Park L Y, Muscat J E, Kaur T, Schantz S P, Stern J C, Richie J P, Lazarus P
Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Pharmacogenetics. 2000 Mar;10(2):123-31. doi: 10.1097/00008571-200003000-00004.
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 mu 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.
谷胱甘肽S-转移酶（GST）μ类基因中的两个成员，即GSTM1和GSTM3，具有多态性等位基因，这些等位基因与GSTμ蛋白表达水平的改变有关，并且可能与几种烟草相关癌症的风险增加有关。口腔癌是一种与烟草相关的疾病，非洲裔美国男性的发病率明显高于白种人男性。为了研究GSTM多态性在非洲裔美国人和白种人患口腔癌风险中的潜在作用，我们检测了63名经组织学确诊为原发性口腔癌的非洲裔美国患者和101名白种人患者，以及133名非洲裔美国人和213名白种人匹配对照者中GSTM1缺失和GSTM3内含子6多态性的发生率。在非洲裔美国人中，与GSTM1（0/0）基因型相关的口腔癌优势比为3.1[95%置信区间（CI）=1.1-8.5]，GSTM1（0/0）基因型与口腔癌风险之间的关联在重度吸烟者中最强[即>24包年；优势比（OR）=5.4，95%CI=1.2-24]。以潜在的最具保护作用的GSTM1[+]/GSTM3（B/B）基因型作为参照组，在具有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）和GSTM1（0/0）/GSTM3[（A/A）+（A/B）]（OR=6.6，95%CI=1.2-38）基因型的非洲裔美国人中观察到口腔癌风险增加（P<0.01，趋势检验）。在白种人中未观察到GSTM基因型与口腔癌风险之间的显著关联。这些结果表明，GSTM1缺失和GSTM3内含子6多态性在非洲裔美国人患口腔癌的风险中起重要作用，并表明GSTμ类是该人群中重要的烟草致癌物解毒酶。
