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Clinical Research

Replication of a genetic variant for prostate cancer-specific mortality

Prostate Cancer and Prostatic Diseases volume 18, pages 260–263 (2015)Cite this article

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Abstract

Background:

Few genetic variants have been confirmed as being associated with prostate cancer-specific mortality (PCSM). A recent study identified 22 candidate single-nucleotide polymorphisms (SNPs) associated with PCSM in a Seattle-based patient cohort. Five of these associations were replicated in an independent Swedish cohort.

Methods:

We genotyped these 22 SNPs in Physicians’ Health Study (PHS) participants diagnosed with prostate cancer (PCa). Using the same model that was found to be most significant in the Seattle cohort, we examined the association of these SNPs with lethal disease with Cox proportional hazards models.

Results:

One SNP, rs5993891 in the ARVCF gene on chromosome 22q11, which had also replicated in the Swedish cohort, was also significantly associated with PCSM in the PHS cohort (hazard ratio (HR)=0.32; P=0.01). When we tested this SNP in an additional cohort (Health Professionals Follow-up Study, HPFS), the association was null (HR=0.95, P=0.90); however, a meta-analysis across all studies showed a statistically significant association with a HR of 0.52 (0.29–0.93, P=0.03).

Conclusions:

The association of rs5993891 with PCSM was further replicated in PHS and remains significant in a meta-analysis, though there was no association in HPFS. This SNP may contribute to a genetic panel of SNPs to determine at diagnosis whether a patient is more likely to exhibit an indolent or aggressive form of PCa. This study also emphasizes the importance of multiple rounds of replication.

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Acknowledgements

We are grateful to the participants and staff of the Physicians’ Health Study and Health Professionals Follow-up Study for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. This work was supported by the Prostate Cancer Foundation. The Physicians’ Health Study was supported by grants CA34944, CA40360 and CA097193 from the National Cancer Institute and HL26490 and HL34595 from the National Heart, Lung and Blood Institute. The Health Professionals Follow-up Study was supported by grants R01CA133891, R01CA141298-02 and P01CA055075. KLP is supported by a Prostate Cancer Foundation Young Investigator Award. IMS is supported by a US Army Department of Defense Prostate Cancer Research Program Post-doctoral Fellowship.

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Authors and Affiliations

  1. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    K L Penney & M J Stampfer

  2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    K L Penney, I M Shui, H D Sesso & M J Stampfer

  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    I M Shui & J L Stanford

  4. Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA

    Z Feng

  5. Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    H D Sesso

  6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    M J Stampfer

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  1. K L Penney
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  2. I M Shui
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  3. Z Feng
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Corresponding author

Correspondence to K L Penney.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

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Penney, K., Shui, I., Feng, Z. et al. Replication of a genetic variant for prostate cancer-specific mortality. Prostate Cancer Prostatic Dis 18, 260–263 (2015). https://doi.org/10.1038/pcan.2015.18

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