Intestinal and extraintestinal neoplasms in patients with NTHL1 tumor syndrome: a systematic review

1 Citation (Scopus)


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.

Original languageEnglish
JournalFamilial Cancer
Issue number4
Pages (from-to)453-462
Number of pages10
Publication statusPublished - 21 Oct 2022


  • Breast cancer
  • Colorectal cancer
  • Extraintestinal neoplasms
  • Intestinal neoplasms
  • NTHL1 tumor syndrome
  • NTHL1-associated polyposis
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Colorectal Neoplasms/genetics
  • Male
  • Adenoma
  • Breast Neoplasms
  • Deoxyribonuclease (Pyrimidine Dimer)
  • Germ-Line Mutation
  • Adenomatous Polyposis Coli/diagnosis
  • Adult
  • Female
  • Aged


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