Talseth Bente A, Meldrum Cliff, Suchy Janina, Kurzawski Grzegroz, Lubinski Jan, Scott Rodney J
Discipline of Medical Genetic, Faculty of Health, University of Newcastle and the Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2307-10. doi: 10.1158/1055-9965.EPI-06-0040.
Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with germ-line mutations in DNA mismatch repair genes. There is considerable variation in disease expression that cannot be explained by genotype/phenotype correlation, which is likely to be the result of polymorphic modifier genes. One candidate group of modifiers is the xenobiotic clearance enzyme genes that encode CYP1A1, GSTM1, GSTT1, GSTP1, and NAT2. Alterations in these xenobiotic clearance genes can potentially influence the host response to carcinogen exposure and thereby alter cancer risk. We have investigated eight polymorphisms in xenobiotic clearance genes to assess the effect on the risk of disease in mutation positive HNPCC patients.
DNA samples from 220 mutation-positive HNPCC participants (86 Australian and 134 Polish) were genotyped for single nucleotide polymorphisms (SNP) in CYP1A1, GSTM1, GSTT1, GSTP1, and NAT2. The association between the SNPs and disease characteristics, disease expression and age of diagnosis of colorectal cancer (CRC), was tested with Pearson's chi(2) and Kaplan-Meier survival analysis.
The HNPCC population displays a significant difference in the genotype frequency distribution between CRC patients and unaffected mismatch repair gene mutation carriers for the CYP1A1 SNP where the CRC patients harbor more of the mutant genotype.
Evidence from this study is not conclusive, but our data suggest that the CYP1A1 influences disease expression in individuals with HNPCC.
遗传性非息肉病性结直肠癌（HNPCC）与DNA错配修复基因的种系突变相关。疾病表现存在相当大的差异，无法通过基因型/表型相关性来解释，这可能是多态性修饰基因作用的结果。一组候选修饰基因是编码CYP1A1、GSTM1、GSTT1、GSTP1和NAT2的外源性物质清除酶基因。这些外源性物质清除基因的改变可能会影响宿主对致癌物暴露的反应，从而改变癌症风险。我们研究了外源性物质清除基因中的8种多态性，以评估其对突变阳性HNPCC患者疾病风险的影响。
对220名突变阳性HNPCC参与者（86名澳大利亚人和134名波兰人）的DNA样本进行CYP1A1、GSTM1、GSTT1、GSTP1和NAT2单核苷酸多态性（SNP）基因分型。采用Pearson卡方检验和Kaplan-Meier生存分析，检测SNP与疾病特征、疾病表现以及结直肠癌（CRC）诊断年龄之间的关联。
在CYP1A1 SNP方面，HNPCC人群中CRC患者与未受影响的错配修复基因突变携带者之间的基因型频率分布存在显著差异，CRC患者携带更多的突变基因型。
本研究的证据尚无定论，但我们的数据表明CYP1A1会影响HNPCC个体的疾病表现。
