Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women

Abstract

Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n=615) or fibrocystic breast conditions (n=467) were compared to women without clinical breast disease (n=878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105-Val allele (OR=1.33, 95% CI, 0.99-1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who have breast cancer with extra-tumoral tissue proliferation (OR=1.77, 95% CI, 1.03-3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105-Val allele needs confirmation in other studies.

Detection and relevance of germline genetic polymorphisms in glutathione S-transferases (GSTs) in breast cancer patients from northern Indian population

“…Another recent Chinese study found no association of either GSTM1 null genotype or GSTP1 Ile105Val polymorphism with the risk of breast cancer. However, when the GSTM1 and GSTP1 genotypes were examined in combination, there was some suggestion of a slight increase in breast cancer risk for women carrying the GSTM1 null genotype and at least one GSTP1 Val allele [38]. These results are consistent with our findings when these two genotypes were examined in combination (data not shown).…”

Genetic polymorphisms and haplotype of hormone-related genes are associated with the risk of breast cancer in Chinese women

“…Reding et al (2009) showed that the GSTP1 rs1695 A allele was a protective factor for BC compared with the G allele, but several other studies found no association between rs1695 and BC risk (Ramalhinho et al, 2011;Liu et al, 2013). Zhang et al (2011) reported that the minor allele homozygotes of rs1695 (GG) were associated with an increased risk of developing BC, which is consistent with three other studies in Chinese women (Chang et al, 2006;Lee et al, 2008;Sakoda et al, 2008). Liu et al (2013) found that GSTP1 rs1695 was associated with BC risk in an Asian population, but not in Caucasians or Africans.…”

Genetic variants in GSTM3 gene within GSTM4-GSTM2-GSTM1-GSTM5-GSTM3 cluster influence breast cancer susceptibility depending on GSTM1

“…Enzymes involved in the metabolism of steroid hormones and their metabolites, such as glutathione-S-transferases (GSTs), are of particular interest in the study of breast cancer susceptibility [5,6]. The GST superfamily belongs to the group of phase II enzymes, acting in coordination with phase I enzymes in carcinogen metabolism [5].…”