Faculty of Health and Medical Sciences, University of Copenhagen, Nørregade 10, 1165, Copenhagen, Denmark.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Denmark.
Fam Cancer. 2022 Oct;21(4):453-462. doi: 10.1007/s10689-022-00291-3. Epub 2022 Mar 16.
Germline biallelic pathogenic variants (PVs) in NTHL1 have since 2015 been associated with the autosomal recessive tumor predisposition syndrome: NTHL1 tumor syndrome or NTHL1-associated polyposis. In this systematic review, we aim to systematically investigate the phenotypic and genotypic spectrum of the condition including occurrence of both benign and malignant tumors. The databases PubMed, EMBASE, and Scopus were searched. The search was conducted the 25th of august 2021. We included patients with germline PVs, both heterozygous and homo-/compound heterozygous carriers. Twenty-one papers were selected including 47 patients with biallelic PVs in NTHL1 in 32 families. Twenty-three out of 47 patients (49%) were diagnosed with colorectal cancer (CRC) (mean age: 55, range: 31-73) and 12 out of 22 female patients (55%) were diagnosed with breast cancer (mean age: 49, range: 36-63). Apart from three, all patients who underwent a colonoscopy, had colonic adenomas (93%), and three patients (6%) had duodenal adenomatosis. We also identified 158 heterozygous carriers of germline PVs in NTHL1. Twenty-six out of 68 (38%) heterozygous carriers, who underwent colonoscopy, had colonic polyps or adenomas. Twenty-nine heterozygous carriers (18%) were diagnosed with CRC and 59 (49%) with breast cancer. We observed a high frequency of early onset CRC and breast cancer in patients with NTHL1 tumor syndrome. Subsequently, colorectal, breast, and endometrial cancer screening programs are recommended for NTHL1 biallelic carriers. Trial registry PROSPERO: CRD42021275159.
自 2015 年以来，NTHL1 中的种系双等位致病性变异（PV）与常染色体隐性肿瘤易感性综合征相关：NTHL1 肿瘤综合征或 NTHL1 相关息肉病。在这项系统评价中，我们旨在系统地研究该疾病的表型和基因型谱，包括良性和恶性肿瘤的发生。检索了 PubMed、EMBASE 和 Scopus 数据库。搜索于 2021 年 8 月 25 日进行。我们纳入了种系 PV 患者，包括杂合子和纯合子/复合杂合子携带者。选择了 21 篇论文，其中包括 32 个家庭的 47 名 NTHL1 种系双等位 PV 患者。47 名患者中有 23 名（49%）被诊断为结直肠癌（CRC）（平均年龄：55 岁，范围：31-73 岁），22 名女性患者中有 12 名（55%）被诊断为乳腺癌（平均年龄：49 岁，范围：36-63 岁）。除了 3 名患者外，所有接受结肠镜检查的患者均有结肠腺瘤（93%），3 名患者（6%）有十二指肠腺瘤病。我们还在 NTHL1 中鉴定了 158 名种系 PV 的杂合子携带者。68 名接受结肠镜检查的杂合子携带者中有 26 名（38%）有结肠息肉或腺瘤。29 名杂合子携带者（18%）被诊断为 CRC，59 名（49%）被诊断为乳腺癌。我们观察到 NTHL1 肿瘤综合征患者 CRC 和乳腺癌的发病年龄较早。因此，建议对 NTHL1 双等位基因携带者进行结直肠癌、乳腺癌和子宫内膜癌的筛查计划。试验注册 PROSPERO：CRD42021275159。
