Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition

BMC Cancer. 2006 Oct 9;6:243. doi: 10.1186/1471-2407-6-243.


Background: The observation that germline mutations in the oxidative DNA damage repair gene MUTYH cause colorectal cancer (CRC) provides strong evidence that dysregulation of the base excision repair (BER) pathway influences disease susceptibility. It is conceivable that germline sequence variation in other BER pathway genes such as NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 also contribute to CRC susceptibility.

Methods: To evaluate whether sequence variants of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC susceptibility alleles, we screened the coding sequence and intron-exon boundaries of these genes in 94 familial CRC cases in which involvement of known genes had been excluded.

Results: Three novel missense variants were identified NEIL2 C367A, TDG3 A196G and UNG2 C262T in patients, which were not observed in 188 healthy control DNAs.

Conclusion: We detected novel germline alterations in NEIL2, TDG and UNG patients with CRC. The results suggest a limited role for NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 in development of CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 5' Untranslated Regions / genetics
  • Adenocarcinoma / genetics*
  • Aged
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms / genetics*
  • DNA Glycosylases / genetics
  • DNA Mutational Analysis
  • DNA Repair / genetics*
  • DNA, Neoplasm / genetics*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics
  • Deoxyribonuclease (Pyrimidine Dimer) / genetics
  • Female
  • Frameshift Mutation
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Mutation, Missense
  • Neoplasm Proteins / genetics
  • Point Mutation
  • Polymerase Chain Reaction
  • Rectal Neoplasms / genetics
  • Thymine DNA Glycosylase / genetics
  • Uracil-DNA Glycosidase / genetics


  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Deoxyribonuclease (Pyrimidine Dimer)
  • NTHL1 protein, human
  • DNA Glycosylases
  • NEIL1 protein, human
  • SMUG1 protein, human
  • Thymine DNA Glycosylase
  • Uracil-DNA Glycosidase
  • DNA-3-methyladenine glycosidase II
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • NEIL2 protein, human