{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:21:04Z","timestamp":1781716864249,"version":"3.54.5"},"reference-count":9,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,4,2]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>NTHL1-associated tumour syndrome, linked to germline variants in the NTHL1 gene, is a rare colorectal cancer (CRC) syndrome. Initially identified in CRC cases, recent literature expanded its association to various malignancies, including breast, bladder and endometrial cancers. We present the case of a premenopausal woman with a history of left breast invasive carcinoma, treated with mastectomy, chemotherapy, radiation and endocrine therapy. Two years later, she developed new-onset dyspnoea, and further evaluation revealed a pleural effusion with pathology consistent with colonic adenocarcinoma. No primary lesions were identified on oesophagogastroduodenoscopy or colonoscopy. Genetic testing revealed an NTHL1 heterozygous variant. She was started on first-line therapy for metastatic CRC with capecitabine, oxaliplatin and bevacizumab. This case contributes to the evolving understanding of NTHL1-associated tumour syndrome, emphasising the importance of genetic evaluation in patients with multiple malignancies and the need for further research into the role of NTHL1 variants in cancer risk.<\/jats:p>","DOI":"10.1136\/bcr-2024-261111","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:25:08Z","timestamp":1746055508000},"page":"e261111","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Heterozygous NTHL1 variant in a breast cancer survivor with malignant pleural effusion revealing metastatic colon adenocarcinoma"],"prefix":"10.1136","volume":"18","author":[{"given":"Lauren K","family":"Lewis","sequence":"first","affiliation":[{"name":"Internal Medicine, Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian M","family":"Varda","sequence":"additional","affiliation":[{"name":"Hematology Oncology, Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E","family":"McCann","sequence":"additional","affiliation":[{"name":"Hematology Oncology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7997-2835","authenticated-orcid":false,"given":"Charity","family":"Huang","sequence":"additional","affiliation":[{"name":"Hematology Oncology, Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025082722312201000_18.4.e261111.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2020.102920"},{"key":"2025082722312201000_18.4.e261111.2","doi-asserted-by":"crossref","first-page":"21127","DOI":"10.1038\/s41598-023-47441-w","article-title":"NTHL1 is a recessive cancer susceptibility gene","volume":"13","author":"Nurmi","year":"2023","journal-title":"Sci Rep"},{"key":"2025082722312201000_18.4.e261111.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.12.011"},{"key":"2025082722312201000_18.4.e261111.4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41523-021-00255-3","article-title":"Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects","volume":"7","author":"Li","year":"2021","journal-title":"NPJ Breast Cancer"},{"key":"2025082722312201000_18.4.e261111.5","unstructured":"National center for biotechnology information. ClinVar. N.d Available: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV001074525.6\/"},{"key":"2025082722312201000_18.4.e261111.6","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1053\/j.gastro.2020.08.042","article-title":"Monoallelic NTHL1 Loss-of-Function Variants and Risk of Polyposis and Colorectal Cancer","volume":"159","author":"Elsayed","year":"2020","journal-title":"Gastroenterology"},{"key":"2025082722312201000_18.4.e261111.7","unstructured":"Kuiper RP , Nielsen M , Voer RM , et al . NTHL1 tumor syndrome. In: Adam MP , Feldman J , Mirzaa GM , eds. GeneReviews. 1993: 32239880."},{"key":"2025082722312201000_18.4.e261111.8","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.3390\/genes14051025","article-title":"Hereditary Cancer Syndromes: A Comprehensive Review with a Visual Tool","volume":"14","author":"Garutti","year":"2023","journal-title":"Genes (Basel)"},{"key":"2025082722312201000_18.4.e261111.9","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-022-00291-3"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2024-261111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T05:31:35Z","timestamp":1756359095000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2024-261111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":9,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,30]]},"published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1136\/bcr-2024-261111"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2024-261111","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]}}}