{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:16:50Z","timestamp":1779308210557,"version":"3.51.4"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Glob Oncol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>To characterize tumor-site distribution, age at diagnosis, sex distribution, and tumor multiplicity in a Brazilian institutional Lynch syndrome (LS) cohort stratified by mismatch repair (MMR) gene and genetic testing status, and to assess the impact of including nontested (NT) relatives.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective, registry-based family cohort study of families ascertained in 2013-2019 with pathogenic or likely pathogenic variants in\n                      <jats:italic toggle=\"yes\">MLH1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MSH2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">MSH6<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">PMS2<\/jats:italic>\n                      , or\n                      <jats:italic toggle=\"yes\">EPCAM<\/jats:italic>\n                      . For each proband, pedigree enumeration was limited to one cancer-enriched parental lineage. Adults (\u226518 years) were included for tumor-site analyses. Relatives were classified as carriers (genotype-confirmed), noncarriers, or NT. Only primary malignant tumors were counted. Outcomes were any primary malignancy, multiplicity (\u22652 primaries), age at first primary, and gene-specific tumor profiles summarized per person and per tumor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Forty-seven families comprised 729 relatives; 111 (15.2%) underwent testing, identifying 78 carriers. Cohort composition was 78 (10.7%) carriers, 33 (4.5%) noncarriers, and 618 (84.8%) NT. Carriers were more often affected (\u22651 tumor: 64.1%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      37.9% NT\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      18.2% noncarriers), younger at first cancer (mean 42.3\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      47.3 years in NT), and more likely to have multiple primaries. Colorectal cancer predominated across genes; endometrial tumors were more frequent in\n                      <jats:italic toggle=\"yes\">MLH1\/MSH2<\/jats:italic>\n                      , and urothelial tumors clustered in\n                      <jats:italic toggle=\"yes\">MSH2<\/jats:italic>\n                      (descriptive). After false discovery rate control across LS-spectrum sites, site-wise multigene contrasts were not significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Carriers showed earlier onset and higher multiplicity, with gene-linked patterns consistent with LS heterogeneity. Low testing uptake broadened observed spectra among NT relatives, supporting cascade testing and genotype-tailored surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/go-25-00708","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:59:07Z","timestamp":1779307147000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Cancer Spectrum and Gene-Specific Patterns in Lynch Syndrome: Insights From 47 Families in a Brazilian Institutional Cohort"],"prefix":"10.1200","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8231-2769","authenticated-orcid":true,"given":"Thiago","family":"Bassaneze","sequence":"first","affiliation":[{"name":"PhD Program in Oncology, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-2578","authenticated-orcid":true,"given":"F\u00e1bio","family":"Oliveira Ferreira","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"},{"name":"Genomic Medicine Service, Benefic\u00eancia Portuguesa de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8446-3675","authenticated-orcid":true,"given":"Renata Lazari","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Department of Oncogenetics, Hospital S\u00edrio-Liban\u00eas, Bras\u00edlia, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina Pontes","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Oncogenetics, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6673-5665","authenticated-orcid":true,"given":"Carla","family":"Vanessa Quirino","sequence":"additional","affiliation":[{"name":"Department of Oncogenetics, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-567X","authenticated-orcid":false,"given":"Pablo Domingos","family":"Rodrigues de Nicola","sequence":"additional","affiliation":[{"name":"Genomic Medicine Service, Benefic\u00eancia Portuguesa de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Isabel","family":"Achatz","sequence":"additional","affiliation":[{"name":"Department of Oncogenetics, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mev","family":"Dominguez-Valentin","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedito Mauro","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3878"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_208341"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.283"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13053-023-00263-3"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101909"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1316"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2021.02.003"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3599-4"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.07.017"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:FAME.0000026810.99776.e9"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-010-9373-2"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139753"},{"key":"e_1_3_6_14_2","first-page":"18","article-title":"The germline mutational landscape of Brazilian patients with hereditary cancer syndromes","volume":"41","author":"Palmero EI","year":"2018","unstructured":"Palmero EI, Carraro DM, Alemar B, et al: The germline mutational landscape of Brazilian patients with hereditary cancer syndromes. Genet Mol Biol 41:18-29, 2018","journal-title":"Genet Mol Biol"},{"key":"e_1_3_6_15_2","first-page":"15","article-title":"Spectrum of germline variants in Brazilian Lynch syndrome families and clinical correlations","volume":"17","author":"Campacci N","year":"2019","unstructured":"Campacci N, Louren\u00e7o JJ, Asprino PF, et al: Spectrum of germline variants in Brazilian Lynch syndrome families and clinical correlations. Hered Cancer Clin Pract 17:15, 2019","journal-title":"Hered Cancer Clin Pract"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70510-X"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh034"},{"key":"e_1_3_6_18_2","unstructured":"National Comprehensive Cancer Network: Genetic\/Familial High-Risk Assessment: Colorectal Endometrial and Gastric. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae). Version 2.2024. 2024"},{"key":"e_1_3_6_19_2","first-page":"1","article-title":"Variants database","volume":"16","author":"International Society for Gastrointestinal Hereditary Tumours (InSiGHT)","year":"2017","unstructured":"International Society for Gastrointestinal Hereditary Tumours (InSiGHT): Variants database. Fam Cancer 16:1-134, 2017","journal-title":"Fam Cancer"},{"key":"e_1_3_6_20_2","volume-title":"International Society for Gastrointestinal Hereditary Tumours","author":"InSiGHT","year":"2005","unstructured":"InSiGHT: International Society for Gastrointestinal Hereditary Tumours. 2005. http:\/\/insight-database.org\/"},{"key":"e_1_3_6_21_2","first-page":"8.23.1","article-title":"Using ClinVar as a resource to support variant interpretation","volume":"89","author":"Harrison SM","year":"2016","unstructured":"Harrison SM, Riggs ER, Maglott DR, et al: Using ClinVar as a resource to support variant interpretation. Curr Protoc Hum Genet 89:8.23.1-8.23.23, 2016","journal-title":"Curr Protoc Hum Genet"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_6_23_2","first-page":"623","article-title":"Mutation spectrum in South American Lynch syndrome families","volume":"10","author":"Dominguez-Valentin M","year":"2011","unstructured":"Dominguez-Valentin M, da Silva FC, dos Santos EM, et al: Mutation spectrum in South American Lynch syndrome families. Fam Cancer 10:623-630, 2011","journal-title":"Fam Cancer"},{"key":"e_1_3_6_24_2","first-page":"525","article-title":"The germline mutational landscape of Lynch syndrome in Brazil: Characterization of germline variants in patients with colorectal cancer","volume":"57","author":"Palmero EI","year":"2018","unstructured":"Palmero EI, Ashton-Prolla P, Rocha JC, et al: The germline mutational landscape of Lynch syndrome in Brazil: Characterization of germline variants in patients with colorectal cancer. Genes Chromosomes Cancer 57:525-533, 2018","journal-title":"Genes Chromosomes Cancer"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31920"}],"container-title":["JCO Global Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/GO-25-00708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T19:59:11Z","timestamp":1779307151000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/GO-25-00708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1200\/GO-25-00708"],"URL":"https:\/\/doi.org\/10.1200\/go-25-00708","relation":{},"ISSN":["2687-8941"],"issn-type":[{"value":"2687-8941","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-02","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500708"}}