Association Of GSTM1, GSTT1 And GSTP1 Polymorphisms With Breast Cancer Among Jordanian Women

Abstract

Purpose: Genetic predisposition to disease has become one of the most investigated risk factors in recent years, and breast cancer (BC) is no exception. In this study, we investigated specific genetic variants of three candidate genes belonging to the glutathione-S-transferase superfamily that have been implicated in increased risk of cancers.

Materials and methods: This case-control study comprised 241 Jordanian women who were diagnosed with BC in addition to 219 matched controls. Gel electrophoresis of PCR products was used to visualize and genotype both the GSTM1 and GSTT1 genes, while PCR-RFLP was employed to genotype the rs1695 of the GSTP1 gene.

Results: Our findings did not reveal any correlation between the investigated polymorphisms of GST genes and BC risk among Jordanian women. Otherwise, the combination of GSTM1 entire gene deletion and (GG) genotype of GSTP1 polymorphism (rs1695) was significantly associated with BC with p-value <0.05 (i.e. p-value was not significant after correcting for multiple comparison).

Conclusion: We suggest that the interaction between GSTM1 polymorphism and rs1695 of GSTP1 may influence BC development and progression among Jordanian women. More epidemiological studies are needed to provide a baseline for the underlying role of GSTs polymorphisms in tumorigenesis.

Keywords: GST genes; breast; cancer; genetic variation; polymorphisms.

Figure 1

GSTM1 genotypes detected by agarose gel electrophoresis. Case one represents a homozygous presence indicated by a 625 bp band in the GSTM1 lane but no band in the GSTM1 deletion lane. The double deletion is represented by one band (4.748 kpb size) in theGSTM1 deletion lane (case 3). Case two shows the heterozygous genotype (presence/deletion).

Figure 2

GSTT1 genotypes detected by agarose gel electrophoresis. Case one represents the homozygous presence indicated by a 969 bp band in the GSTM1 presence lane but no band in theGSTT1 deletion lane. The double deletion is represented by one band (3.106 kbp size) in the GSTM1 deletion lane (case 3). Case two shows the heterozygous genotype (presence/deletion).

Figure 3

GSTP1 genotypes detected by agarose gel electrophoresis. Lane 1 represents the wild-type genotype (A/A) with two bands at 329 and 107 bp. Lane 2 illustrates 3 bands at 329, 222, and 107 bp and represents the heterozygous genotype (A/G). Lane 3 depicts the homozygous mutant genotype (G/G) with two bands at 222 and 107 bp.