University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Matejcic, Marco, Saunders, Edward J, Dadaev, Tokhir, Brook, Mark N, Wang, Kan, Sheng, Xin, Al Olama, Ali Amin, Schumacher, Fredrick R, Ingles, Sue A, Govindasami, Koveela , Benlloch, Sara, Berndt, Sonja I, Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L, Gapstur, Susan M, Tangen, Catherine M, Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D, Maehle, Lovise, Grindedal, Eli M, Strom, Sara S, Neal, David E, Hamdy, Freddie C, Donovan, Jenny L, Travis, Ruth C, Hamilton, Robert J, Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G, Kibel, Adam S, Vega, Ana, Bensen, Jeanette T, Kogevinas, Manolis, Penney, Kathryn L, Park, Jong Y, Stanford, Janet L, Cybulski, Cezary, Nordestgaard, Børge G, Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R, Neuhausen, Susan L, De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F, Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A, Dominguez, Manuela G, Roobol, Monique J, Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A, Pandha, Hardev, Thibodeau, Stephen N, Schaid, Daniel J, Wiklund, Fredrik, Chanock, Stephen J, Easton, Douglas F, Eeles, Rosalind A, Kote-Jarai, Zsofia, Conti, David V and Haiman, Christopher A (2018) Germline variation at 8q24 and prostate cancer risk in men of European ancestry Nature Communications, 9, 4616.

[img]
Preview
Text
Germline variation at 8q24.pdf - Version of Record
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p<4.28x10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI=3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Matejcic, Marco
Saunders, Edward J
Dadaev, Tokhir
Brook, Mark N
Wang, Kan
Sheng, Xin
Al Olama, Ali Amin
Schumacher, Fredrick R
Ingles, Sue A
Govindasami, Koveela
Benlloch, Sara
Berndt, Sonja I
Albanes, Demetrius
Koutros, Stella
Muir, Kenneth
Stevens, Victoria L
Gapstur, Susan M
Tangen, Catherine M
Batra, Jyotsna
Clements, Judith
Gronberg, Henrik
Pashayan, Nora
Schleutker, Johanna
Wolk, Alicja
West, Catharine
Mucci, Lorelei
Kraft, Peter
Cancel-Tassin, Géraldine
Sorensen, Karina D
Maehle, Lovise
Grindedal, Eli M
Strom, Sara S
Neal, David E
Hamdy, Freddie C
Donovan, Jenny L
Travis, Ruth C
Hamilton, Robert J
Rosenstein, Barry
Lu, Yong-Jie
Giles, Graham G
Kibel, Adam S
Vega, Ana
Bensen, Jeanette T
Kogevinas, Manolis
Penney, Kathryn L
Park, Jong Y
Stanford, Janet L
Cybulski, Cezary
Nordestgaard, Børge G
Brenner, Hermann
Maier, Christiane
Kim, Jeri
Teixeira, Manuel R
Neuhausen, Susan L
De Ruyck, Kim
Razack, Azad
Newcomb, Lisa F
Lessel, Davor
Kaneva, Radka
Usmani, Nawaid
Claessens, Frank
Townsend, Paul A
Dominguez, Manuela G
Roobol, Monique J
Menegaux, Florence
Khaw, Kay-Tee
Cannon-Albright, Lisa A
Pandha, HardevH.Pandha@surrey.ac.uk
Thibodeau, Stephen N
Schaid, Daniel J
Wiklund, Fredrik
Chanock, Stephen J
Easton, Douglas F
Eeles, Rosalind A
Kote-Jarai, Zsofia
Conti, David V
Haiman, Christopher A
Date : 5 November 2018
DOI : 10.1038/s41467-018-06863-1
Copyright Disclaimer : © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Contributors :
ContributionNameEmailORCID
http://www.loc.gov/loc.terms/relators/CTBThe PRACTICAL Consortium,
Additional Information : An Author Correction to this article was published on 17 January 2019. See https://www.nature.com/articles/s41467-019-08293-z for details.
Depositing User : Melanie Hughes
Date Deposited : 14 Nov 2018 12:10
Last Modified : 21 Jan 2019 10:57
URI: http://epubs.surrey.ac.uk/id/eprint/849875

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800