Polymorphic expression of the glutathione S-transferase P1 gene and susceptibility to Barrett's esophagus and esophageal carcinoma

Esther M.M. Van Lieshout, Hennie M. J. Roelofs, Simone Dekker, Chris J. J. Mulder, Theo Wobbes, Jan B.M.J. Jansen, Wilbert H.M. Peters

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Factors determining individual susceptibility to esophageal cancer or premalignant Barrett’s epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYPIA1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYPIA1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett’s epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Ψ2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYPIA1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett’s epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett’s epithelium and adenocarcinoma.
Original languageEnglish
Article number3
Pages (from-to)586–589
Number of pages59
JournalCancer Research
Volume59
Issue number3
Publication statusPublished - 1 Feb 1999
Externally publishedYes

Bibliographical note

©1999 American Association for Cancer Research.

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