Glutathione S-transferase genotypes and cancer risk.

Over 500 studies have examined the association of genetic variants of glutathione S-transferases with various malignancies yielding inconsistent results. The genotyping was based on PCR assays that identified the GSTM1 and GSTT1 null (-/-) genotypes but did not distinguish homozygous wild-type +/+ and heterozygous +/- individuals. Complete GSTM1 and GSTT1 genotyping can be accomplished by recently developed assays [Cancer Res. 64 (2004) 1233-1236; Pharmacogenetics 10 (2000) 557-565] that allow the definition of +/+, +/-, and -/- genotypes by separate identification of the respective GSTM1 and GSTT1 wild-type and null alleles. Application of the new GSTM1 assay to a breast cancer case-control study revealed that the relative risk of breast cancer for the +/+ genotype compared to the -/- genotype was 2.83 (95% confidence interval 1.45-5.59; P=0.002), suggesting a protective effect of the GSTM1 deletion [Cancer Res. 64 (2004) 1233-1236]. Regardless of the explanation for the association between the +/+ genotype and increased breast cancer risk, these results warrant application of true GSTM1 and GSTT1 genotyping to additional or previously analyzed groups with breast cancer or other malignancies.