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Reply to “Variation in KLK genes, prostate-specific antigen and risk of prostate cancer”

Nature Genetics volume 40, pages 1035–1036 (2008)Cite this article

Eeles et al . reply:

We recently conducted a genome-wide association study (GWAS) using data from 1,854 individuals with clinically detected (not PSA screened) prostate cancer diagnosed at <60 years or with a family history of the disease, and 1,894 population-screened controls with a prostate-specific antigen (PSA) of <0.5ng/ml (ref. 1). These were analyzed for 541,129 SNPs using the Illumina Infinium platform. We then evaluated putative associations using a further 3,268 cases and 3,366 controls. After these two stages, associations at seven loci, on chromosomes 3,6,7,10,11,19 and X, reached genome-wide levels of significance (P = 2.7 × 10−8 to P = 8.7 × 10−29). The SNP rs2735839 on chromosome 19 lies between two kallikreins, PSA (encoded by KLK3) and hK2 (encoded by KLK2). It was associated with a per allele OR for prostate cancer of 0.83 (95% CI = 0.75–0.91; Ptrend in stage 2 = 0.0002; Ptrend overall = 2 × 10−18). We also showed that rs2735839 was strongly associated with PSA level, in the direction consistent with the disease association (per allele rise in geometric mean PSA = 1.12., P = 6 × 10−8).

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Figure 1: Forest plot giving the per-allele odds ratios between rs2735839 and prostate cancer for each study in PRACTICAL.

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Acknowledgements

This work was supported by Cancer Research UK Grant C5047/A3354. D.F.E. is a Principal Research Fellow of Cancer Research UK. We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK, grants from the National Health and Medical Research Council, Australia (209057, 251533, 450104), VicHealth, The Cancer Council Victoria, The Whitten Foundation and Tattersall's. The ProtecT study is ongoing and is funded by the Health Technology Assessment Programme (projects 96/20/06, 96/20/99). The ProtecT trial and its linked ProMPT and CAP (Comparison Arm for ProtecT) studies are supported by Department of Health, England, Cancer Research UK grant number C522/A8649, Medical Research Council of England grant number G0500966, ID 75466 and The NCRI, UK. The epidemiological data for ProtecT were generated though funding from the Southwest National Health Service Research and Development. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of Health of England.

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Authors and Affiliations

  1. Translational Cancer Genetics Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, Surrey, UK

    Rosalind Eeles

  2. The Royal Marsden Hospital NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, Surrey, UK

    Rosalind Eeles

  3. Cancer Epidemiology Centre, The Cancer Council Victoria, 1 Rathdowne Street, Carlton, VIC 3053, Australia

    Graham Giles

  4. Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, 723 Swanston Street, Carlton, VIC 3053, Australia

    Graham Giles

  5. Departments of Oncology and Surgery, Surgical Oncology (Uro-Oncology S4), University of Cambridge, Box 279, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    David Neal

  6. Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK

    David Neal

  7. University of Nottingham Medical School, Queens Medical Centre, Nottingham, NG7 2UH, UK

    Kenneth Muir

  8. Cancer Research UK Genetic Epidemiology Unit, University of Cambridge Strangeways Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK

    Douglas F Easton

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Competing interests

S. Machtens, a member of PRACTICAL, has received Bard, Pfizer, Sanofi–Aventis Speakers Bureau/Honoraria. R. Eeles has received educational grants from Tepnel Life Sciences and Illumina. In our opinion this does not influence the content of the paper.

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Eeles, R., Giles, G., Neal, D. et al. Reply to “Variation in KLK genes, prostate-specific antigen and risk of prostate cancer”. Nat Genet 40, 1035–1036 (2008). https://doi.org/10.1038/ng0908-1035

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