Literature DB >> 35266989

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

Xiang Shu1,2, Zhishan Chen2, Jirong Long2, Xingyi Guo2, Yaohua Yang2, Conghui Qu3, Yoon-Ok Ahn4, Qiuyin Cai2, Graham Casey5, Stephen B Gruber6, Jeroen R Huyghe3, Sun Ha Jee7, Mark A Jenkins8, Wei-Hua Jia9, Keum Ji Jung7, Yoichiro Kamatani10,11, Dong-Hyun Kim12, Jeongseon Kim13, Sun-Seog Kweon14, Loic Le Marchand15, Koichi Matsuda16, Keitaro Matsuo17,18, Polly A Newcomb3,19, Jae Hwan Oh20, Jennifer Ose21, Isao Oze17, Rish K Pai22, Zhi-Zhong Pan9, Paul D P Pharoah23, Mary C Playdon24,25, Ze-Fang Ren26, Robert E Schoen27, Aesun Shin4,28, Min-Ho Shin14, Xiao-Ou Shu2, Xiaohui Sun1,29, Catherine M Tangen30, Chizu Tanikawa31, Cornelia M Ulrich17, Franzel J B van Duijnhoven32, Bethany Van Guelpen33,34, Alicja Wolk35, Michael O Woods36, Anna H Wu37, Ulrike Peters3,38, Wei Zheng2.   

Abstract

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. ©2022 American Association for Cancer Research.

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Year:  2022        PMID: 35266989      PMCID: PMC9354799          DOI: 10.1158/1055-9965.EPI-21-1008

Source DB:  PubMed          Journal:  Cancer Epidemiol Biomarkers Prev        ISSN: 1055-9965            Impact factor:   4.090


  60 in total

1.  Metabolite profiles and the risk of developing diabetes.

Authors:  Thomas J Wang; Martin G Larson; Ramachandran S Vasan; Susan Cheng; Eugene P Rhee; Elizabeth McCabe; Gregory D Lewis; Caroline S Fox; Paul F Jacques; Céline Fernandez; Christopher J O'Donnell; Stephen A Carr; Vamsi K Mootha; Jose C Florez; Amanda Souza; Olle Melander; Clary B Clish; Robert E Gerszten
Journal:  Nat Med       Date:  2011-03-20       Impact factor: 53.440

2.  Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study.

Authors:  Wegene Borena; Tanja Stocks; Håkan Jonsson; Susanne Strohmaier; Gabriele Nagel; Tone Bjørge; Jonas Manjer; Göran Hallmans; Randi Selmer; Martin Almquist; Christel Häggström; Anders Engeland; Steinar Tretli; Hans Concin; Alexander Strasak; Pär Stattin; Hanno Ulmer
Journal:  Cancer Causes Control       Date:  2010-12-08       Impact factor: 2.506

3.  Cohort Profile: The Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology.

Authors:  Connie W Tsao; Ramachandran S Vasan
Journal:  Int J Epidemiol       Date:  2015-12       Impact factor: 7.196

4.  Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

Authors:  Stephanie L Schmit; Christopher K Edlund; Fredrick R Schumacher; Jian Gong; Tabitha A Harrison; Jeroen R Huyghe; Chenxu Qu; Marilena Melas; David J Van Den Berg; Hansong Wang; Stephanie Tring; Sarah J Plummer; Demetrius Albanes; M Henar Alonso; Christopher I Amos; Kristen Anton; Aaron K Aragaki; Volker Arndt; Elizabeth L Barry; Sonja I Berndt; Stéphane Bezieau; Stephanie Bien; Amanda Bloomer; Juergen Boehm; Marie-Christine Boutron-Ruault; Hermann Brenner; Stefanie Brezina; Daniel D Buchanan; Katja Butterbach; Bette J Caan; Peter T Campbell; Christopher S Carlson; Jose E Castelao; Andrew T Chan; Jenny Chang-Claude; Stephen J Chanock; Iona Cheng; Ya-Wen Cheng; Lee Soo Chin; James M Church; Timothy Church; Gerhard A Coetzee; Michelle Cotterchio; Marcia Cruz Correa; Keith R Curtis; David Duggan; Douglas F Easton; Dallas English; Edith J M Feskens; Rocky Fischer; Liesel M FitzGerald; Barbara K Fortini; Lars G Fritsche; Charles S Fuchs; Manuela Gago-Dominguez; Manish Gala; Steven J Gallinger; W James Gauderman; Graham G Giles; Edward L Giovannucci; Stephanie M Gogarten; Clicerio Gonzalez-Villalpando; Elena M Gonzalez-Villalpando; William M Grady; Joel K Greenson; Andrea Gsur; Marc Gunter; Christopher A Haiman; Jochen Hampe; Sophia Harlid; John F Harju; Richard B Hayes; Philipp Hofer; Michael Hoffmeister; John L Hopper; Shu-Chen Huang; Jose Maria Huerta; Thomas J Hudson; David J Hunter; Gregory E Idos; Motoki Iwasaki; Rebecca D Jackson; Eric J Jacobs; Sun Ha Jee; Mark A Jenkins; Wei-Hua Jia; Shuo Jiao; Amit D Joshi; Laurence N Kolonel; Suminori Kono; Charles Kooperberg; Vittorio Krogh; Tilman Kuehn; Sébastien Küry; Andrea LaCroix; Cecelia A Laurie; Flavio Lejbkowicz; Mathieu Lemire; Heinz-Josef Lenz; David Levine; Christopher I Li; Li Li; Wolfgang Lieb; Yi Lin; Noralane M Lindor; Yun-Ru Liu; Fotios Loupakis; Yingchang Lu; Frank Luh; Jing Ma; Christoph Mancao; Frank J Manion; Sanford D Markowitz; Vicente Martin; Koichi Matsuda; Keitaro Matsuo; Kevin J McDonnell; Caroline E McNeil; Roger Milne; Antonio J Molina; Bhramar Mukherjee; Neil Murphy; Polly A Newcomb; Kenneth Offit; Hanane Omichessan; Domenico Palli; Jesus P Paredes Cotoré; Julyann Pérez-Mayoral; Paul D Pharoah; John D Potter; Conghui Qu; Leon Raskin; Gad Rennert; Hedy S Rennert; Bridget M Riggs; Clemens Schafmayer; Robert E Schoen; Thomas A Sellers; Daniela Seminara; Gianluca Severi; Wei Shi; David Shibata; Xiao-Ou Shu; Erin M Siegel; Martha L Slattery; Melissa Southey; Zsofia K Stadler; Mariana C Stern; Sebastian Stintzing; Darin Taverna; Stephen N Thibodeau; Duncan C Thomas; Antonia Trichopoulou; Shoichiro Tsugane; Cornelia M Ulrich; Franzel J B van Duijnhoven; Bethany van Guelpan; Joseph Vijai; Jarmo Virtamo; Stephanie J Weinstein; Emily White; Aung Ko Win; Alicja Wolk; Michael Woods; Anna H Wu; Kana Wu; Yong-Bing Xiang; Yun Yen; Brent W Zanke; Yi-Xin Zeng; Ben Zhang; Niha Zubair; Sun-Seog Kweon; Jane C Figueiredo; Wei Zheng; Loic Le Marchand; Annika Lindblom; Victor Moreno; Ulrike Peters; Graham Casey; Li Hsu; David V Conti; Stephen B Gruber
Journal:  J Natl Cancer Inst       Date:  2019-02-01       Impact factor: 13.506

5.  Association analyses identify 31 new risk loci for colorectal cancer susceptibility.

Authors:  Philip J Law; Maria Timofeeva; Ceres Fernandez-Rozadilla; Peter Broderick; James Studd; Juan Fernandez-Tajes; Susan Farrington; Victoria Svinti; Claire Palles; Giulia Orlando; Amit Sud; Amy Holroyd; Steven Penegar; Evropi Theodoratou; Peter Vaughan-Shaw; Harry Campbell; Lina Zgaga; Caroline Hayward; Archie Campbell; Sarah Harris; Ian J Deary; John Starr; Laura Gatcombe; Maria Pinna; Sarah Briggs; Lynn Martin; Emma Jaeger; Archana Sharma-Oates; James East; Simon Leedham; Roland Arnold; Elaine Johnstone; Haitao Wang; David Kerr; Rachel Kerr; Tim Maughan; Richard Kaplan; Nada Al-Tassan; Kimmo Palin; Ulrika A Hänninen; Tatiana Cajuso; Tomas Tanskanen; Johanna Kondelin; Eevi Kaasinen; Antti-Pekka Sarin; Johan G Eriksson; Harri Rissanen; Paul Knekt; Eero Pukkala; Pekka Jousilahti; Veikko Salomaa; Samuli Ripatti; Aarno Palotie; Laura Renkonen-Sinisalo; Anna Lepistö; Jan Böhm; Jukka-Pekka Mecklin; Daniel D Buchanan; Aung-Ko Win; John Hopper; Mark E Jenkins; Noralane M Lindor; Polly A Newcomb; Steven Gallinger; David Duggan; Graham Casey; Per Hoffmann; Markus M Nöthen; Karl-Heinz Jöckel; Douglas F Easton; Paul D P Pharoah; Julian Peto; Federico Canzian; Anthony Swerdlow; Rosalind A Eeles; Zsofia Kote-Jarai; Kenneth Muir; Nora Pashayan; Andrea Harkin; Karen Allan; John McQueen; James Paul; Timothy Iveson; Mark Saunders; Katja Butterbach; Jenny Chang-Claude; Michael Hoffmeister; Hermann Brenner; Iva Kirac; Petar Matošević; Philipp Hofer; Stefanie Brezina; Andrea Gsur; Jeremy P Cheadle; Lauri A Aaltonen; Ian Tomlinson; Richard S Houlston; Malcolm G Dunlop
Journal:  Nat Commun       Date:  2019-05-14       Impact factor: 14.919

6.  A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context.

Authors:  Apolline Gallois; Joel Mefford; Arthur Ko; Amaury Vaysse; Hanna Julienne; Mika Ala-Korpela; Markku Laakso; Noah Zaitlen; Päivi Pajukanta; Hugues Aschard
Journal:  Nat Commun       Date:  2019-10-21       Impact factor: 14.919

7.  Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.

Authors:  Yingchang Lu; Sun-Seog Kweon; Qiuyin Cai; Chizu Tanikawa; Xiao-Ou Shu; Wei-Hua Jia; Yong-Bing Xiang; Jeroen R Huyghe; Tabitha A Harrison; Jeongseon Kim; Aesun Shin; Dong-Hyun Kim; Keitaro Matsuo; Sun Ha Jee; Xingyi Guo; Wanqing Wen; Jiajun Shi; Bingshan Li; Nan Wang; Min-Ho Shin; Hong-Lan Li; Zefang Ren; Jae Hwan Oh; Isao Oze; Yoon-Ok Ahn; Keum Ji Jung; Jing Gao; Yu-Tang Gao; Zhi-Zhong Pan; Yoichiro Kamatani; Andrew T Chan; Andrea Gsur; Jochen Hampe; Loic Le Marchand; Li Li; Annika Lindblom; Victor Moreno; Polly A Newcomb; Kenneth Offit; Paul D P Pharoah; Franzel J B van Duijnhoven; Bethany Van Guelpen; Pavel Vodicka; Stephanie J Weinstein; Alicja Wolk; Anna H Wu; Li Hsu; Yi-Xin Zeng; Jirong Long; Ulrike Peters; Koichi Matsuda; Wei Zheng
Journal:  Cancer Epidemiol Biomarkers Prev       Date:  2019-12-11       Impact factor: 4.254

8.  New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Authors:  Josée Dupuis; Claudia Langenberg; Inga Prokopenko; Richa Saxena; Nicole Soranzo; Anne U Jackson; Eleanor Wheeler; Nicole L Glazer; Nabila Bouatia-Naji; Anna L Gloyn; Cecilia M Lindgren; Reedik Mägi; Andrew P Morris; Joshua Randall; Toby Johnson; Paul Elliott; Denis Rybin; Gudmar Thorleifsson; Valgerdur Steinthorsdottir; Peter Henneman; Harald Grallert; Abbas Dehghan; Jouke Jan Hottenga; Christopher S Franklin; Pau Navarro; Kijoung Song; Anuj Goel; John R B Perry; Josephine M Egan; Taina Lajunen; Niels Grarup; Thomas Sparsø; Alex Doney; Benjamin F Voight; Heather M Stringham; Man Li; Stavroula Kanoni; Peter Shrader; Christine Cavalcanti-Proença; Meena Kumari; Lu Qi; Nicholas J Timpson; Christian Gieger; Carina Zabena; Ghislain Rocheleau; Erik Ingelsson; Ping An; Jeffrey O'Connell; Jian'an Luan; Amanda Elliott; Steven A McCarroll; Felicity Payne; Rosa Maria Roccasecca; François Pattou; Praveen Sethupathy; Kristin Ardlie; Yavuz Ariyurek; Beverley Balkau; Philip Barter; John P Beilby; Yoav Ben-Shlomo; Rafn Benediktsson; Amanda J Bennett; Sven Bergmann; Murielle Bochud; Eric Boerwinkle; Amélie Bonnefond; Lori L Bonnycastle; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Suzannah J Bumpstead; Guillaume Charpentier; Yii-Der Ida Chen; Peter Chines; Robert Clarke; Lachlan J M Coin; Matthew N Cooper; Marilyn Cornelis; Gabe Crawford; Laura Crisponi; Ian N M Day; Eco J C de Geus; Jerome Delplanque; Christian Dina; Michael R Erdos; Annette C Fedson; Antje Fischer-Rosinsky; Nita G Forouhi; Caroline S Fox; Rune Frants; Maria Grazia Franzosi; Pilar Galan; Mark O Goodarzi; Jürgen Graessler; Christopher J Groves; Scott Grundy; Rhian Gwilliam; Ulf Gyllensten; Samy Hadjadj; Göran Hallmans; Naomi Hammond; Xijing Han; Anna-Liisa Hartikainen; Neelam Hassanali; Caroline Hayward; Simon C Heath; Serge Hercberg; Christian Herder; Andrew A Hicks; David R Hillman; Aroon D Hingorani; Albert Hofman; Jennie Hui; Joe Hung; Bo Isomaa; Paul R V Johnson; Torben Jørgensen; Antti Jula; Marika Kaakinen; Jaakko Kaprio; Y Antero Kesaniemi; Mika Kivimaki; Beatrice Knight; Seppo Koskinen; Peter Kovacs; Kirsten Ohm Kyvik; G Mark Lathrop; Debbie A Lawlor; Olivier Le Bacquer; Cécile Lecoeur; Yun Li; Valeriya Lyssenko; Robert Mahley; Massimo Mangino; Alisa K Manning; María Teresa Martínez-Larrad; Jarred B McAteer; Laura J McCulloch; Ruth McPherson; Christa Meisinger; David Melzer; David Meyre; Braxton D Mitchell; Mario A Morken; Sutapa Mukherjee; Silvia Naitza; Narisu Narisu; Matthew J Neville; Ben A Oostra; Marco Orrù; Ruth Pakyz; Colin N A Palmer; Giuseppe Paolisso; Cristian Pattaro; Daniel Pearson; John F Peden; Nancy L Pedersen; Markus Perola; Andreas F H Pfeiffer; Irene Pichler; Ozren Polasek; Danielle Posthuma; Simon C Potter; Anneli Pouta; Michael A Province; Bruce M Psaty; Wolfgang Rathmann; Nigel W Rayner; Kenneth Rice; Samuli Ripatti; Fernando Rivadeneira; Michael Roden; Olov Rolandsson; Annelli Sandbaek; Manjinder Sandhu; Serena Sanna; Avan Aihie Sayer; Paul Scheet; Laura J Scott; Udo Seedorf; Stephen J Sharp; Beverley Shields; Gunnar Sigurethsson; Eric J G Sijbrands; Angela Silveira; Laila Simpson; Andrew Singleton; Nicholas L Smith; Ulla Sovio; Amy Swift; Holly Syddall; Ann-Christine Syvänen; Toshiko Tanaka; Barbara Thorand; Jean Tichet; Anke Tönjes; Tiinamaija Tuomi; André G Uitterlinden; Ko Willems van Dijk; Mandy van Hoek; Dhiraj Varma; Sophie Visvikis-Siest; Veronique Vitart; Nicole Vogelzangs; Gérard Waeber; Peter J Wagner; Andrew Walley; G Bragi Walters; Kim L Ward; Hugh Watkins; Michael N Weedon; Sarah H Wild; Gonneke Willemsen; Jaqueline C M Witteman; John W G Yarnell; Eleftheria Zeggini; Diana Zelenika; Björn Zethelius; Guangju Zhai; Jing Hua Zhao; M Carola Zillikens; Ingrid B Borecki; Ruth J F Loos; Pierre Meneton; Patrik K E Magnusson; David M Nathan; Gordon H Williams; Andrew T Hattersley; Kaisa Silander; Veikko Salomaa; George Davey Smith; Stefan R Bornstein; Peter Schwarz; Joachim Spranger; Fredrik Karpe; Alan R Shuldiner; Cyrus Cooper; George V Dedoussis; Manuel Serrano-Ríos; Andrew D Morris; Lars Lind; Lyle J Palmer; Frank B Hu; Paul W Franks; Shah Ebrahim; Michael Marmot; W H Linda Kao; James S Pankow; Michael J Sampson; Johanna Kuusisto; Markku Laakso; Torben Hansen; Oluf Pedersen; Peter Paul Pramstaller; H Erich Wichmann; Thomas Illig; Igor Rudan; Alan F Wright; Michael Stumvoll; Harry Campbell; James F Wilson; Richard N Bergman; Thomas A Buchanan; Francis S Collins; Karen L Mohlke; Jaakko Tuomilehto; Timo T Valle; David Altshuler; Jerome I Rotter; David S Siscovick; Brenda W J H Penninx; Dorret I Boomsma; Panos Deloukas; Timothy D Spector; Timothy M Frayling; Luigi Ferrucci; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson; Cornelia M van Duijn; Yurii S Aulchenko; Antonio Cao; Angelo Scuteri; David Schlessinger; Manuela Uda; Aimo Ruokonen; Marjo-Riitta Jarvelin; Dawn M Waterworth; Peter Vollenweider; Leena Peltonen; Vincent Mooser; Goncalo R Abecasis; Nicholas J Wareham; Robert Sladek; Philippe Froguel; Richard M Watanabe; James B Meigs; Leif Groop; Michael Boehnke; Mark I McCarthy; Jose C Florez; Inês Barroso
Journal:  Nat Genet       Date:  2010-01-17       Impact factor: 38.330

9.  Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study.

Authors:  Tilman Kühn; Anna Floegel; Disorn Sookthai; Theron Johnson; Ulrike Rolle-Kampczyk; Wolfgang Otto; Martin von Bergen; Heiner Boeing; Rudolf Kaaks
Journal:  BMC Med       Date:  2016-01-28       Impact factor: 8.775

10.  Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis.

Authors:  Hao Yu Chen; Benjamin J Cairns; Aeron M Small; Hannah A Burr; Athithan Ambikkumar; Andreas Martinsson; Sébastien Thériault; Hans Markus Munter; Brian Steffen; Richard Zhang; Rebecca T Levinson; Christian M Shaffer; Jian Rong; Emily Sonestedt; Line Dufresne; Johan Ljungberg; Ulf Näslund; Bengt Johansson; Dilrini K Ranatunga; Rachel A Whitmer; Matthew J Budoff; Albert Nguyen; Ramachandran S Vasan; Martin G Larson; William S Harris; Scott M Damrauer; Ken D Stark; S Matthijs Boekholdt; Nicholas J Wareham; Philippe Pibarot; Benoit J Arsenault; Patrick Mathieu; Vilmundur Gudnason; Christopher J O'Donnell; Jerome I Rotter; Michael Y Tsai; Wendy S Post; Robert Clarke; Stefan Söderberg; Yohan Bossé; Quinn S Wells; J Gustav Smith; Daniel J Rader; Mark Lathrop; James C Engert; George Thanassoulis
Journal:  JAMA Cardiol       Date:  2020-06-01       Impact factor: 30.154

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