Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
Eeles RA., Olama AAA., Benlloch S., Saunders EJ., Leongamornlert DA., Tymrakiewicz M., Ghoussaini M., Luccarini C., Dennis J., Jugurnauth-Little S., Dadaev T., Neal DE., Hamdy FC., Donovan JL., Muir K., Giles GG., Severi G., Wiklund F., Gronberg H., Haiman CA., Schumacher F., Henderson BE., Le Marchand L., Lindstrom S., Kraft P., Hunter DJ., Gapstur S., Chanock SJ., Berndt SI., Albanes D., Andriole G., Schleutker J., Weischer M., Canzian F., Riboli E., Key TJ., Travis RC., Campa D., Ingles SA., John EM., Hayes RB., Pharoah PDP., Pashayan N., Khaw K-T., Stanford JL., Ostrander EA., Signorello LB., Thibodeau SN., Schaid D., Maier C., Vogel W., Kibel AS., Cybulski C., Lubinski J., Cannon-Albright L., Brenner H., Park JY., Kaneva R., Batra J., Spurdle AB., Clements JA., Teixeira MR., Dicks E., Lee A., Dunning AM., Baynes C., Conroy D., Maranian MJ., Ahmed S., Govindasami K., Guy M., Wilkinson RA., Sawyer EJ., Morgan A., Dearnaley DP., Horwich A., Huddart RA., Khoo VS., Parker CC., Van As NJ., Woodhouse CJ., Thompson A., Dudderidge T., Ogden C., Cooper CS., Lophatananon A., Cox A., Southey MC., Hopper JL., English DR., Aly M., Adolfsson J., Xu J., Zheng SL., Yeager M., Kaaks R., Diver WR., Gaudet MM., Stern MC., Corral R., Joshi AD., Shahabi A., Wahlfors T., Tammela TLJ., Auvinen A., Virtamo J., Klarskov P., Nordestgaard BG., Røder MA., Nielsen SF., Bojesen SE., Siddiq A., Fitzgerald LM., Kolb S., Kwon EM., Karyadi DM., Blot WJ., Zheng W., Cai Q., McDonnell SK., Rinckleb AE., Drake B., Colditz G., Wokolorczyk D., Stephenson RA., Teerlink C., Muller H., Rothenbacher D., Sellers TA., Lin H-Y., Slavov C., Mitev V., Lose F., Srinivasan S., Maia S., Paulo P., Lange E., Cooney KA., Antoniou AC., Vincent D., Bacot F., Tessier DC., COGS–Cancer Research UK GWAS–ELLIPSE (part of GAME-ON) Initiative None., Australian Prostate Cancer Bioresource None., UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology None., UK ProtecT (Prostate testing for cancer and Treatment) Study Collaborators None., PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium None., Kote-Jarai Z., Easton DF.
Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.