TY - JOUR
T1 - Prostate cancer (PCa) risk variants and risk of fatal PCa in the national cancer institute breast and prostate cancer cohort consortium
AU - Shui, Irene M.
AU - Lindström, Sara
AU - Kibel, Adam S.
AU - Berndt, Sonja I.
AU - Campa, Daniele
AU - Gerke, Travis
AU - Penney, Kathryn L.
AU - Albanes, Demetrius
AU - Berg, Christine
AU - Bueno-De-Mesquita, H. Bas
AU - Chanock, Stephen
AU - Crawford, E. David
AU - Diver, W. Ryan
AU - Gapstur, Susan M.
AU - Gaziano, J. Michael
AU - Giles, Graham G.
AU - Henderson, Brian
AU - Hoover, Robert
AU - Johansson, Mattias
AU - Le Marchand, Loic
AU - Ma, Jing
AU - Navarro, Carmen
AU - Overvad, Kim
AU - Schumacher, Fredrick R.
AU - Severi, Gianluca
AU - Siddiq, Afshan
AU - Stampfer, Meir
AU - Stevens, Victoria L.
AU - Travis, Ruth C.
AU - Trichopoulos, Dimitrios
AU - Vineis, Paolo
AU - Mucci, Lorelei A.
AU - Yeager, Meredith
AU - Giovannucci, Edward
AU - Kraft, Peter
N1 - Funding Information:
Funding/Support and role of the sponsor: This work was supported by the NIH NCI (cooperative agreement U19 CA148537-01). The maintenance of the Cancer Prevention Study II is supported by the American Cancer Society, and genotyping of the CPS-II samples was supported by a grant from the NCI (5U01CA098710). The Danish study Diet, Cancer and Health was funded by the Danish Cancer Society. EPIC-Greece was supported through the Hellenic Health Foundation. EPIC-Spain was supported by Health Research Fund; the regional governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236), and Navarra; and ISCIII RETIC (RD06/0020; Spain). PLCO was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, NCI. The Melbourne Collaborative Cohort Study recruitment was funded and its follow-up supported by Cancer Council Victoria.
Funding Information:
Financial disclosures: Irene M. Shui certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Drs. Shui and Gerke were supported by a National Research Service Award (T32 CA09001) from the US National Institutes of Health (NIH) National Cancer Institute (NCI). Dr. Shui also received a US Army Department of Defense Prostate Cancer Postdoctoral Fellowship. Drs. Penney and Mucci were supported by the Prostate Cancer Foundation.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Genetic epidemiology
KW - Prostate cancer
KW - Prostate cancer mortality
KW - Risk single nucleotide polymorphisms
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U2 - 10.1016/j.eururo.2013.12.058
DO - 10.1016/j.eururo.2013.12.058
M3 - Article
C2 - 24411283
AN - SCOPUS:84899529644
SN - 0302-2838
VL - 65
SP - 1069
EP - 1075
JO - European Urology
JF - European Urology
IS - 6
ER -