Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Irene M Shui¹, Sara Lindström², Adam S Kibel³, Sonja I Berndt⁴, Daniele Campa⁵, Travis Gerke², Kathryn L Penney⁶, Demetrius Albanes⁴, Christine Berg⁷, H Bas Bueno-de-Mesquita⁸, Stephen Chanock⁹, E David Crawford¹⁰, W Ryan Diver¹¹, Susan M Gapstur¹¹, J Michael Gaziano¹², Graham G Giles¹³, Brian Henderson¹⁴, Robert Hoover⁴, Mattias Johansson¹⁵, Loic Le Marchand¹⁶, Jing Ma⁶, Carmen Navarro¹⁷, Kim Overvad¹⁸, Fredrick R Schumacher¹⁴, Gianluca Severi¹⁹, Afshan Siddiq²⁰, Meir Stampfer⁶, Victoria L Stevens¹¹, Ruth C Travis²¹, Dimitrios Trichopoulos²², Paolo Vineis²³, Lorelei A Mucci², Meredith Yeager⁹, Edward Giovannucci², Peter Kraft²

Affiliations

¹ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Electronic address: ishui@hsph.harvard.edu.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
³ Department of Surgery, Division of Urology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁵ Genomic Epidemiology Group, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany.
⁶ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA.
⁸ National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College London, London, United Kingdom.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA.
¹⁰ Urologic Oncology, University of Colorado, Denver, CO, USA.
¹¹ Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
¹² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Aging, Brigham and Women's Hospital, Boston, MA, USA.
¹³ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
¹⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁵ International Agency for Research on Cancer, Lyon, France; Department of Biobank Research, Umeå University, Umeå, Sweden.
¹⁶ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
¹⁷ Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain; Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
¹⁸ Department of Public Health, Aarhus University, Aarhus, Denmark.
¹⁹ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; HuGeF Foundation, Torino, Italy.
²⁰ Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
²¹ Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
²² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Hellenic Health Foundation, Athens, Greece.
²³ HuGeF Foundation, Torino, Italy; School of Public Health, Imperial College London, London, United Kingdom.

PMID: 24411283
PMCID: PMC4006298
DOI: 10.1016/j.eururo.2013.12.058

Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Irene M Shui et al. Eur Urol. 2014 Jun.

. 2014 Jun;65(6):1069-75.

doi: 10.1016/j.eururo.2013.12.058. Epub 2014 Jan 4.

Authors

Affiliations

¹ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Electronic address: ishui@hsph.harvard.edu.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
³ Department of Surgery, Division of Urology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁵ Genomic Epidemiology Group, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany.
⁶ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA.
⁸ National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College London, London, United Kingdom.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA.
¹⁰ Urologic Oncology, University of Colorado, Denver, CO, USA.
¹¹ Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
¹² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Aging, Brigham and Women's Hospital, Boston, MA, USA.
¹³ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
¹⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁵ International Agency for Research on Cancer, Lyon, France; Department of Biobank Research, Umeå University, Umeå, Sweden.
¹⁶ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
¹⁷ Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain; Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
¹⁸ Department of Public Health, Aarhus University, Aarhus, Denmark.
¹⁹ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; HuGeF Foundation, Torino, Italy.
²⁰ Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
²¹ Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
²² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Hellenic Health Foundation, Athens, Greece.
²³ HuGeF Foundation, Torino, Italy; School of Public Health, Imperial College London, London, United Kingdom.

PMID: 24411283
PMCID: PMC4006298
DOI: 10.1016/j.eururo.2013.12.058

Abstract

Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM).

Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.

Design, setting, and participants: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.

Outcome measurements and statistical analysis: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls.

Results and limitations: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p<0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p<0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only.

Conclusions: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa.

Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.

Keywords: Genetic epidemiology; Prostate cancer; Prostate cancer mortality; Risk single nucleotide polymorphisms.

PubMed Disclaimer

Comment in

Genetic variants in predicting aggressive prostate cancer: "ready for prime time?".
Vidal AC, Freedland SJ. Vidal AC, et al. Eur Urol. 2014 Jun;65(6):1076-7. doi: 10.1016/j.eururo.2014.01.025. Epub 2014 Jan 30. Eur Urol. 2014. PMID: 24507781 No abstract available.

References

1. Eeles RA, Olama AA, Benlloch S, et al. COGS–Cancer Research UK GWAS–ELLIPSE (part of GAME-ON) Initiative; Australian Prostate Cancer Bioresource; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons’ Section of Oncology; UK ProtecT (Prostate testing for cancer and Treatment) Study Collaborators; PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013;45:385–391. - PMC - PubMed
1. Epstein MM, Edgren G, Rider JR, Mucci LA, Adami HO. Temporal trends in cause of death among Swedish and US men with prostate cancer. J Natl Cancer Inst. 2012;104:1335–1342. - PMC - PubMed
1. Penney KL, Salinas CA, Pomerantz M, et al. Evaluation of 8q24 and 17q risk loci and prostate cancer mortality. Clin Cancer Res. 2009;15:3223–3230. - PMC - PubMed
1. Wiklund FE, Adami HO, Zheng SL, et al. Established prostate cancer susceptibility variants are not associated with disease outcome. Cancer Epidemiol Biomarkers Prev. 2009;18:1659–1662. - PMC - PubMed
1. Gallagher DJ, Vijai J, Cronin AM, et al. Susceptibility loci associated with prostate cancer progression and mortality. Clin Cancer Res. 2010;16:2819–2832. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Affiliations

Prostate cancer (PCa) risk variants and risk of fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Authors

Affiliations

Abstract

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous