Polymorphism of the Pi class glutathione S-transferase in normal populations and cancer patients

被引:164
|
作者
Harris, MJ
Coggan, M
Langton, L
Wilson, SR
Board, PG
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, Mol Genet Grp, Canberra, ACT 2601, Australia
[2] Australian Natl Univ, Ctr Math & Its Applicat, Canberra, ACT 2601, Australia
来源
PHARMACOGENETICS | 1998年 / 8卷 / 01期
关键词
cancer susceptibility; glutathione S-transferase P1-1; M1-1; polymorphism;
D O I
10.1097/00008571-199802000-00004
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Deficiencies of the glutathione transferase isoenzymes GSTM1-1 and GSTT1-1 have been shown to be risk modifiers in a number of different cancers but there have been no similar studies with GSTP1-1, the only member of the Pi class of glutathione S-transferases expressed in humans. Over-expression of GSTP1-1 in tumours suggests that it may be a significant factor in acquired resistance to certain anticancer drugs. We previously identified a cDNA clone with two amino acid substitutions (I-105 V, A(114)V). This clone suggests that the GSTP1 gene is polymorphic and it is possible that the different genotypes may be associated with altered cancer risk or drug resistance. In the present study, we report methods for genotyping individuals at codons 105 and 114 of GSTP1 and demonstrate that these two loci are polymorphic in several different racial groups. We also detected significant linkage disequilibrium between these two loci. To determine if either of the alleles at these two loci were associated with altered cancer susceptibility, we genotyped individuals with colorectal cancer or lung cancer. A total of 131 colorectal and 184 lung cancer patients were compared with 199 control individuals. Overall, there were no significant associations between the GSTP1 polymorphisms and either form of cancer. (C) 1998 Chapman & Hall Ltd.
引用
收藏
页码:27 / 31
页数:5
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