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

Ali Amin Al Olama; Sara Benlloch; Antonis C. Antoniou; Grahamg Giles; Gianluca Severi; David E. Neal; Fie C Hamdy; Jenny L. Donovan; Kenneth Muir; Johanna Schleutker; Brian E. Henderson; Christopher A. Haiman; Fredrick R. Schumacher; Nora Pashayan; Paul D.P. Pharoah; Elaine A. Ostrander; Janet L. Stanford; Jyotsna Batra; Judith A. Clements; Suzanne K. Chambers; Maren Weischer; Børge G. Nordestgaard; Sue A. Ingles; Karina D. Sorensen; T Murtola; Jong Y. Park; Cezary Cybulski; Christiane Maier; Thilo Doerk; Joanne L. Dickinson; Lisa Cannon-Albright; Hermann Brenner; Timothy R. Rebbeck; Charnita Zeigler-Johnson; Tomonori Habuchi; Stephen N. Thibodeau; Kathleen A. Cooney; Pierre O. Chappuis; Pierre Hutter; Radka P. Kaneva; William D. Foulkes; Maurice P. Zeegers; Yong Jie Lu; Hong Wei Zhang; Robert Stephenson; Angela Cox; Melissa C. Southey; Amanda B. Spurdle; Liesel Fitz Gerald; Daniel Leongamornlert; Edward Saunders; Malgorzata Tymrakiewicz; Michelle Guy; Tokhir Dadaev; Sarah J. Little; Koveela Govindasami; Emma Sawyer; Rosemary Wilkinson; Kathleen Herkommer; John L. Hopper; Aritaya Lophatonanon; Antje E. Rinckleb; Zsofia Kote-Jarai; Rosalind A. Eeles; Douglas F. Easton; Esther John; Amit Joshi; Ahva Shahabi; James R. Marthick; Mariana C. Stern; Roman Corral; David M.A. Wallace; R. I. Bhatt; K. Subramonian; John Arrand; Louise Flanagan; Sita Ann Bradley; Prasad Bollina; Sue Bonnington; Lynne Bradshaw; James Catto; Debbie Cooper; Liz Down; Andrew Doble; Alan Doherty; Garrett Durkan; Emma Elliott; David Gillatt; Pippa Herbert; Joanne Howson; Mandy Jones; Roger Kockelbergh; Rajeev Kumar; Peter Holding; Howard Kynaston; Athene Lane; Teresa Lennon; Norma Lyons; Hing Leung; Malcolm Mason; Hilary Moody; Philip Powell; Alan Paul; Stephen Prescott; Derek Rosario; Patricia O'Sullivan; Pauline Thompson; Sarah Tidball; Paul M. Brown; Anne George; Gemma Marsden; Michael Davis; Stephen Edwards; Cyril Fisher; Charles Jameson; Elizabeth Page; John Pedersen; Joanne Aitken; Robert A. Gardiner; Srilakshmi Srinivasan; Felicity Lose; Mary Anne Kedda; Kimberly Alexander; Tracy O'Mara; Gail Risbridger; Wayne Tilley; Lisa Horvarth; Peter Heathcote; Glenn Wood; Greg Malone; Hema Samaratunga; Pamela Saunders; Allison Eckert; Trina Yeadon; Kris Kerr; Angus Collins; Megan Turner; Simon J. Foote; Andrea Polanowski; Rebekah M. Mcwhirter; Terrence Dwyer; Christopher L. Blizzard; Elenko Popov; Darina Kachakova; Atanaska Mitkova; Teodora Goranova; Gergana Stancheva; Olga Beltcheva; Rumyana Dodova; Aleksandrina Vlahova; Tihomir Dikov; Svetlana Christova; Michael Borre; P Kujala; Sune F. Nielsen; Peter Iversen; Andreas Røder; Stig E. Bojesen; Aida Karina Dieffenbach; Manuel Luedeke; Mark Schrader; Josef Hoegel; Walther Vogel; Liisa Maattanen; Teuvo Tammela; Anssi Auvinen; Lori Tillmans; Shaun Riska; Liang Wang; Dan Stram; Kolonel Laurence; Julio Pow-Sang; Hyun Y. Park; Selina Radlein; Maria Rincon; Babu Zachariah

doi:10.1158/1055-9965.epi-14-0317

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

Ali Amin Al Olama, Sara Benlloch, Antonis C. Antoniou, Grahamg Giles, Gianluca Severi, David E. Neal, Fie C Hamdy, Jenny L. Donovan, Kenneth Muir, Johanna Schleutker, Brian E. Henderson, Christopher A. Haiman, Fredrick R. Schumacher, Nora Pashayan, Paul D.P. Pharoah, Elaine A. Ostrander, Janet L. Stanford, Jyotsna Batra, Judith A. Clements, Suzanne K. ChambersMaren Weischer, Børge G. Nordestgaard, Sue A. Ingles, Karina D. Sorensen, T Murtola, Jong Y. Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L. Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R. Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N. Thibodeau, Kathleen A. Cooney, Pierre O. Chappuis, Pierre Hutter, Radka P. Kaneva, William D. Foulkes, Maurice P. Zeegers, Yong Jie Lu, Hong Wei Zhang, Robert Stephenson, Angela Cox, Melissa C. Southey, Amanda B. Spurdle, Liesel Fitz Gerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J. Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L. Hopper, Aritaya Lophatonanon, Antje E. Rinckleb, Zsofia Kote-Jarai, Rosalind A. Eeles, Douglas F. Easton, Esther John, Amit Joshi, Ahva Shahabi, James R. Marthick, Mariana C. Stern, Roman Corral, David M.A. Wallace, R. I. Bhatt, K. Subramonian, John Arrand, Louise Flanagan, Sita Ann Bradley, Prasad Bollina, Sue Bonnington, Lynne Bradshaw, James Catto, Debbie Cooper, Liz Down, Andrew Doble, Alan Doherty, Garrett Durkan, Emma Elliott, David Gillatt, Pippa Herbert, Joanne Howson, Mandy Jones, Roger Kockelbergh, Rajeev Kumar, Peter Holding, Howard Kynaston, Athene Lane, Teresa Lennon, Norma Lyons, Hing Leung, Malcolm Mason, Hilary Moody, Philip Powell, Alan Paul, Stephen Prescott, Derek Rosario, Patricia O'Sullivan, Pauline Thompson, Sarah Tidball, Paul M. Brown, Anne George, Gemma Marsden, Michael Davis, Stephen Edwards, Cyril Fisher, Charles Jameson, Elizabeth Page, John Pedersen, Joanne Aitken, Robert A. Gardiner, Srilakshmi Srinivasan, Felicity Lose, Mary Anne Kedda, Kimberly Alexander, Tracy O'Mara, Gail Risbridger, Wayne Tilley, Lisa Horvarth, Peter Heathcote, Glenn Wood, Greg Malone, Hema Samaratunga, Pamela Saunders, Allison Eckert, Trina Yeadon, Kris Kerr, Angus Collins, Megan Turner, Simon J. Foote, Andrea Polanowski, Rebekah M. Mcwhirter, Terrence Dwyer, Christopher L. Blizzard, Elenko Popov, Darina Kachakova, Atanaska Mitkova, Teodora Goranova, Gergana Stancheva, Olga Beltcheva, Rumyana Dodova, Aleksandrina Vlahova, Tihomir Dikov, Svetlana Christova, Michael Borre, P Kujala, Sune F. Nielsen, Peter Iversen, Andreas Røder, Stig E. Bojesen, Aida Karina Dieffenbach, Manuel Luedeke, Mark Schrader, Josef Hoegel, Walther Vogel, Liisa Maattanen, Teuvo Tammela, Anssi Auvinen, Lori Tillmans, Shaun Riska, Liang Wang, Dan Stram, Kolonel Laurence, Julio Pow-Sang, Hyun Y. Park, Selina Radlein, Maria Rincon, Babu Zachariah

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

54 Sitaatiot (Scopus)

Abstrakti

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.

Alkuperäiskieli	Englanti
Sivut	1121-1129
Sivumäärä	9
Julkaisu	Cancer Epidemiology, Biomarkers & Prevention
Vuosikerta	24
Numero	7
DOI - pysyväislinkit	https://doi.org/10.1158/1055-9965.epi-14-0317
Tila	Julkaistu - 2015
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

Jufo-taso 2

YK:n kestävän kehityksen tavoitteet

Tämä tuotos edistää seuraavia kestävän kehityksen tavoitteita:

Pääsy asiakirjaan

10.1158/1055-9965.epi-14-0317

Siteeraa tätä

Al Olama, A. A., Benlloch, S., Antoniou, A. C., Giles, G., Severi, G., Neal, D. E., Hamdy, F. C., Donovan, J. L., Muir, K., Schleutker, J., Henderson, B. E., Haiman, C. A., Schumacher, F. R., Pashayan, N., Pharoah, P. D. P., Ostrander, E. A., Stanford, J. L., Batra, J., Clements, J. A., ... Zachariah, B. (2015). Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci. Cancer Epidemiology, Biomarkers & Prevention, 24(7), 1121-1129. https://doi.org/10.1158/1055-9965.epi-14-0317

@article{dcfcd8272a0e4a699b2c1824e5e42910,

title = "Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci",

abstract = "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.",

author = "{Al Olama}, {Ali Amin} and Sara Benlloch and Antoniou, {Antonis C.} and Grahamg Giles and Gianluca Severi and Neal, {David E.} and Hamdy, {Fie C} and Donovan, {Jenny L.} and Kenneth Muir and Johanna Schleutker and Henderson, {Brian E.} and Haiman, {Christopher A.} and Schumacher, {Fredrick R.} and Nora Pashayan and Pharoah, {Paul D.P.} and Ostrander, {Elaine A.} and Stanford, {Janet L.} and Jyotsna Batra and Clements, {Judith A.} and Chambers, {Suzanne K.} and Maren Weischer and Nordestgaard, {B{\o}rge G.} and Ingles, {Sue A.} and Sorensen, {Karina D.} and T Murtola and Park, {Jong Y.} and Cezary Cybulski and Christiane Maier and Thilo Doerk and Dickinson, {Joanne L.} and Lisa Cannon-Albright and Hermann Brenner and Rebbeck, {Timothy R.} and Charnita Zeigler-Johnson and Tomonori Habuchi and Thibodeau, {Stephen N.} and Cooney, {Kathleen A.} and Chappuis, {Pierre O.} and Pierre Hutter and Kaneva, {Radka P.} and Foulkes, {William D.} and Zeegers, {Maurice P.} and Lu, {Yong Jie} and Zhang, {Hong Wei} and Robert Stephenson and Angela Cox and Southey, {Melissa C.} and Spurdle, {Amanda B.} and Gerald, {Liesel Fitz} and Daniel Leongamornlert and Edward Saunders and Malgorzata Tymrakiewicz and Michelle Guy and Tokhir Dadaev and Little, {Sarah J.} and Koveela Govindasami and Emma Sawyer and Rosemary Wilkinson and Kathleen Herkommer and Hopper, {John L.} and Aritaya Lophatonanon and Rinckleb, {Antje E.} and Zsofia Kote-Jarai and Eeles, {Rosalind A.} and Easton, {Douglas F.} and Esther John and Amit Joshi and Ahva Shahabi and Marthick, {James R.} and Stern, {Mariana C.} and Roman Corral and Wallace, {David M.A.} and Bhatt, {R. I.} and K. Subramonian and John Arrand and Louise Flanagan and Bradley, {Sita Ann} and Prasad Bollina and Sue Bonnington and Lynne Bradshaw and James Catto and Debbie Cooper and Liz Down and Andrew Doble and Alan Doherty and Garrett Durkan and Emma Elliott and David Gillatt and Pippa Herbert and Joanne Howson and Mandy Jones and Roger Kockelbergh and Rajeev Kumar and Peter Holding and Howard Kynaston and Athene Lane and Teresa Lennon and Norma Lyons and Hing Leung and Malcolm Mason and Hilary Moody and Philip Powell and Alan Paul and Stephen Prescott and Derek Rosario and Patricia O'Sullivan and Pauline Thompson and Sarah Tidball and Brown, {Paul M.} and Anne George and Gemma Marsden and Michael Davis and Stephen Edwards and Cyril Fisher and Charles Jameson and Elizabeth Page and John Pedersen and Joanne Aitken and Gardiner, {Robert A.} and Srilakshmi Srinivasan and Felicity Lose and Kedda, {Mary Anne} and Kimberly Alexander and Tracy O'Mara and Gail Risbridger and Wayne Tilley and Lisa Horvarth and Peter Heathcote and Glenn Wood and Greg Malone and Hema Samaratunga and Pamela Saunders and Allison Eckert and Trina Yeadon and Kris Kerr and Angus Collins and Megan Turner and Foote, {Simon J.} and Andrea Polanowski and Mcwhirter, {Rebekah M.} and Terrence Dwyer and Blizzard, {Christopher L.} and Elenko Popov and Darina Kachakova and Atanaska Mitkova and Teodora Goranova and Gergana Stancheva and Olga Beltcheva and Rumyana Dodova and Aleksandrina Vlahova and Tihomir Dikov and Svetlana Christova and Michael Borre and P Kujala and Nielsen, {Sune F.} and Peter Iversen and Andreas R{\o}der and Bojesen, {Stig E.} and Dieffenbach, {Aida Karina} and Manuel Luedeke and Mark Schrader and Josef Hoegel and Walther Vogel and Liisa Maattanen and Teuvo Tammela and Anssi Auvinen and Lori Tillmans and Shaun Riska and Liang Wang and Dan Stram and Kolonel Laurence and Julio Pow-Sang and Park, {Hyun Y.} and Selina Radlein and Maria Rincon and Babu Zachariah",

year = "2015",

doi = "10.1158/1055-9965.epi-14-0317",

language = "English",

volume = "24",

pages = "1121--1129",

number = "7",

}

Al Olama, AA, Benlloch, S, Antoniou, AC, Giles, G, Severi, G, Neal, DE, Hamdy, FC, Donovan, JL, Muir, K, Schleutker, J, Henderson, BE, Haiman, CA, Schumacher, FR, Pashayan, N, Pharoah, PDP, Ostrander, EA, Stanford, JL, Batra, J, Clements, JA, Chambers, SK, Weischer, M, Nordestgaard, BG, Ingles, SA, Sorensen, KD, Murtola, T, Park, JY, Cybulski, C, Maier, C, Doerk, T, Dickinson, JL, Cannon-Albright, L, Brenner, H, Rebbeck, TR, Zeigler-Johnson, C, Habuchi, T, Thibodeau, SN, Cooney, KA, Chappuis, PO, Hutter, P, Kaneva, RP, Foulkes, WD, Zeegers, MP, Lu, YJ, Zhang, HW, Stephenson, R, Cox, A, Southey, MC, Spurdle, AB, Gerald, LF, Leongamornlert, D, Saunders, E, Tymrakiewicz, M, Guy, M, Dadaev, T, Little, SJ, Govindasami, K, Sawyer, E, Wilkinson, R, Herkommer, K, Hopper, JL, Lophatonanon, A, Rinckleb, AE, Kote-Jarai, Z, Eeles, RA, Easton, DF, John, E, Joshi, A, Shahabi, A, Marthick, JR, Stern, MC, Corral, R, Wallace, DMA, Bhatt, RI, Subramonian, K, Arrand, J, Flanagan, L, Bradley, SA, Bollina, P, Bonnington, S, Bradshaw, L, Catto, J, Cooper, D, Down, L, Doble, A, Doherty, A, Durkan, G, Elliott, E, Gillatt, D, Herbert, P, Howson, J, Jones, M, Kockelbergh, R, Kumar, R, Holding, P, Kynaston, H, Lane, A, Lennon, T, Lyons, N, Leung, H, Mason, M, Moody, H, Powell, P, Paul, A, Prescott, S, Rosario, D, O'Sullivan, P, Thompson, P, Tidball, S, Brown, PM, George, A, Marsden, G, Davis, M, Edwards, S, Fisher, C, Jameson, C, Page, E, Pedersen, J, Aitken, J, Gardiner, RA, Srinivasan, S, Lose, F, Kedda, MA, Alexander, K, O'Mara, T, Risbridger, G, Tilley, W, Horvarth, L, Heathcote, P, Wood, G, Malone, G, Samaratunga, H, Saunders, P, Eckert, A, Yeadon, T, Kerr, K, Collins, A, Turner, M, Foote, SJ, Polanowski, A, Mcwhirter, RM, Dwyer, T, Blizzard, CL, Popov, E, Kachakova, D, Mitkova, A, Goranova, T, Stancheva, G, Beltcheva, O, Dodova, R, Vlahova, A, Dikov, T, Christova, S, Borre, M, Kujala, P, Nielsen, SF, Iversen, P, Røder, A, Bojesen, SE, Dieffenbach, AK, Luedeke, M, Schrader, M, Hoegel, J, Vogel, W, Maattanen, L, Tammela, T , Auvinen, A, Tillmans, L, Riska, S, Wang, L, Stram, D, Laurence, K, Pow-Sang, J, Park, HY, Radlein, S, Rincon, M & Zachariah, B 2015, 'Risk analysis of prostate cancer in practical, a multinational consortium, using 25 known prostate cancer susceptibility loci', Cancer Epidemiology, Biomarkers & Prevention, Vuosikerta 24, Nro 7, Sivut 1121-1129. https://doi.org/10.1158/1055-9965.epi-14-0317

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, Fie 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 - Murtola, T

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 - Kujala, P

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

Y1 - 2015

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.

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

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

M3 - Article

AN - SCOPUS:84941788242

SN - 1055-9965

VL - 24

SP - 1121

EP - 1129

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 7

ER -

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

Abstrakti

Julkaisufoorumi-taso

YK:n kestävän kehityksen tavoitteet

Pääsy asiakirjaan

Sormenjälki

Siteeraa tätä