Genetic polymorphisms in carcinogen metabolism and their association to hereditary nonpolyposis colon cancer.
Genetic polymorphisms in carcinogen metabolism and their association to hereditary nonpolyposis colon cancer.
复制标题
致癌物代谢的遗传多态性及其与遗传性非息肉性结肠癌的关联。
DOI：
10.1016/s0016-5085(98)70017-4
复制
发表时间：
1998
期刊：
影响因子：
29.4
通讯作者：
Peltomäki,P
中科院分区：
文献类型：
--
作者：
Moisio,AL;Sistonen,P;Mecklin,JP;Järvinen,H;Peltomäki,P
Background & AimsThe phenotype of hereditary nonpolyposis colorectal cancer shows interfamilial and intrafamilial variation even in the presence of identical predisposing mutations, suggesting the existence of additional phenotype determinants. The modifying role of genetic polymorphisms in loci involved in carcinogen metabolism was studied.MethodsWe focused on colon cancers from kindreds sharing one of two predisposing mutations (mutation 1 or 2) in the mismatch repair gene MLH1 (78 and 14 tumors, respectively). Polymorphisms in N-acetyltransferase 1 (NAT1) and glutathione S-transferase (GST) M1 and GSTT1 were investigated.ResultsThe NAT1 allele 10 was associated with lower median age at diagnosis in both groups. In mutation 1 group, the NAT1 allele 10 was a risk factor for distal tumor location, both alone (P = 0.028) and combined with the GSTT1-positive genotype (P = 0.008). On the other hand, the combined null genotype of GSTM1 and GSTT1 was associated with proximal tumors. Associations with tumor location were not observed in patients with mutation 2, probably reflecting a small sample size.ConclusionsThe results suggest that genetic polymorphisms in carcinogen metabolism modify the age of onset and tumor location in individuals with inherited deficiency of DNA mismatch repair. GASTROENTEROLOGY 1998;115:1387-1394
