NTHL1、NEIL1、NEIL2、MPG、TDG、UNG和SMUG1基因在家族性结直肠癌易感性中的评估。
Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition.
作者信息
Broderick Peter, Bagratuni Tina, Vijayakrishnan Jairam, Lubbe Steven, Chandler Ian, Houlston Richard S
机构信息
Section of Cancer Genetics, Brookes Lawley Building, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
出版信息
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.
背景
氧化DNA损伤修复基因MUTYH中的种系突变会导致结直肠癌（CRC），这一观察结果有力地证明了碱基切除修复（BER）途径的失调会影响疾病易感性。可以想象，其他BER途径基因（如NTHL1、NEIL1、NEIL2、MPG、TDG、UNG和SMUG1）中的种系序列变异也会导致CRC易感性。
方法
为了评估NTHL1、NEIL1、NEIL2、MPG、TDG、UNG和SMUG1基因的序列变异是否可能作为CRC易感等位基因，我们在94例已排除已知基因参与的家族性CRC病例中筛选了这些基因的编码序列和内含子-外显子边界。
结果
在患者中鉴定出三个新的错义变体，即NEIL2 C367A、TDG3 A196G和UNG2 C262T，在188份健康对照DNA中未观察到。
结论
我们在CRC患者的NEIL2、TDG和UNG中检测到新的种系改变。结果表明NTHL1、NEIL1、NEIL2、MPG、TDG、UNG和SMUG1在CRC发生中的作用有限。
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