De Roos Anneclaire J, Rothman Nathaniel, Brown Merideth, Bell Douglas A, Pittman Gary S, Shapiro William R, Selker Robert G, Fine Howard A, Black Peter M, Inskip Peter D
Fred Hutchinson Cancer Research Center and University of Washington Department of Epidemiology, Seattle, WA 98109, USA.
Neuro Oncol. 2006 Apr;8(2):145-55. doi: 10.1215/15228517-2005-003. Epub 2006 Jan 27.
Genes involved in phase I and phase II regulation of aromatic hydrocarbon-induced effects exhibit sequence variability that may mediate the risk of adult brain tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3, EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994 to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples collected from 1277 subjects, and genotyping was conducted for CYP1A1 I462V, CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/*B (intron 6 deletion), and NQO1 P187S. The CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3 *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI, 1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated with GSTM3 *B/*B were observed in younger subjects (age < 50) and older subjects (age > or = 50), in men and women, and within each study site. The magnitude of association for GSTM3 with glioma and meningioma was greater among ever-smokers than among those who had never smoked. None of the other genotypes showed consistent associations with any tumor type. The association with the GSTM3 *B allele, while intriguing, requires replication, and additional research is needed to clarify the function of the GSTM3 alleles studied here.
参与芳烃诱导效应的I期和II期调控的基因表现出序列变异性，这可能介导成人大脑肿瘤的风险。我们评估了CYP1A1、CYP1B1、GSTM3、EPHX1和NQO1基因变异与成人大脑肿瘤发病率之间的关联。病例为1994年至1998年在美国三家医院诊断的胶质瘤患者（n = 489）、脑膜瘤患者（n = 197）或听神经瘤患者（n = 96）。对照为因非恶性疾病入住同一家医院的799名患者。从1277名受试者采集的血液样本中提取DNA，并对CYP1A1 I462V、CYP1B1 V432L、EPHX1 Y113H、GSTM3 *A/*B（内含子6缺失）和NQO1 P187S进行基因分型。CYP1B1 V432L纯合变异与脑膜瘤风险降低相关（优势比[OR]=0.6；95%可信区间，0.3 - 1.0），但与其他肿瘤类型无关。GSTM3 *B/*B基因型与胶质瘤风险增加相关（OR = 2.3；95%可信区间，1.0 - 5.2）和脑膜瘤风险增加相关（OR = 3.6；95%可信区间，1.3 - 9.8）。在较年轻受试者（年龄<50岁）和较年长受试者（年龄≥50岁）、男性和女性以及每个研究地点中均观察到与GSTM3 *B/*B相关的风险增加。与从未吸烟者相比，曾经吸烟者中GSTM3与胶质瘤和脑膜瘤的关联程度更大。其他基因型均未显示与任何肿瘤类型有一致的关联。与GSTM3 *B等位基因的关联虽然有趣，但需要重复验证，并且需要进一步研究以阐明此处研究的GSTM3等位基因的功能。
