Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Pharmacogenomics J. 2011 Aug;11(4):292-9. doi: 10.1038/tpj.2010.38. Epub 2010 Jun 1.
Glutathione-S-transferase T1 (GSTT1) and GSTM1 detoxify carcinogens and thus potentially contribute to inter-individual susceptibility to cancer. We determined the ability of GST copy number variation (CNV) to predict the risk of cancer in the general population. Exact copy numbers of GSTT1 and GSTM1 were measured by real-time PCR in 10 247 individuals, of whom 2090 had cancer. In men, the cumulative incidence of prostate cancer increased and the cumulative 5-year survival decreased with decreasing GSTT1 copy numbers (trends=0.02). The hazard ratios (HRs) (95% CIs) for prostate cancer and for death after prostate cancer diagnosis were, respectively, 1.2 (0.8-1.8) and 1.2 (0.6-2.1) for GSTT11/0, and 1.8 (1.1-3.0) and 2.2 (1.1-4.4) for GSTT10/0 versus GSTT11/1. In women, the cumulative incidence of corpus uteri cancer increased with decreasing GSTT1 copy numbers (trend=0.04). The HRs for corpus uteri cancer were, respectively, 1.8 (1.0-3.2) and 2.2 (1.0-4.6) for GSTT11/0 and GSTT10/0 versus GSTT11/1. Finally, the cumulative incidence of bladder cancer increased, and the cumulative 5-year survival decreased, with decreasing GSTM1 copy numbers (P=0.03-0.05). The HRs for bladder cancer were, respectively, 1.5 (0.7-3.2) and 2.0 (0.9-4.3) for GSTM11/0 and GSTM10/0 versus GSTM11/1. The HR for death after bladder cancer diagnosis was 1.9 (1.0-3.7) for GSTM10/0 versus GSTM1*1/0. In conclusion, exact CNV in GSTT1 and GSTM1 predict incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer.
谷胱甘肽 S-转移酶 T1（GSTT1）和 GSTM1 可以解毒致癌物质，因此可能会影响个体对癌症的易感性。我们确定 GST 拷贝数变异（CNV）是否能够预测普通人群患癌症的风险。通过实时 PCR 测量了 10247 个人的 GSTT1 和 GSTM1 的精确拷贝数，其中 2090 人患有癌症。在男性中，随着 GSTT1 拷贝数的减少，前列腺癌的累积发病率增加，5 年生存率降低（趋势=0.02）。前列腺癌的风险比（HRs）（95%CI）分别为 GSTT11/0 为 1.2（0.8-1.8）和 1.2（0.6-2.1），GSTT10/0 为 1.8（1.1-3.0）和 2.2（1.1-4.4），而 GSTT11/1。在女性中，随着 GSTT1 拷贝数的减少，子宫体癌的累积发病率增加（趋势=0.04）。子宫体癌的 HRs 分别为 GSTT11/0 和 GSTT10/0 为 1.8（1.0-3.2）和 2.2（1.0-4.6），而 GSTT11/1。最后，随着 GSTM1 拷贝数的减少，膀胱癌的累积发病率增加，5 年生存率降低（P=0.03-0.05）。膀胱癌的 HRs 分别为 GSTM11/0 和 GSTM10/0 为 1.5（0.7-3.2）和 2.0（0.9-4.3），而 GSTM11/1。膀胱癌诊断后死亡的 HR 为 GSTM10/0 为 1.9（1.0-3.7），而 GSTM1*1/0。总之，GSTT1 和 GSTM1 的精确 CNV 可预测前列腺癌和膀胱癌以及子宫体癌的发病率和 5 年生存率。
