{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:56:38Z","timestamp":1773716198415,"version":"3.50.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["GA825832 LEGACy"],"award-info":[{"award-number":["GA825832 LEGACy"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Gastric Cancer (GC) is the fourth most deadly cancer worldwide. Enhanced understanding of its key epidemiological and molecular drivers is urgently needed to lower the incidence and improve outcomes. Furthermore, tumor biology in European (EU) and Latin American (LATAM) countries is understudied. The LEGACy study is a Horizon 2020 funded multi-institutional research approach to 1) detail the epidemiological features including risk factors of GC in current time and 2) develop cost-effective methods to identify and integrate biological biomarkers needed to guide diagnostic and therapeutic approaches with the aim of filling the knowledge gap on GC in these areas.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This observational study has three parts that are conducted in parallel during 2019\u20132023 across recruiting centers from four EU and four LATAM countries: Part 1) A case-control study (800 cases and 800 controls) using questionnaires on candidate risk factors for GC, which will be correlated with clinical, demographic and epidemiological parameters. Part 2) A case-control tissue sampling study (400 cases and 400 controls) using proteome, genome, microbiome and immune analyses to characterize advanced (stage III and IV) GC. Patients in this part of the study will be followed over time to observe clinical outcomes. The first half of samples will be used as training cohort to identify the most relevant risk factors and biomarkers, which will be selected to propose cost-effective diagnostic and predictive methods that will be validated with the second half of samples. Part 3) An educational study, as part of our prevention strategy (subjects recruited from the general public) to test and disseminate knowledge on GC risk factors and symptoms by a questionnaire and informative video. Patients could be recruited for more than one of the three LEGACy studies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>The LEGACy study aims to generate novel, in-depth knowledge on the tumor biological characteristics through integrating epidemiological, multi-omics and clinical data from GC patients at an EU-LATAM partnership. During the study, cost-effective panels with potential use in clinical decision making will be developed and validated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> Identifiers:<\/jats:p>\n                <jats:p>Part 1: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03957031\">NCT03957031<\/jats:ext-link>.<\/jats:p>\n                <jats:p>Part 2: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04015466\">NCT04015466<\/jats:ext-link>.<\/jats:p>\n                <jats:p>Part 3: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04019808\">NCT04019808<\/jats:ext-link>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-022-09689-9","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T03:29:56Z","timestamp":1655090996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The LEGACy study: a European and Latin American consortium to identify risk factors and molecular phenotypes in gastric cancer to improve prevention strategies and personalized clinical decision making globally"],"prefix":"10.1186","volume":"22","author":[{"given":"Tessa Suzanne","family":"van Schooten","sequence":"first","affiliation":[]},{"given":"Sarah","family":"Derks","sequence":"additional","affiliation":[]},{"given":"Elena","family":"Jim\u00e9nez-Mart\u00ed","sequence":"additional","affiliation":[]},{"given":"Fatima","family":"Carneiro","sequence":"additional","affiliation":[]},{"given":"Ceu","family":"Figueiredo","sequence":"additional","affiliation":[]},{"given":"Erika","family":"Ruiz","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Alsina","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Molero","sequence":"additional","affiliation":[]},{"given":"Marcelo","family":"Garrido","sequence":"additional","affiliation":[]},{"given":"Arnoldo","family":"Riquelme","sequence":"additional","affiliation":[]},{"given":"Carmelo","family":"Caballero","sequence":"additional","affiliation":[]},{"given":"Eva","family":"Lezcano","sequence":"additional","affiliation":[]},{"given":"Juan Manuel","family":"O\u2019Connor","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Esteso","sequence":"additional","affiliation":[]},{"given":"Judith","family":"Farr\u00e9s","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Manuel","family":"Mas","sequence":"additional","affiliation":[]},{"given":"Florian","family":"Lordick","sequence":"additional","affiliation":[]},{"given":"Jeannette","family":"Vogt","sequence":"additional","affiliation":[]},{"given":"Antonella","family":"Cardone","sequence":"additional","affiliation":[]},{"given":"Charis","family":"Girvalaki","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9s","family":"Cervantes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2789-9082","authenticated-orcid":false,"given":"Tania","family":"Fleitas","sequence":"additional","affiliation":[]},{"name":"on behalf of the members of LEGACy consortium","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"issue":"3","key":"9689_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209\u201349. https:\/\/doi.org\/10.3322\/caac.21660.","journal-title":"CA Cancer J Clin"},{"issue":"5","key":"9689_CR2","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1158\/1055-9965.EPI-13-1057","volume":"23","author":"P Karimi","year":"2014","unstructured":"Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric Cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Prev Biomarkers. 2014;23(5):700\u201313. https:\/\/doi.org\/10.1158\/1055-9965.EPI-13-1057.","journal-title":"Cancer Epidemiol Prev Biomarkers"},{"key":"9689_CR3","doi-asserted-by":"publisher","unstructured":"Cunningham D, Starling N, Rao S, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008. https:\/\/doi.org\/10.1056\/NEJMoa073149.","DOI":"10.1056\/NEJMoa073149"},{"key":"9689_CR4","doi-asserted-by":"publisher","unstructured":"Smyth EC, Verheij M, Allum W, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016. https:\/\/doi.org\/10.1093\/annonc\/mdw350.","DOI":"10.1093\/annonc\/mdw350"},{"key":"9689_CR5","doi-asserted-by":"publisher","unstructured":"Asaka M, Mabe K. Strategies for eliminating death from gastric cancer in Japan. Proc Japan Acad Ser B Phys Biol Sci. 2014. https:\/\/doi.org\/10.2183\/pjab.90.251.","DOI":"10.2183\/pjab.90.251"},{"issue":"5","key":"9689_CR6","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1136\/gutjnl-2019-320234","volume":"69","author":"M Arnold","year":"2020","unstructured":"Arnold M, Park JY, Camargo MC, Lunet N, Forman D, Soerjomataram I. Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035. Gut. 2020;69(5):823\u20139. https:\/\/doi.org\/10.1136\/gutjnl-2019-320234.","journal-title":"Gut."},{"key":"9689_CR7","doi-asserted-by":"publisher","unstructured":"del P DM, Icaza G, Nu\u00f1ez L, Pou SA. Gastric Cancer mortality trends in the southern cone: disentangling age, period and cohort patterns in Argentina and Chile. Sci Rep. 2020;10(1). https:\/\/doi.org\/10.1038\/s41598-020-58539-w.","DOI":"10.1038\/s41598-020-58539-w"},{"issue":"2","key":"9689_CR8","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s10552-012-0110-z","volume":"24","author":"P Bonequi","year":"2013","unstructured":"Bonequi P, Meneses-Gonz\u00e1lez F, Correa P, Rabkin CS, Camargo MC. Risk factors for gastric cancer in Latin America: a meta-analysis. Cancer Causes Control. 2013;24(2):217\u201331. https:\/\/doi.org\/10.1007\/s10552-012-0110-z.","journal-title":"Cancer Causes Control"},{"issue":"1","key":"9689_CR9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1097\/CEJ.0000000000000017","volume":"24","author":"C Pelucchi","year":"2015","unstructured":"Pelucchi C, Lunet N, Boccia S, et al. The stomach cancer pooling (StoP) project: study design and presentation. Eur J Cancer Prev. 2015;24(1):16\u201323. https:\/\/doi.org\/10.1097\/CEJ.0000000000000017.","journal-title":"Eur J Cancer Prev"},{"issue":"6","key":"9689_CR10","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1093\/jnci\/djx262","volume":"110","author":"WF Anderson","year":"2018","unstructured":"Anderson WF, Rabkin CS, Turner N, Fraumeni JF, Rosenberg PS, Camargo MC. The changing face of noncardia gastric cancer incidence among US non-Hispanic whites. J Natl Cancer Inst. 2018;110(6):608\u201315. https:\/\/doi.org\/10.1093\/jnci\/djx262.","journal-title":"J Natl Cancer Inst"},{"key":"9689_CR11","doi-asserted-by":"publisher","unstructured":"Camargo MC, Garc\u00eda A, Riquelme A, et al. The problem of helicobacter pylori resistance to antibiotics: a systematic review in latin America. Am J Gastroenterol. 2014. https:\/\/doi.org\/10.1038\/ajg.2014.24.","DOI":"10.1038\/ajg.2014.24"},{"key":"9689_CR12","doi-asserted-by":"publisher","unstructured":"Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of helicobacter pylori infection: systematic review and Meta-analysis. Gastroenterology. 2017. https:\/\/doi.org\/10.1053\/j.gastro.2017.04.022.","DOI":"10.1053\/j.gastro.2017.04.022"},{"issue":"1","key":"9689_CR13","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/ajco.12112","volume":"10","author":"YJ Bang","year":"2014","unstructured":"Bang YJ, Yalcin S, Roth A, et al. Registry of gastric cancer treatment evaluation (REGATE): I baseline disease characteristics. Asia Pac J Clin Oncol. 2014;10(1):38\u201352. https:\/\/doi.org\/10.1111\/ajco.12112.","journal-title":"Asia Pac J Clin Oncol"},{"issue":"7517","key":"9689_CR14","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nature13480","volume":"513","author":"AJ Bass","year":"2014","unstructured":"Bass AJ, Thorsson V, Shmulevich I, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202\u20139. https:\/\/doi.org\/10.1038\/nature13480.","journal-title":"Nature."},{"issue":"7300","key":"9689_CR15","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/nature09167","volume":"465","author":"International network of cancer genome projects","year":"2010","unstructured":"International network of cancer genome projects. Nature. 2010;465(7300):966. https:\/\/doi.org\/10.1038\/nature09167.","journal-title":"Nature."},{"key":"9689_CR16","doi-asserted-by":"publisher","unstructured":"Zhang J, Baran J, Cros A, et al. International cancer genome consortium data portal-a one-stop shop for cancer genomics data. Database. 2011;2011. https:\/\/doi.org\/10.1093\/database\/bar026.","DOI":"10.1093\/database\/bar026"},{"key":"9689_CR17","doi-asserted-by":"publisher","unstructured":"Derks S, de Klerk LK, Xu X, et al. Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas. Ann Oncol. 2020. https:\/\/doi.org\/10.1016\/j.annonc.2020.04.011.","DOI":"10.1016\/j.annonc.2020.04.011"},{"issue":"15","key":"9689_CR18","doi-asserted-by":"publisher","first-page":"4441","DOI":"10.1158\/1078-0432.CCR-16-2211","volume":"23","author":"BH Sohn","year":"2017","unstructured":"Sohn BH, Hwang JE, Jang HJ, et al. Clinical significance of four molecular subtypes of gastric cancer identified by the Cancer genome atlas project. Clin Cancer Res. 2017;23(15):4441\u20139. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-2211.","journal-title":"Clin Cancer Res"},{"key":"9689_CR19","doi-asserted-by":"publisher","unstructured":"Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018. https:\/\/doi.org\/10.1038\/s41591-018-0101-z.","DOI":"10.1038\/s41591-018-0101-z"},{"key":"9689_CR20","doi-asserted-by":"publisher","unstructured":"Smyth EC, Wotherspoon A, Peckitt C, et al. Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council adjuvant gastric Infusional chemotherapy (MAGIC) trial. JAMA Oncol. 2017. https:\/\/doi.org\/10.1001\/jamaoncol.2016.6762.","DOI":"10.1001\/jamaoncol.2016.6762"},{"issue":"5","key":"9689_CR21","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.1002\/ijc.29210","volume":"136","author":"J Ferlay","year":"2015","unstructured":"Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359\u201386. https:\/\/doi.org\/10.1002\/ijc.29210.","journal-title":"Int J Cancer"},{"issue":"2","key":"9689_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3322\/caac.21388","volume":"67","author":"MB Amin","year":"2017","unstructured":"Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC Cancer staging manual: continuing to build a bridge from a population-based to a more \u201cpersonalized\u201d approach to cancer staging. CA Cancer J Clin. 2017;67(2):93\u20139. https:\/\/doi.org\/10.3322\/caac.21388.","journal-title":"CA Cancer J Clin"},{"issue":"2","key":"9689_CR23","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/13557858.2017.1398317","volume":"25","author":"SC Shah","year":"2020","unstructured":"Shah SC, Nunez H, Chiu S, et al. Low baseline awareness of gastric cancer risk factors amongst at-risk multiracial\/ethnic populations in new York City: results of a targeted, culturally sensitive pilot gastric cancer community outreach program. Ethn Health. 2020;25(2):189\u2013205. https:\/\/doi.org\/10.1080\/13557858.2017.1398317.","journal-title":"Ethn Health"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-022-09689-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-022-09689-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-022-09689-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T03:32:08Z","timestamp":1655091128000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-022-09689-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["9689"],"URL":"https:\/\/doi.org\/10.1186\/s12885-022-09689-9","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,13]]},"assertion":[{"value":"14 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study will be conducted according to the principles of the declaration of Helsinki (Fortaleza, Brazil, October 2013), in accordance with the Medical Research Involving Human Subjects Act and in accordance with Good Clinical Practice standards. The study protocol has been approved by the ethics committee of all patient recruiting centers: the ethics committee of University Clinical Hospital of Valencia, Spain (reference number 2018\/205), the institutional review board of VU University Medical Center Amsterdam (reference number 2019.355. NL 69480.02919), the ethics committee of Instituto de Previsi\u00f3n Social, Asuncion-Paraguay (reference number CA N\u00b011-020\/19), the ethical research committee of Instituto Alexander Fleming, Buenos Aires Argentina (Resolution July 25th, 2019, for LEGACy study 1 and 2 and October 3rd, 2019 for LEGACy study 3); the ethical committee of Instituto Nacional de Cancerologia (INCAN, M\u00e9xico (reference number INCAN\/CEI\/0486\/19). The ethics committee of the University Center of Sao Joao and Medicine Faculty of Porto University, Portugal, reference 100\/019, the scientific ethical Committee Pontificia University of Chili, reference 180806007, and the Drug research ethics committee of Vall d\u2019Hebron University Hospital, Barcelona, Spain with references PR (AG)387\/2019 approved on October 29th, 2019 for LEGACy study 1, PR (AG)388\/2019 approved in December 13th 2019 for LEGACy study 2 and PR (AG)419\/2019 approved in January 30th, 2020 for Legacy study 3 respectively. In case of important protocol modifications, the Principal Coordinating Investigator will inform the Principal Investigators of all study sites. They will then forward the amendments to the associated ethics committees and trial participants. All participants provide written informed consent before study enrolment. Each data-contributing partner shall undergo online ethical and data training before the start of data collection and will manage access to the data of their center through this security system. Inside this system, a patient ID generator will generate a unique code for each participating patient to maintain data privacy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"646"}}