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Association of Homozygous Wild-Type Glutathione S-Transferase M1 Genotype with Increased Breast Cancer Risk

Departments of¹ Pathology, ² Preventive Medicine and Biostatistics, and ³ Molecular Physiology and Biophysics, Program in Human Genetics and Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee

More than 500 studies have examined the association of the glutathione S-transferase M1 (GSTM1) genotype with various malignancies yielding inconsistent results. The genotyping was based on a PCR assay that identified the GSTM1 null (-/-) genotype but did not distinguish homozygous wild-type (+/+) and heterozygous (+/-) individuals. We developed an assay that allowed the definition of +/+, +/-, and -/- genotypes by separate identification of wild-type and null alleles, which were found with frequencies of 0.225 and 0.775, respectively, in Caucasian women. We applied the new assay to a breast cancer case-control study and identified the +/+ genotype in 14 (6.9%) of 202 control subjects compared with 37 (18.2%) of 203 patients. Compared with women with the -/- genotype, the relative risk of breast cancer for the +/+ genotype was 2.83 (95% confidence interval, 1.45–5.59; P = 0.002), suggesting a protective effect of the GSTM1 deletion.

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