Copy number variation in glutathione-S-transferase T1 and M1 predicts incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer in the general population.
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 GSTT1*1/0, and 1.8 (1.1-3.0) and 2.2 (1.1-4.4) for GSTT1*0/0 versus GSTT1*1/1. 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 GSTT1*1/0 and GSTT1*0/0 versus GSTT1*1/1. 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 GSTM1*1/0 and GSTM1*0/0 versus GSTM1*1/1. The HR for death after bladder cancer diagnosis was 1.9 (1.0-3.7) for GSTM1*0/0 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.
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
M S
MS
Nørskov
R
R
Frikke-Schmidt
S E
SE
Bojesen
B G
BG
Nordestgaard
S
S
Loft
A
A
Tybjærg-Hansen
D000328:Adult; D016009:Chi-Square Distribution; D056915:DNA Copy Number Variations; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D014594:Uterine Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1