Departments of Medical Statistics, Innsbruck Medical University, Innsbruck, Austria.
Cancer Res. 2010 May 1;70(9):3586-93. doi: 10.1158/0008-5472.CAN-09-3197. Epub 2010 Apr 13.
Epidemiologic studies indicate that elevated levels of gamma-glutamyltransferase (GGT), a key enzyme of glutathione metabolism, might be associated with increased cancer risk. Furthermore, preclinical studies support a role for GGT in tumor invasion and progression. However, the relationship between GGT and risks of cervical intraepithelial neoplasia III (CIN-III) and invasive cervical cancer (ICC) have not been evaluated. We investigated the association of enzymatically determined GGT in blood serum with subsequent incidence of CIN-III and ICC in a prospective population-based cohort of 92,843 women ages 18 to 95, of whom 79% had at least one gynecologic examination including Pap smear testing during follow-up. Cox regression was used to compute adjusted hazard ratios (HR) with 95% confidence intervals for the association of GGT with CIN-III and ICC. During median follow-up of 13.8 years, 702 CIN-III and 117 ICC diagnoses were observed. Compared with normal low GGT (<17.99 units/L), risk of ICC was significantly elevated for all other baseline GGT categories, with adjusted HRs of 2.31 (1.49-3.59) for normal high GGT (18.00-35.99 units/L), 2.76 (1.52-5.02) for elevated GGT (36.00-71.99 units/L), and 3.38 (1.63-7.00) for highly elevated GGT [>72.00 units/L; P trend < 0.0001, HR log unit increase 3.45 (1.92-6.19)]. In contrast, associations between GGT serum levels and CIN-III risk were not statistically significant in the main analysis. Exclusion of the first 2 or 5 years of follow-up did not change the results. Effects did not differ by age, body mass index, or socioeconomic status. Our findings implicate GGT in the progression of premalignant cervical lesions to invasive cancer.
流行病学研究表明，γ-谷氨酰转移酶（GGT）水平升高，这种酶是谷胱甘肽代谢的关键酶，可能与癌症风险增加有关。此外，临床前研究支持 GGT 在肿瘤侵袭和进展中的作用。然而，GGT 与宫颈上皮内瘤变 III 级（CIN-III）和浸润性宫颈癌（ICC）风险之间的关系尚未得到评估。我们研究了在一个前瞻性的、基于人群的 92843 名年龄在 18 至 95 岁的女性队列中，血清中酶法测定的 GGT 与随后发生的 CIN-III 和 ICC 之间的关联，其中 79%的女性在随访期间至少接受了一次妇科检查，包括巴氏涂片检查。使用 Cox 回归计算 GGT 与 CIN-III 和 ICC 之间关联的调整后危险比（HR）和 95%置信区间。在中位随访 13.8 年期间，观察到 702 例 CIN-III 和 117 例 ICC 诊断。与正常低 GGT（<17.99 单位/L）相比，所有其他基线 GGT 类别中 ICC 的风险均显著升高，调整后的 HR 分别为正常高 GGT（18.00-35.99 单位/L）为 2.31（1.49-3.59）、GGT 升高（36.00-71.99 单位/L）为 2.76（1.52-5.02）和高度升高 GGT [>72.00 单位/L]为 3.38（1.63-7.00）；P 趋势<0.0001，HR 对数单位增加 3.45（1.92-6.19）]。相比之下，在主要分析中，GGT 血清水平与 CIN-III 风险之间的关联没有统计学意义。排除随访的前 2 年或前 5 年并没有改变结果。效果不因年龄、体重指数或社会经济地位而不同。我们的研究结果表明，GGT 参与了癌前宫颈病变向浸润性癌症的进展。
