Chan Queeny K Y, Khoo Ui-Soon, Ngan Hextan Y S, Yang Chong-Qing, Xue Wei-Cheng, Chan Kelvin Y K, Chiu Pui-Man, Ip Philip P C, Cheung Annie N Y
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Clin Cancer Res. 2005 Apr 15;11(8):2981-5. doi: 10.1158/1078-0432.CCR-04-2038.
Endometrial carcinoma is the most common gynecologic cancer in developed countries. Prolonged unopposed estrogen exposure has been identified as the major risk factor. The pi-class glutathione S-transferase (GSTP1) is a phase II metabolic enzyme that is important in the detoxification of a wide range of electrophiles including carcinogenic steroid-hormone intermediates generated through oxidative metabolism. In this study, we aimed at determining the association between the GSTP1 polymorphism and the risk of endometrial carcinoma in a Chinese population.
Genotyping of 180 cases and 200 age-matched controls were assessed by PCR-RFLP approach and confirmed by direct sequencing.
Statistical analysis showed that patients of valine allele carriers had 2.03-fold of increased risk of developing endometrial carcinoma (P < 0.01). The allele frequencies for the Ile and Val variants between the cancer cases and controls were also significantly different (P < 0.01; odds ratio, 1.59; 95% confidence interval, 1.13-2.23). Such association was shown in endometrial cancers as a group and in type I endometrioid adenocarcinoma but not the type II nonendometrioid adenocarcinoma. In addition, the Val allele was found significantly associated with high-grade endometrial cancer and/or endometrial cancer of deep myometrial invasion (P < 0.01). Interestingly, the relatively low frequency of Val/Val genotype in both the cancer cases and controls, in parallel with the lower incidence of endometrial cancer in Chinese, was observed when compared with those in Caucasians.
Our findings suggested that the GSTP1 Ile(105)Val polymorphism was associated with an increased risk of endometrial cancer. Further studies may be required to explore the possible significance of these polymorphisms on GSTP1-related metabolism that may affect the susceptibility of Asians to endometrial carcinoma.
子宫内膜癌是发达国家最常见的妇科癌症。长期无对抗的雌激素暴露已被确定为主要危险因素。π类谷胱甘肽S-转移酶（GSTP1）是一种II期代谢酶，在多种亲电试剂的解毒过程中起重要作用，这些亲电试剂包括通过氧化代谢产生的致癌甾体激素中间体。在本研究中，我们旨在确定中国人群中GSTP1基因多态性与子宫内膜癌风险之间的关联。
采用PCR-RFLP方法对180例病例和200例年龄匹配的对照进行基因分型，并通过直接测序进行确认。
统计分析表明，缬氨酸等位基因携带者患子宫内膜癌的风险增加2.03倍（P<0.01）。癌症病例组与对照组之间异亮氨酸和缬氨酸变体的等位基因频率也有显著差异（P<0.01；优势比，1.59；95%置信区间，1.13-2.23）。这种关联在子宫内膜癌总体以及I型子宫内膜样腺癌中存在，但在II型非子宫内膜样腺癌中不存在。此外，发现缬氨酸等位基因与高级别子宫内膜癌和/或肌层深部浸润性子宫内膜癌显著相关（P<0.01）。有趣的是，与白种人相比，癌症病例组和对照组中Val/Val基因型的频率相对较低，这与中国子宫内膜癌发病率较低情况相符。
我们的研究结果表明，GSTP1 Ile(105)Val基因多态性与子宫内膜癌风险增加有关。可能需要进一步研究来探索这些多态性对GSTP相关代谢的潜在意义，这可能影响亚洲人对子宫内膜癌的易感性。
