Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset.
The M1 member of the Mu subclass of glutathione S-transferase (GSTM1) is only expressed in about 50% of individuals. In contrast, GSTT1, a member of the theta class which has been recently shown to be polymorphic, is expressed in 85% of Australian individuals. Previous studies have shown a significant excess of homozygous null GSTM1 genotypes among individuals with colorectal cancer, particularly those with proximal tumours. This suggests that GSTM1 plays a role in susceptibility to this neoplasm. In this study of 132 individuals with colorectal cancer and 200 controls, no significant excess of GSTM1 homozygous null genotypes was found among colorectal cancer patients with either a proximal or distal tumour. This suggests that the association between GSTM1 homozygous null genotypes and colorectal cancer is of smaller effect than has been reported previously using larger sample sizes. We have also examined the frequency of homozygous null GSTT1 genotypes in patients with colorectal cancer. Although the frequency was not significantly different in cases compared to control individuals, GSTT1 null homozygotes were significantly more common in patients who were diagnosed before the age of 70 years than in those who were diagnosed at an older age. This suggests that the GSTT1 genotype, and perhaps also the GSTM1 genotype for which a similar, but non-significant effect was seen, might influence the age of onset of colorectal cancer.
Chenevix-Trench
G
G
Queensland Institute of Medical Research, Brisbane, Australia.
Young
J
J
Coggan
M
M
Board
P
P
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics*; D000368:Aged; D000375:Aging / Q000502:physiology*; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D017353:Gene Deletion; D016259:Genes, myc; D011905:Genes, ras; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D007527:Isoenzymes; D005982:Glutathione Transferase