Two members of the mu class of glutathione S-transferase (GST) genes, GSTM1 and GSTM3, have polymorphic alleles which have been associated with altered levels of GST μ protein expression and may be linked to increased risk for several tobacco-related cancers. Oral cancer is a tobacco-related disease that affects African-American men at a significantly higher incidence than Caucasian men. To examine the potential role of GSTM polymorphisms in risk for oral cancer in African-Americans and Caucasians, the prevalences of the GSTM1 null and GSTM3 intron 6 polymorphisms were examined in 63 African-American and 101 Caucasian patients with histologically confirmed primary oral cancer, as well as in 133 African-American and 213 Caucasian matched control subjects. In African-Americans, the odds ratio for oral cancer associated with the GSTM1 (0/0) genotype was 3.1 [95% confidence interval (CI) = 1.1–8.5], with the association between the GSTM1 (0/0) genotype and oral cancer risk strongest in heavy smokers [i.e. > 24 pack-years; odds ratio (OR) = 5.4, 95% CI = 1.2–24]. Using the potentially most protective GSTM1 [+]/ GSTM3 (B/B) genotype as the reference group, increased risk for oral cancer was observed in African-Americans with the GSTM1 [+]/ GSTM3 [(A/A) + (A/B)] (OR = 2.2, 95% CI = 0.82–6.0), GSTM1 (0/0)/ GSTM3 (B/B) (OR = 4.3, 95% CI = 1.1–16), and GSTM1 (0/0)/ GSTM3 [(A/A) + (A/B)] (OR = 6.6, 95% CI = 1.2–38) genotypes (P < 0.01, trend test). No significant associations were observed between GSTM genotype and oral cancer risk in Caucasians. These results suggest that the GSTM1 null and GSTM3 intron 6 polymorphisms play an important role in risk for oral cancer among African-Americans and implicates the mu class of GSTs as important tobacco carcinogen detoxifying enzymes in this population.
aDepartment of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, Divisions of bEpidemiology and cNutritional Carcinogenesis, American Health Foundation, New York, dHead and Neck Service, Memorial Sloan-Kettering Cancer Center, New York and eDepartment of Otolaryngology, The New York Eye and Ear Infirmary, New York, USA
Received 28 May 1999 accepted 14 July 1999
Correspondence to Philip Lazarus, H. Lee Moffitt Cancer Center and Research Institute, MRC-3E, 12902 Magnolia Drive, Tampa, FL 33612, USA Fax: +1 813 903 6817; e-mail: firstname.lastname@example.org