谷胱甘肽S-转移酶基因座GSTM3的多态性：与细胞色素P450和谷胱甘肽S-转移酶基因型的相互作用作为多发性皮肤基底细胞癌的危险因素。

Polymorphism at the glutathione S-transferase locus GSTM3: interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma.

作者信息

Yengi L, Inskip A, Gilford J, Alldersea J, Bailey L, Smith A, Lear J T, Heagerty A H, Bowers B, Hand P, Hayes J D, Jones P W, Strange R C, Fryer A A

机构信息

Clinical Biochemistry Research Group, School of Postgraduate Medicine, Keele University, Stoke-on-Trent, Staffordshire, England.

出版信息

Cancer Res. 1996 May 1;56(9):1974-7.

PMID:8616834

Abstract

The influence of polymorphism in the glutathione S-transferase, GSTM3 gene on susceptibility to cutaneous basal cell carcinoma (BCC) has been investigated. We have reported previously two GSTM3 alleles, GSTM3A and GSTM3B, distinguished by a recognition motif for the YY1 transcription factor in GSTM3B. In this study, immunohistochemistry was used to identify GSTM3 expression in the epidermis of skin samples from 11 controls and 9 patients with BCC. A PCR method was used to identify GSTM3A and GSTM3B and thereby the GSTM3 AA, GSTM3 AB, and GSTM3 BB genotypes in 300 controls and 286 Caucasians with 1-35 primary BCCs. Genotypes at GSTM1, GSTT1, and the cytochrome P450 CYP1A1 and CYP2D6 loci were also determined. Frequencies of GSTM3, GSTM1, GSTT1, CYP2D6, and CYP1A1 genotypes in the cases and controls were not different. Dividing the BCC cases into groups of 92 patients with 1 lesion and 194 patients with 2-35 lesions showed that the frequencies of GSTM3 BB (2.6%) and GSTM1 A/B (1.3%) in the group with 2-35 tumors were almost significantly lower than in the group with 1 lesion (7.6%, exact P = 0.0601, chi 2(1) = 3.390; 6.5%, exact P = 0.055, chi 2(1) = 4.946, respectively). Within the cases with 2-35 tumors, a Poisson regression model was used to identify genotypes, characteristics such as skin type, and interactions between genotypes and characteristics associated with increasing numbers of tumors. This showed, after correction for male gender and age, that GSTM3 AA was not associated with risk of increased numbers of tumors, although in combination with skin type 1, GSTM1 null, and CYP1A1 m1m1, the genotype did confer increased risk (P < 0.001, rate ratio, 2.058; P < 0.001, rate ratio, 1.606; P < 0.001, rate ratio, 1.470 respectively). The data suggest that, like other allelic GST, GSTM3 influences cancer risk. As GSTM3 AA was associated with increased tumor numbers, it appears that YY1 acts as an activator of the recognition motif in GSTM3B.

摘要

谷胱甘肽S-转移酶GSTM3基因多态性对皮肤基底细胞癌（BCC）易感性的影响已得到研究。我们之前报道过两个GSTM3等位基因，GSTM3A和GSTM3B，它们的区别在于GSTM3B中YY1转录因子的识别基序。在本研究中，采用免疫组织化学法鉴定了11名对照者和9名BCC患者皮肤样本表皮中的GSTM3表达。采用聚合酶链反应（PCR）方法鉴定GSTM3A和GSTM3B，从而确定300名对照者和286名患有1 - 35个原发性BCC的白种人的GSTM3 AA、GSTM3 AB和GSTM3 BB基因型。还测定了GSTM1、GSTT1以及细胞色素P450 CYP1A1和CYP2D6基因座的基因型。病例组和对照组中GSTM3、GSTM1、GSTT1、CYP2D6和CYP1A1基因型的频率没有差异。将BCC病例分为92名有1个病灶的患者组和194名有2 - 35个病灶的患者组，结果显示，在有2 - 35个肿瘤的组中，GSTM3 BB（2.6%）和GSTM1 A/B（1.3%）的频率几乎显著低于有1个病灶的组（分别为7.6%，确切P = 0.0601，卡方(1)=3.390；6.5%，确切P = 0.055，卡方(1)=4.946）。在有2 - 35个肿瘤的病例中，采用泊松回归模型来确定基因型、皮肤类型等特征以及基因型与特征之间与肿瘤数量增加相关的相互作用。这表明，在校正男性性别和年龄后，GSTM3 AA与肿瘤数量增加的风险无关，尽管与1型皮肤、GSTM1缺失和CYP1A1 m1m1组合时，该基因型确实会增加风险（P < 0.001，率比为2.058；P < 0.001，率比为1.606；P < 0.001，率比为1.470）。数据表明，与其他等位基因GST一样，GSTM3影响癌症风险。由于GSTM3 AA与肿瘤数量增加相关，似乎YY1作为GSTM3B中识别基序的激活剂发挥作用。