TY - JOUR
T1 - Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG, and SMUG1 genes in familial colorectal cancer predisposition
AU - Broderick, Peter
AU - Bagratuni, Tina
AU - Vijayakrishnan, Jairam
AU - Lubbe, Steven
AU - Chandler, Ian
AU - Houlston, Richard S.
PY - 2006/10/9
Y1 - 2006/10/9
N2 - 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 NTHLI, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC susceptibility alleles, we screened the coding sequence and intronexon 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 A 196G 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.
AB - 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 NTHLI, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC susceptibility alleles, we screened the coding sequence and intronexon 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 A 196G 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.
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U2 - 10.1186/1471-2407-6-243
DO - 10.1186/1471-2407-6-243
M3 - Article
C2 - 17029639
AN - SCOPUS:33750614308
SN - 1471-2407
VL - 6
JO - BMC cancer
JF - BMC cancer
M1 - 243
ER -
