Yale University School of Public Health, 60 College Street, New Haven, CT 06520-8034, USA.
Am J Hematol. 2010 Jan;85(1):51-6. doi: 10.1002/ajh.21580.
Metabolic pathway enzymes, such as Cytochrome P450 (CYP), glutathione S-transferase (GST), and N-acetyltransferases (NAT) are involved in activation and detoxification of environmental carcinogens as well as drug metabolism. We hypothesized that the genetic variations in such metabolic pathways may affect NHL prognosis and survival. Follow-up information of 496 female NHL incident cases diagnosed during 1996-2000 in Connecticut were abstracted from the Connecticut Tumor Registry in 2008; survival analyses were conducted by comparing the Kaplan-Meier curves, and hazard ratios (HR) were computed from the Cox Proportional Hazard models adjusting for demographic and tumor characteristics which were suggested by previous studies to be determinants of NHL survival. We identified six SNPs from four metabolism genes (CYP2E1, GSTP1, GSTT1, and NAT1) that were associated with NHL survival. Specifically, polymorphisms in GSTT1 were associated with follicular lymphoma survival; and polymorphisms in CYP2E1, GSTP1, and NAT1 were associated with survival of chronic lymphocytic leukemia/small lymphocytic lymphoma. Our study suggests that genetic polymorphisms in metabolic pathways may help improve the prediction of NHL survival and prognosis.
代谢途径酶，如细胞色素 P450（CYP）、谷胱甘肽 S-转移酶（GST）和 N-乙酰基转移酶（NAT），参与环境致癌物的激活和解毒以及药物代谢。我们假设这些代谢途径中的遗传变异可能会影响 NHL 的预后和生存。2008 年，我们从康涅狄格州肿瘤登记处提取了 1996-2000 年期间在康涅狄格州诊断出的 496 名女性 NHL 发病病例的随访信息；通过比较 Kaplan-Meier 曲线进行生存分析，并根据先前研究建议的人口统计学和肿瘤特征对 Cox 比例风险模型进行调整，计算危险比（HR），这些特征被认为是 NHL 生存的决定因素。我们从四个代谢基因（CYP2E1、GSTP1、GSTT1 和 NAT1）中确定了六个与 NHL 生存相关的 SNP。具体来说，GSTT1 中的多态性与滤泡性淋巴瘤的生存有关；而 CYP2E1、GSTP1 和 NAT1 中的多态性与慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的生存有关。我们的研究表明，代谢途径中的遗传多态性可能有助于改善 NHL 生存和预后的预测。
