{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:02:33Z","timestamp":1785402153714,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia"},{"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011776","name":"Portuguese Institute of Oncology of Porto","doi-asserted-by":"publisher","award":["PI127-CI-IPOP-118-2019"],"award-info":[{"award-number":["PI127-CI-IPOP-118-2019"]}],"id":[{"id":"10.13039\/501100011776","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PI127-CI-IPOP-118-2019"],"award-info":[{"award-number":["PI127-CI-IPOP-118-2019"]}],"id":[{"id":"https:\/\/ror.org\/027ras364","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024791","name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences","doi-asserted-by":"crossref","award":["UIDB\/04033\/2025"],"award-info":[{"award-number":["UIDB\/04033\/2025"]}],"id":[{"id":"10.13039\/501100024791","id-type":"DOI","asserted-by":"crossref"}]},{"award":["UIDB\/04033\/2025"],"award-info":[{"award-number":["UIDB\/04033\/2025"]}],"id":[{"id":"https:\/\/ror.org\/01h1p3y81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production","award":["LA\/P\/0126\/2020"],"award-info":[{"award-number":["LA\/P\/0126\/2020"]}]},{"name":"Portuguese League Against Cancer\u2014Northern Branch"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Cancer-associated cachexia (CAC) is a multifactorial syndrome driven by a profound metabolic and inflammatory dysregulation. Due to the central role of the insulin-like growth factor 1 (IGF-1) pathway in regulating muscle mass, energy metabolism, and inflammation, this study evaluated the relevance of five IGF-1 axis-related single-nucleotide polymorphisms (SNPs), namely IGF1 rs6220, insulin-like growth factor 1 receptor (IGF1R) rs2016347 and rs2684788, growth hormone receptor (GHR) rs6873545, and insulin receptor substrate 1 (IRS1) rs1801278. Methods: The impact of these variants on CAC onset and overall survival (OS) was assessed in a cohort of 140 cancer patients. Results: While overall-cohort analyses did not reach statistical significance, exploratory analyses suggested potential associations between the IGF1 rs6220 GG and GHR rs6873545 CC genotypes and increased CAC risk in male patients. A trend for higher CAC prevalence was also noted in younger patients (&lt;63 years) with the rs6873545 CC genotype. For pre-CAC and CAC patients, exploratory subgroup analyses on patients\u2019 OS were conducted following no significant results in the overall cohort. Among older patients and those with high prognostic nutritional index (PNI; &gt;44.2), the IGF1 rs6220 G allele was associated with longer OS. Conversely, the IGF1R rs2016347 G allele and rs2684788 T allele were linked to poorer OS across multiple pre-CAC and CAC subgroups. The effects of GHR rs6873545 varied across subgroups, suggesting context-dependent activity. Conclusions: This study highlights the functional heterogeneity of IGF-1 axis-related genetic variants, indicating potential to serve as predictors of CAC. Given the exploratory nature of these findings, validation in larger cohorts is required to confirm the associations found.<\/jats:p>","DOI":"10.3390\/cancers18111822","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:25:31Z","timestamp":1780399531000},"page":"1822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variability in the IGF-1 Axis Modulates Cancer-Associated Cachexia and Prognosis"],"prefix":"10.3390","volume":"18","author":[{"given":"Mariana","family":"Moreira Pires","sequence":"first","affiliation":[{"name":"Faculty of Medicine (FMUP), University of Porto, 4200-072 Porto, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas","family":"Guerra de Melo","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1969-9363","authenticated-orcid":false,"given":"Ana Carolina Le\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (FMUP), University of Porto, 4200-072 Porto, Portugal"},{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virg\u00ednia","family":"Rocha Dias","sequence":"additional","affiliation":[{"name":"Day Hospital, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia","family":"Silva","sequence":"additional","affiliation":[{"name":"Day Hospital, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paula","family":"Silva","sequence":"additional","affiliation":[{"name":"Palliative Care Service, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-524X","authenticated-orcid":false,"given":"Joana","family":"M. 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Santos","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-9770","authenticated-orcid":false,"given":"Tiago","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"},{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3680-7757","authenticated-orcid":false,"given":"Val\u00e9ria","family":"Tavares","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (EMCB), Fernando Pessoa University, 4420-096 Gondomar, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)\/Department of Pathology and Laboratory Medicine\/RISE\u2014Associate Laboratory (Health Research Network)\/Porto Comprehensive Cancer Centre Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal"},{"name":"School of Medicine and Biomedical Sciences (EMCB), Fernando Pessoa University, 4420-096 Gondomar, Portugal"},{"name":"Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"European Cancer Organisation (ECO), 1040 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.gendis.2022.03.002","article-title":"Drugging IGF-1R in cancer: New insights and emerging opportunities","volume":"10","author":"Wang","year":"2023","journal-title":"Genes Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s11010-024-05041-w","article-title":"The prowess of metabolomics in cancer research: Current trends, challenges and future perspectives","volume":"480","author":"Taunk","year":"2024","journal-title":"Mol. 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