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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

The Pharmacogenomics Journal volume 11, pages 292–299 (2011)Cite this article

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Abstract

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.

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Acknowledgements

We thank Mette Refstrup for persistent attention to the details of the large-scale genotyping. We are indebted to the staff and the participants of The Copenhagen City Heart Study for important contributions. Sources of support: Center of Excellence ‘Air Pollution in a Life Time Health Perspective (AIRPOLIFE)’ from the Danish Research Agency, The Danish Medical Research Council, Ingeborg and Leo Dannin's Grant, and the Research Fund at Rigshospitalet, Copenhagen University Hospital.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    M S Nørskov, R Frikke-Schmidt & A Tybjærg-Hansen

  2. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    S E Bojesen & B G Nordestgaard

  3. The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    S E Bojesen, B G Nordestgaard & A Tybjærg-Hansen

  4. Department of Public Health, Faculty of Health Sciences, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark

    S Loft

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  1. M S Nørskov
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Correspondence to A Tybjærg-Hansen.

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Nørskov, M., Frikke-Schmidt, R., Bojesen, S. et al. 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. Pharmacogenomics J 11, 292–299 (2011). https://doi.org/10.1038/tpj.2010.38

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