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While overall global gastric cancer incidence declines, rising burden among individuals under 40 years has made YOGC a distinct entity with unique drivers and unmet needs. 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As a result, treatments frequently mirror approaches designed for older patients.","Answer","https://schema.org",{"og:url":83,"og:type":116,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":118,"canonical":83},"index,follow",{"doc_id":120,"site_id":62},353518,1790171511,{"code":4,"msg":5,"data":123},{"doc_id":120,"user_id":124,"nickname":92,"user_avatar":125,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":131,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":132,"faqs":133,"seo_title":134,"seo_description":67,"update_tm":135,"read_time":136},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","J Gastric Cancer. 2026 Jan;26(1):52-61 [https://doi.org/10.5230/jgc.2026.26.e9](https://doi.org/10.5230/jgc.2026.26.e9)[ ](https://doi.org/10.5230/jgc.2026.26.e9)pISSN 2093-582X·eISSN 2093-5641  \nReview Article  \nReceived: Dec 2, 2025  \nRevised: Dec 8, 2025  \nAccepted: Dec 9, 2025  \nPublished online: Dec 30, 2025  \nCorrespondence to  \nAnwaar Saeed  \nDivision of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center (UPMC) and UPMC Hillman Cancer Center, 5115 Centre Ave, Pittsburgh, PA 15232, USA.  \nEmail: [saeeda3@upmc.edu](saeeda3@upmc.edu)  \nCopyright © 2026. Korean Gastric Cancer Association  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0](creativecommons.org/licenses/by-nc/4.0)) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nORCID iDs  \nIsabella Michelon  [https://orcid.org/0000-0002-7062-0403](https://orcid.org/0000-0002-7062-0403)[ ](https://orcid.org/0000-0002-7062-0403)Anwaar Saeed  [https://orcid.org/0000-0001-8024-9401](https://orcid.org/0000-0001-8024-9401)  \nConflict of Interest  \nThe author M. I. declares no conflicts of interest. S.A. reports consulting or advisory board roles with AstraZeneca, Bristol-Myers Squibb, Merck, Exelixis, Pfizer, Xilio therapeutics, Taiho, Amgen, Autem therapeutics, Arcus therapeutics, KAHR Medical, and Daiichi Sankyo, as  \nYoung-Onset Gastric Cancer: Clinical and Genetic Perspectives  \nIsabella Michelon  1,2, Anwaar Saeed  3  \n1Department of Medicine, Catholic University of Pelotas, Pelotas, Brazil  \n2Division of Hematology and Oncology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA, USA  \n3Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh Medical Center (UPMC) and UPMC Hillman Cancer Center, Pittsburgh, PA, USA  \nABSTRACT  \nYoung-onset gastric cancer (YOGC) is an increasingly recognized subtype that challenges traditional assumptions about gastric cancer (GC) biology. Although the overall global incidence of GC continues to decline, the rising burden among individuals aged  \n\u003C40 years has reshaped clinical perceptions, highlighting YOGC as a distinct entity with unique drivers and unmet needs. It is frequently associated with diffuse-type histology and enrichment of genomically stable or microsatellite stable/epithelial–mesenchymal transition molecular subtypes, diverging from conventional late-onset diseases. Family history remains the strongest risk factor; however, most cases are sporadic, suggesting amultifactorial interplay between inherited susceptibility, environmental exposure, and earlylife carcinogenic pathways. YOGC is also associated with a unique genetic and molecular profile with predominance of CDH1, RHOA, and CLDN18–ARHGAP alterations, aligned with low human epidermal growth factor 2 expression. Clinically, nonspecific symptoms and lack of screening recommendations often result in diagnosis at advanced stages. Thus, current treatment approaches largely mirror those designed for older patients. This review synthesizes evolving knowledge on the epidemiology, molecular and genetic landscape, and clinical behavior of YOGC. We emphasize opportunities to refine risk stratification, integrate hereditary cancer management, and adopt emerging tools, such as liquid biopsy, for early detection and disease monitoring. Ultimately, defining the biological foundations of YOGC may enable tailored interventions and improve prognosis in this increasingly relevant and understudied population.  \nKeywords: Stomach neoplasms; Gastric cancer; Young adult  \nINTRODUCTION  \nGastric cancer (GC) is the fifth most common cancer worldwide, affecting over one million individuals and culminating in 770,000 deaths by 2020 [1]. Eastern and Western Asia, Eastern Europe, and","cbCaidEJvn8kZ5SC","https://ap.wps.com/l/cbCaidEJvn8kZ5SC","pdf",796270,"English","# Abstract\n# Introduction\n## Global burden and epidemiology\n## Risk factors and molecular subtypes\n## Clinical challenges and treatment implications","[{\"question\":\"Why are YOGC diagnoses often made at advanced stages?\",\"answer\":\"Nonspecific symptoms and the lack of screening recommendations contribute to diagnosis at later stages. As a result, treatments frequently mirror approaches designed for older patients.\"}]","Young-Onset Gastric Cancer - Clinical and Genetic Perspectives | PDF",1790105885,25]