The impact of GSTM1/GSTT1 polymorphism for the risk of oral cancer.

Abstract

Since development of oral squamous cell cancer (OSCC) is triggered by various noxa, different variants of the antioxidant glutathione S-transferases (GSTs) can counteract toxic compounds (e.g., tobacco smoke). Because different polymorphisms of GST are known to have an increased sensitivity to carcinogenic agents, the aim of this study was to analyze whether GSTM1 or GSTT1 polymorphisms increase the risk for the development of OSCC. GSTM1 and GSTT1 polymorphism was examined in healthy volunteers (n = 93) and in patients with OSCC (n = 100) by PCR after brush biopsy of oral mucosa. Odds ratio (OR) was calculated to evaluate the risk of oral cancer development. GSTM1 and GSTT1 deletion was found in 57% (53/93) and 18% (17/93), respectively, in healthy patients, while the OSCC group showed 57% (57/100) for GSTM1 deletion and 22% (22/100) with a deletion of GSTT1. Odds ratio for GSTM1 polymorphism was 1.00 and for GSTT1 1.26. Comparing smokers and nonsmokers with GSTM1 deletion polymorphism, OR was 4.35, while smokers without GSTM1 deletion showed an OR of 1.45. Adapting these data to the smoking habits of the general population in Germany, the OR was 9.25 for smokers with a GSTM1 deletion and OR 6.68 for smokers without a GSTM1 deletion. In smokers with GSTT1 deletion polymorphism, OR was 1.6 (adapted to the smoking habits of the general population: OR 6.16) and 3.16 (OR 8.56) in smokers without deletion in GSTT1 gene. Analysis of GST-M1 polymorphism in smokers could help to identify patients with a higher risk for the development of oral cancer. Early detection of OSCC due to a close meshed monitoring program for patients with GST-M1 polymorphism could help to improve the patient outcome. For polymorphism investigations, the oral brush biopsy is a sufficient method to gain DNA material.