Abstract
While familial adenomatous polyposis accounts for approximately 1% of all colorectal cancer, the genetic cause underlying the development of multiple colonic adenomas remains unsolved in many patients. Adenomatous polyposis syndromes can be divided into: familial adenomatous polyposis, MUTYH-associated polyposis, polymerase proofreading associated polyposis and the recently described NTHL1-associated polyposis (NAP). NAP is characterised by recessive inheritance, attenuated adenomatous polyposis, colonic cancer(s) and possible extracolonic malignancies. To date, 11 cases have been reported as having germline homozygous or compound heterozygous mutations in the base excision repair gene NTHL1. Here we present a further case of a 65-year-old male with a history of adenomatous polyposis and bladder cancer, who has a previously described homozygous nonsense variant in the NTHL1 gene. This case is consistent with the emerging phenotype previously described of multiple colorectal adenomas and at least one primary tumour, adding to the small but growing body of literature about NAP.
References
Shussman N, Wexner SD (2014) Colorectal polyps and polyposis syndromes. Gastroenterol Rep 2(1):1–15
Aretz S (2010) The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes. Dtsch Arztebl Int 107(10):163
Weren RD, Ligtenberg MJ, Kets CM et al (2015) A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet 47(6):668–671
Rivera B, Castellsagué E, Bah I, van Kempen LC, Foulkes WD (2015) Biallelic NTHL1 mutations in a woman with multiple primary tumors. N Engl J Med 373(20):1985–1986
Chubb D, Broderick P, Dobbins SE et al (2016) Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer. Nat Commun 7:11883. https://doi.org/10.1038/ncomms11883
Belhadj S, Mur P, Navarro M et al (2017) Delineating the phenotypic spectrum of the NTHL1-associated polyposis. Clin Gastroenterol Hepatol 15(3):461–462
Church J (2016) Polymerase proofreading associated polyposis, and other new syndromes of hereditary colorectal cancer. In: Intestinal polyposis syndromes. Springer, Cham, pp 61–68
Broderick P, Bagratuni T, Vijayakrishnan J, Lubbe S, Chandler I, Houlston RS (2006) Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition. BMC Cancer 6(1):243
Dallosso AR, Dolwani S, Jones N et al (2008) Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3. Gut 57(9):1252–1255
Khan N, Lipsa A, Arunachal G, Ramadwar M, Sarin R (2017) Novel mutations and phenotypic associations identified through APC, MUTYH, NTHL1, POLD1, POLE gene analysis in Indian familial adenomatous polyposis cohort. Sci Rep 7:2214. https://www.nature.com/articles/s41598-017-02319-6
Acknowledgements
We thank the patient for allowing us to report this case.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Groves, A., Gleeson, M. & Spigelman, A.D. NTHL1-associate polyposis: first Australian case report. Familial Cancer 18, 179–182 (2019). https://doi.org/10.1007/s10689-018-0107-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-018-0107-1