Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15232, USA.
Cancer Epidemiol. 2013 Aug;37(4):505-11. doi: 10.1016/j.canep.2013.02.009. Epub 2013 Mar 21.
Functional polymorphisms in drug metabolizing enzymes (DMEs) may be determinants of survival in oral and oropharyngeal squamous cell carcinoma (OOSCC).
OOSCC cases (N=159) with a history of either tobacco or alcohol use were genotyped for polymorphisms in eight DMEs. Overall and disease-specific survival were analyzed using Kaplan-Meier plots and the log-rank test. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) in exploratory analyses of patient subgroups.
Kaplan-Meier analyses showed N-acteyltransferase-2 (NAT2) fast acetylators experienced a 19.7% higher 5-year survival rate than slow acetylators (P=0.03) and this association was similar in oropharyngeal and oral cancer. After multiple adjustment, including tumor site and stage, the NAT2 fast acetylator phenotype was associated with improved overall survival (vs. slow acetylators) provided chemotherapy or radiation were not used (HR, 0.26; 95% CI, 0.10-0.66). However, NAT2 phenotype was unrelated to survival in patients treated with chemoradiotherapy (HR, 1.21; 95% CI, 0.54-2.73) or radiotherapy (HR, 0.67; 95% CI, 0.31-1.59) (P-for-NAT2/treatment-interaction=0.04). Normal activity GSTP1 was associated with a 19.2% reduction in 5-year disease-specific survival relative to reduced activity GSTP1 (P=0.04) but this association was not modified by treatment.
Our results suggest that functional polymorphisms in NAT2 and GSTP1 are associated with OOSCC survival. Confirmation of these results in larger studies is required.
药物代谢酶（DME）的功能多态性可能是口腔和口咽鳞状细胞癌（OOSCC）患者生存的决定因素。
对有吸烟或饮酒史的 159 例 OOSCC 病例进行了 8 种 DME 多态性的基因分型。使用 Kaplan-Meier 图和对数秩检验分析总生存和疾病特异性生存。在探索性患者亚组分析中，使用 Cox 比例风险回归计算危险比（HR）和 95%置信区间（CI）。
Kaplan-Meier 分析显示，N-乙酰基转移酶-2（NAT2）快乙酰化剂的 5 年生存率比慢乙酰化剂高 19.7%（P=0.03），这种关联在口咽癌和口腔癌中相似。经过多变量调整，包括肿瘤部位和分期，NAT2 快乙酰化表型与未接受化疗或放疗的患者的总生存改善相关（与慢乙酰化剂相比）（HR，0.26；95%CI，0.10-0.66）。然而，NAT2 表型与接受放化疗（HR，1.21；95%CI，0.54-2.73）或放疗（HR，0.67；95%CI，0.31-1.59）的患者的生存无关（NAT2/治疗相互作用的 P 值=0.04）。正常活性 GSTP1 与 5 年疾病特异性生存率降低 19.2%相关，而 GSTP1 活性降低（P=0.04），但这种关联不受治疗的影响。
我们的研究结果表明，NAT2 和 GSTP1 的功能多态性与 OOSCC 患者的生存有关。需要在更大的研究中对这些结果进行验证。
