci previously associated with CRC: 10q25.2 (rs10506868) and 20q13.3 (rs6061231). These risk variants, conferring an approximate 10%-18% increase in risk per allele, are located either inside or near protein-coding genes that include transcription factor EB (lysosome biogenesis and autophagy), eukaryotic translation initiation factor 3, subunit H (initiation of translation), cytochrome P450, family 17, subfamily A, polypeptide 1 (steroidogenesis), splA/ryanodine receptor domain and SOCS box containing 2 (proteasome degradation), and ribosomal protein S2 (ribosome biogenesis). Gene expression analyses showed a significant association (P < .05) for rs4711689 with transcription factor EB, rs6469656 with eukaryotic translation initiation factor 3, subunit H, rs11064437 with splA/ryanodine receptor domain and SOCS box containing 2, and rs6061231 with ribosomal protein S2.
conclusionsWe identified susceptibility loci and genes associated with CRC risk, linking CRC predisposition to steroid hormone, protein synthesis and degradation, and autophagy pathways and providing added insight into the mechanism of CRC pathogenesis.
Indexed as
Genetic LociGenetic Predisposition to DiseaseAdultAgedAsian PeopleBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCase-Control StudiesColorectal NeoplasmsEukaryotic Initiation Factor-3FemaleGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideQb-SNARE ProteinsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCYP17A1 protein, humanEukaryotic Initiation Factor-3Qb-SNARE ProteinsRibosomal Proteinsribosomal protein S21Steroid 17-alpha-HydroxylaseSuppressor of Cytokine Signaling ProteinsTFEB protein, humanVTI1A protein, humanColon CancerEpidemiologyeQTLSingle Nucleotide Polymorphisms
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