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Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk

Shu, Xiang (författare)
Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
Chen, Zhishan (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
Long, Jirong (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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Guo, Xingyi (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
Yang, Yaohua (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
Qu, Conghui (författare)
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Ahn, Yoon-Ok (författare)
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
Cai, Qiuyin (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
Casey, Graham (författare)
Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States
Gruber, Stephen B. (författare)
Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States
Huyghe, Jeroen R. (författare)
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Jee, Sun Ha (författare)
Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea
Jenkins, Mark A. (författare)
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, VIC, Melbourne, Australia
Jia, Wei-Hua (författare)
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China
Jung, Keum Ji (författare)
Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea
Kamatani, Yoichiro (författare)
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan; Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
Kim, Dong-Hyun (författare)
Department of Social and Preventive Medicine, Hallym University College of Medicine, Chucheon, South Korea
Kim, Jeongseon (författare)
Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea
Kweon, Sun-Seog (författare)
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea
Le Marchand, Loic (författare)
University of Hawaii Cancer Center, HI, Honolulu, United States
Matsuda, Koichi (författare)
Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
Matsuo, Keitaro (författare)
Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Newcomb, Polly A. (författare)
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; School of Public Health, University of Washington, WA, Seattle, United States
Oh, Jae Hwan (författare)
Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Gyeonggi-do, South Korea
Ose, Jennifer (författare)
Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States
Oze, Isao (författare)
Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
Pai, Rish K. (författare)
Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States
Pan, Zhi-Zhong (författare)
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China
Pharoah, Paul D.P. (författare)
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
Playdon, Mary C. (författare)
Cancer Control and Population Sciences, Huntsman Cancer Institute, Department of Nutrition and Integrative Physiology, University of Utah, UT, Salt Lake City, United States; Department of Nutrition and Integrative Physiology, College of Health, University of Utah, UT, Salt Lake City, United States
Ren, Ze-Fang (författare)
School of Public Health, Sun Yat-sen University, Guangzhou, China
Schoen, Robert E. (författare)
Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States
Shin, Aesun (författare)
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea
Shin, Min-Ho (författare)
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea
Shu, Xiao-Ou (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
Sun, Xiaohui (författare)
Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, NY, New York, United States; Department of Epidemiology, Zhejiang Chinese Medical University, Zhejiang, China
Tangen, Catherine M. (författare)
SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
Tanikawa, Chizu (författare)
Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Ulrich, Cornelia M. (författare)
Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
van Duijnhoven, Franzel J.B. (författare)
Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands
van Guelpen, Bethany (författare)
Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi
Wolk, Alicja (författare)
Karolinska Institutet
Woods, Michael O. (författare)
Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada
Wu, Anna H. (författare)
University of Southern California, Preventative Medicine, CA, Los Angeles, United States
Peters, Ulrike (författare)
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States
Zheng, Wei (författare)
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, TN, Nashville, United States
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 (creator_code:org_t)
American Association for Cancer Research, 2022
2022
Engelska.
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:6, s. 1216-1226
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: The etiology of colorectal cancer is not fully understood.Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 > 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis.Results: Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini-Hochberg FDR (BH-FDR) < 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10-8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR < 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60−2.36, P = 2.6 × 10-11; OREUR: 1.01, 95% CI, 0.99−1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het < 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer.Conclusions: This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data.Impact: The identified metabolites could be developed into new tools for risk assessment of colorectal cancer in both European and EA populations.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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