Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context
Summary: Background: Li-Fraumeni Syndrome (LFS) is a predisposition associated with early onset malignant tumors caused by germline pathogenic variants in the TP53 gene. Although rare worldwide, LFS is prevalent in Southern Brazil due to the founder pathogenic variant R337H. Here, we assessed tumor...
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Elsevier
2025-02-01
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| Series: | The Lancet Regional Health. Americas |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667193X24003090 |
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| author | Pedro A.F. Galante Gabriela D.A. Guardia Janina Pisani Renata L. Sandoval Mateus C. Barros-Filho Ana Carolina Leite Vieira Costa Gifoni Diogo F.C. Patrão Patricia Ashton-Prolla Vitor Fiorin de Vasconcellos Claire Freycon Arnold Levine Pierre Hainaut Maria Isabel Achatz |
| author_facet | Pedro A.F. Galante Gabriela D.A. Guardia Janina Pisani Renata L. Sandoval Mateus C. Barros-Filho Ana Carolina Leite Vieira Costa Gifoni Diogo F.C. Patrão Patricia Ashton-Prolla Vitor Fiorin de Vasconcellos Claire Freycon Arnold Levine Pierre Hainaut Maria Isabel Achatz |
| author_sort | Pedro A.F. Galante |
| collection | DOAJ |
| description | Summary: Background: Li-Fraumeni Syndrome (LFS) is a predisposition associated with early onset malignant tumors caused by germline pathogenic variants in the TP53 gene. Although rare worldwide, LFS is prevalent in Southern Brazil due to the founder pathogenic variant R337H. Here, we assessed tumor patterns and temporal trends, cancer risk, and sex differences of adult R337H carriers and carriers of other LFS-associated variants. Methods: We retrospectively analyzed 708 adults, combining data from two sources: the Brazilian Li-Fraumeni Syndrome Study cohort and the NCI TP53 database. We assessed the clinical characteristics of 303 adults with R337H and compared them with those associated with 405 carriers of other TP53 variants. Findings: R337H carriers, compared to adult carriers of other TP53 variants typical of LFS, had a lower cumulative risk of developing cancer (54% vs 78%). Female R337H carriers were at a higher risk than males (65% vs 30%) and had a higher risk of developing a second primary cancer, underscoring a strong sex bias not observed in carriers of other variants. The most common cancers were breast cancer and soft tissue sarcoma in females, and soft tissue sarcoma and prostate cancer in males. Common second malignancies were breast cancer in females and lung cancer in males. Interpretation: This study shows that R337H is associated with a lifetime risk of multiple LFS-spectrum cancers but with incomplete penetrance, particularly in males. Our findings suggest that R337H carriers would benefit from tailored surveillance and risk reduction strategies. Funding: São Paulo Research Foundation, Conselho Nacional de Pesquisa, and Hospital Sírio-Libanês. |
| format | Article |
| id | doaj-art-72a563bf47494409b8574f9b7969b217 |
| institution | Kabale University |
| issn | 2667-193X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Regional Health. Americas |
| spelling | doaj-art-72a563bf47494409b8574f9b7969b2172025-01-19T06:26:52ZengElsevierThe Lancet Regional Health. Americas2667-193X2025-02-0142100982Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in contextPedro A.F. Galante0Gabriela D.A. Guardia1Janina Pisani2Renata L. Sandoval3Mateus C. Barros-Filho4Ana Carolina Leite Vieira Costa Gifoni5Diogo F.C. Patrão6Patricia Ashton-Prolla7Vitor Fiorin de Vasconcellos8Claire Freycon9Arnold Levine10Pierre Hainaut11Maria Isabel Achatz12Centro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo, Brazil; Corresponding author.Centro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, BrazilDepartment of Oncology, Hospital Sírio-Libanês, Brasília, BrazilCentro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo, BrazilOncologia D'Or, Fortaleza, BrazilHospital Israelita Albert Einstein, São Paulo, BrazilServiço de Genética Médica, Hospital de Clínicas de Porto Alegre, BrazilHospital Universitário Cassiano Antonio de Moraes HUCAM-EBSERH, Espírito Santo, BrazilUniversity Grenoble Alpes, Inserm 1209 CNRS 5309, Institute for Advanced Biosciences, Grenoble, FranceInstitute for Advanced Study, Princeton, New Jersey, USAUniversity Grenoble Alpes, Inserm 1209 CNRS 5309, Institute for Advanced Biosciences, Grenoble, FranceDepartment of Oncology, Hospital Sírio-Libanês, São Paulo, Brazil; Corresponding author.Summary: Background: Li-Fraumeni Syndrome (LFS) is a predisposition associated with early onset malignant tumors caused by germline pathogenic variants in the TP53 gene. Although rare worldwide, LFS is prevalent in Southern Brazil due to the founder pathogenic variant R337H. Here, we assessed tumor patterns and temporal trends, cancer risk, and sex differences of adult R337H carriers and carriers of other LFS-associated variants. Methods: We retrospectively analyzed 708 adults, combining data from two sources: the Brazilian Li-Fraumeni Syndrome Study cohort and the NCI TP53 database. We assessed the clinical characteristics of 303 adults with R337H and compared them with those associated with 405 carriers of other TP53 variants. Findings: R337H carriers, compared to adult carriers of other TP53 variants typical of LFS, had a lower cumulative risk of developing cancer (54% vs 78%). Female R337H carriers were at a higher risk than males (65% vs 30%) and had a higher risk of developing a second primary cancer, underscoring a strong sex bias not observed in carriers of other variants. The most common cancers were breast cancer and soft tissue sarcoma in females, and soft tissue sarcoma and prostate cancer in males. Common second malignancies were breast cancer in females and lung cancer in males. Interpretation: This study shows that R337H is associated with a lifetime risk of multiple LFS-spectrum cancers but with incomplete penetrance, particularly in males. Our findings suggest that R337H carriers would benefit from tailored surveillance and risk reduction strategies. Funding: São Paulo Research Foundation, Conselho Nacional de Pesquisa, and Hospital Sírio-Libanês.http://www.sciencedirect.com/science/article/pii/S2667193X24003090Li-Fraumeni syndromeR337H variantTP53Germline |
| spellingShingle | Pedro A.F. Galante Gabriela D.A. Guardia Janina Pisani Renata L. Sandoval Mateus C. Barros-Filho Ana Carolina Leite Vieira Costa Gifoni Diogo F.C. Patrão Patricia Ashton-Prolla Vitor Fiorin de Vasconcellos Claire Freycon Arnold Levine Pierre Hainaut Maria Isabel Achatz Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context The Lancet Regional Health. Americas Li-Fraumeni syndrome R337H variant TP53 Germline |
| title | Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context |
| title_full | Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context |
| title_fullStr | Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context |
| title_full_unstemmed | Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context |
| title_short | Personalized screening strategies for TP53 R337H carriers: a retrospective cohort study of tumor spectrum in Li-Fraumeni syndrome adult carriersResearch in context |
| title_sort | personalized screening strategies for tp53 r337h carriers a retrospective cohort study of tumor spectrum in li fraumeni syndrome adult carriersresearch in context |
| topic | Li-Fraumeni syndrome R337H variant TP53 Germline |
| url | http://www.sciencedirect.com/science/article/pii/S2667193X24003090 |
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