食管癌患者O^6-烷基鸟嘌呤-DNA烷基转移酶基因多态性研究

Identification of a novel genetic polymorphism of human O 6 alkylguanine DNA alkyltransferase in patients with esophagus cancer *

目的检测中国食管癌高发区居民和高加索居民ＡＧＴ（Ｏ６ａｌｋｙｌｇｕａｎｉｎｅａｌｋｙｌｔｒａｓｆｅｒａｓｅ）的基因多态改变．方法采用ＰＣＲＳＳＣＰ和ＤＮＡ测序方法对河南食管癌高发区居民和高加索居民的癌组织和非癌组织进行基因多态分析．结果多态变异发生于第５外显子的１４３位密码子，并导致该位点的异亮氨酸（ＡＧＴ）被缬氨酸（ＧＴＣ）取代，且１４３位密码子与１７８位密码子的多态改变有一定联系．对９０例中国食管癌高发区居民的食管癌患者的检测发现，２例（２％）存在１４３／１７８密码子同时出现多态变异，同一地区的６０例正常居民中，无一例检测到该类型多态现象，但２８例高加索居民非癌患者中的６例（２１％）也携带有这种多态等位基因．此外，作者还证实河南食管癌高发区人群中存在第８４位密码子基因多态变异，最近在日本居民中也发现这种变化．这种多态变化导致亮氨酸（ＣＴＴ）变为苯丙氨酸（ＴＴＴ）．８４位密码子的多态变异在中国食管癌患者、中国和高加索非癌患者中的检出率分别为１６％，２０％和３６％，该多态改变与１４３／１７８密码子多态改变同时发生的现象只在１例高加索人ＤＮＡ中被检出．结论ＡＧＴ多态改变可能与食管癌的发生有关，其多态分布可?

AIM To determine missense polymorphism in O 6 alkylguanine alkyltransferase ( AGT ) gene on Chinese subjects in high incidence area for esophageal cancer in Henan, China and on Caucasian subjects. METHODS Polymorphism in O 6 AGT gene was analyzed with PCR SSCP DNA sequencing on Chinese subjects in high incidence area for esophageal cancer in Henan, China and on Caucasian subjects. RESULTS The polymorphic alteration occurred at codon 143 in exon 5, converting isoleucine (ATC) to valine (GTC). The codon 143 polymorphism appeared to be linked to another new polymorphic alteration at codon 178, which converts lysine (AAG) to arginine (AGG). The codon 143/178 polymorphism was found in 2 (2%) of 90 esophageal cancer patients residing in a high incidence area of China, but was not detected in 60 normal subjects residing in the same area. Six of 28 (21%) non cancer Caucasian subjects, however, were found to carry this polymorphic allele. In addition, we confirmed the existence of a codon 84 genetic polymorphism previously identified in a Japanese population, which converts leucine (CTT) to phenylalanine (TTT). The distribution of codon 84 polymorphism was 16%, 20% and 36%, respectively, in the Chinese esophageal cancer patients, and Chinese and Caucasian non cancer subjects. Coexistence of codons 84 and 143/178 polymorphic alterations was found in one Caucasian subject. CONCLUSION Alteration of AGT may play an important role in carcinogenesis, and its distribution may vary with different ethnics.