Polymorphisms of glutathione S-transferase M1, T1 and P1 in patients with reflux esophagitis and Barrett’s esophagus

Abstract

Reflux esophagitis (RE) and Barrett's esophagus (BE) belong to the most common esophageal complications of gastroesophageal reflux disease. Glutathione S-transferase (GST) enzymes play an important role in cellular protection against oxidative stress and toxic foreign chemicals. Therefore, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes could influence susceptibility to RE and BE. GSTM1, GSTT1 and GSTP1 loci were analyzed by PCR-based methods in 64 patients with RE (and an additional group of 22 subjects with BE as the fourth grade of esophagitis) and 173 unrelated controls. There were no significant differences in the distributions of GSTM1 and GSTT1 genotypes between the controls and patients with RE or BE. Similarly, frequencies of GSTP1 alleles were non-significantly different between the control and RE groups. However, GSTP1 B allele carriers were more frequent among the patients with BE compared to those in the reflux esophagitis group (P = 0.04, OR = 2.10, 95% CI 0.99-4.44) and most significantly when compared to the controls (P = 0.0067, P corr < 0.05, OR = 2.56, 95%CI 1.30-5.05). Although the GSTM1 and GSTT1 genes did not show any relationship with reflux disease, the GSTP1 gene might be one of the risk factors associated with susceptibility to RE, especially to BE.

Genetic factors in the pathogenesis of gastroesophageal reflux disease

“…Individuals homozygous for the null allele lack GST enzyme activity and hence may not be able to detoxify the chemicals [29,30]. However, GSTT1 and GSTM1 polymorphisms may not be associated with risk of GERD, though GSTP1 b allele was associated with susceptibility to GERD [31], especially to BE [32].…”

Genetic predisposition to gastro-oesophageal cancer

“…Similarly to SCC, it has been postulated that polymorphisms in enzymes involved in the detoxification of xenobiotics and luminal toxic agent might be associated with an increased risk. Four out of five studies reported an increased risk associated with the presence of allelic variant of glutathione-S transferase GSTP1, GSTM1 and GSTT1; the data are however inconclusive [44][45][46][47]; especially since allelic variants from these enzymes were also demonstrated not to have any statistical association with risk [44][45][46][47][48]. As a key regulator of cell cycle progression, cyclin D1 polymorphisms have been investigated in the context of Barrett's carcinogenesis.…”

Polymorphisms in genes of the steroid hormone biosynthesis and metabolism pathways and endometrial cancer risk

“…Therefore, COMT is a key enzyme for preventing quinone and semiquinone formation via the methylation of hydroxyestrogens [13]. GSTs, SULTs and UGTs inactivate any quinones or semiquinones formed, ultimately lending to their elimination [14][15][16][17][18].…”