Allelic deletion at glutathione S-transferase M1 locus and its association with breast cancer susceptibility

Abstract

Glutathione S-transferases (GSTs) are a family of isoenzymes involved in cellular detoxification. Previous studies have correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancer, in heavy smokers. In this study, we determined GSTM1 gene polymorphisms in a French western population of 437 female controls and 361 community breast cancer patients. Three distinct alleles of this gene may be identified: GST M1* A allele, GST M1* B allele, and GST M1* 0 allele (which is deleted). Null patients ( GSTM1 0) are homozygous for the deletion. We determined in our two populations, patients with no, one or two GSTM1 alleles. The comparative analysis of our two populations did not demonstrate any statistically significant difference in GSTM1 allelotype distribution between the two groups ( P=0.43), although the null genotype was the more frequent in patients. The predominance of the null genotype was significant in the oldest group of patients (≥55) ( P=0.006), suggesting that GSTM1 null genotype may play an important role in breast cancer susceptibility in the elderly. This was not observed in the youngest age group, i.e. <40 year old patients ( P=0.25), or in the patients aged from 40 to 55 years old ( P=0.37). Our results also point out a putative protective role of the A allele in the older female control group ( P=0.02), especially in subjects hemizygous for these alleles ( P=0.03). A prospective study will be of interest to investigate the effect of dosage of the gene.