TUTCRIS Research Portal

TY - JOUR

T1 - Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Antoniou, Antonis C.

AU - Giles, Grahamg

AU - Severi, Gianluca

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - Donovan, Jenny L.

AU - Muir, Kenneth

AU - Schleutker, Johanna

AU - Henderson, Brian E.

AU - Haiman, Christopher A.

AU - Schumacher, Fredrick R.

AU - Pashayan, Nora

AU - Pharoah, Paul D.P.

AU - Ostrander, Elaine A.

AU - Stanford, Janet L.

AU - Batra, Jyotsna

AU - Clements, Judith A.

AU - Chambers, Suzanne K.

AU - Weischer, Maren

AU - Nordestgaard, Børge G.

AU - Ingles, Sue A.

AU - Sorensen, Karina D.

AU - Orntoft, Torben F.

AU - Park, Jong Y.

AU - Cybulski, Cezary

AU - Maier, Christiane

AU - Doerk, Thilo

AU - Dickinson, Joanne L.

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Rebbeck, Timothy R.

AU - Zeigler-Johnson, Charnita

AU - Habuchi, Tomonori

AU - Thibodeau, Stephen N.

AU - Cooney, Kathleen A.

AU - Chappuis, Pierre O.

AU - Hutter, Pierre

AU - Kaneva, Radka P.

AU - Foulkes, William D.

AU - Zeegers, Maurice P.

AU - Lu, Yong Jie

AU - Zhang, Hong Wei

AU - Stephenson, Robert

AU - Cox, Angela

AU - Southey, Melissa C.

AU - Spurdle, Amanda B.

AU - Gerald, Liesel Fitz

AU - Leongamornlert, Daniel

AU - Saunders, Edward

AU - Tymrakiewicz, Malgorzata

AU - Guy, Michelle

AU - Dadaev, Tokhir

AU - Little, Sarah J.

AU - Govindasami, Koveela

AU - Sawyer, Emma

AU - Wilkinson, Rosemary

AU - Herkommer, Kathleen

AU - Hopper, John L.

AU - Lophatonanon, Aritaya

AU - Rinckleb, Antje E.

AU - Kote-Jarai, Zsofia

AU - Eeles, Rosalind A.

AU - Easton, Douglas F.

AU - John, Esther

AU - Joshi, Amit

AU - Shahabi, Ahva

AU - Marthick, James R.

AU - Stern, Mariana C.

AU - Corral, Roman

AU - Wallace, David M.A.

AU - Bhatt, R. I.

AU - Subramonian, K.

AU - Arrand, John

AU - Flanagan, Louise

AU - Bradley, Sita Ann

AU - Bollina, Prasad

AU - Bonnington, Sue

AU - Bradshaw, Lynne

AU - Catto, James

AU - Cooper, Debbie

AU - Down, Liz

AU - Doble, Andrew

AU - Doherty, Alan

AU - Durkan, Garrett

AU - Elliott, Emma

AU - Gillatt, David

AU - Herbert, Pippa

AU - Howson, Joanne

AU - Jones, Mandy

AU - Kockelbergh, Roger

AU - Kumar, Rajeev

AU - Holding, Peter

AU - Kynaston, Howard

AU - Lane, Athene

AU - Lennon, Teresa

AU - Lyons, Norma

AU - Leung, Hing

AU - Mason, Malcolm

AU - Moody, Hilary

AU - Powell, Philip

AU - Paul, Alan

AU - Prescott, Stephen

AU - Rosario, Derek

AU - O'Sullivan, Patricia

AU - Thompson, Pauline

AU - Tidball, Sarah

AU - Brown, Paul M.

AU - George, Anne

AU - Marsden, Gemma

AU - Davis, Michael

AU - Edwards, Stephen

AU - Fisher, Cyril

AU - Jameson, Charles

AU - Page, Elizabeth

AU - Pedersen, John

AU - Aitken, Joanne

AU - Gardiner, Robert A.

AU - Srinivasan, Srilakshmi

AU - Lose, Felicity

AU - Kedda, Mary Anne

AU - Alexander, Kimberly

AU - O'Mara, Tracy

AU - Risbridger, Gail

AU - Tilley, Wayne

AU - Horvarth, Lisa

AU - Heathcote, Peter

AU - Wood, Glenn

AU - Malone, Greg

AU - Samaratunga, Hema

AU - Saunders, Pamela

AU - Eckert, Allison

AU - Yeadon, Trina

AU - Kerr, Kris

AU - Collins, Angus

AU - Turner, Megan

AU - Foote, Simon J.

AU - Polanowski, Andrea

AU - Mcwhirter, Rebekah M.

AU - Dwyer, Terrence

AU - Blizzard, Christopher L.

AU - Popov, Elenko

AU - Kachakova, Darina

AU - Mitkova, Atanaska

AU - Goranova, Teodora

AU - Stancheva, Gergana

AU - Beltcheva, Olga

AU - Dodova, Rumyana

AU - Vlahova, Aleksandrina

AU - Dikov, Tihomir

AU - Christova, Svetlana

AU - Borre, Michael

AU - Klarskov, Peter

AU - Nielsen, Sune F.

AU - Iversen, Peter

AU - Røder, Andreas

AU - Bojesen, Stig E.

AU - Dieffenbach, Aida Karina

AU - Luedeke, Manuel

AU - Schrader, Mark

AU - Hoegel, Josef

AU - Vogel, Walther

AU - Maattanen, Liisa

AU - Tammela, Teuvo

AU - Auvinen, Anssi

AU - Tillmans, Lori

AU - Riska, Shaun

AU - Wang, Liang

AU - Stram, Dan

AU - Laurence, Kolonel

AU - Pow-Sang, Julio

AU - Park, Hyun Y.

AU - Radlein, Selina

AU - Rincon, Maria

AU - Zachariah, Babu

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

AB - Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

UR - http://www.scopus.com/inward/record.url?scp=84941788242&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-14-0317

DO - 10.1158/1055-9965.EPI-14-0317

M3 - Article

VL - 24

SP - 1121

EP - 1129

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 7

ER -