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

Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Kan Wang, Xin Sheng, Ali Amin Al Olama, Fredrick Schumacher, Sue A. Ingles, Koveela Govindasami, Sara Benlloch, Sonja Berndt, Demetrius Albanes, Stella Koutros, Kenneth Muir, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith Clements & 7 others PRACTICAL Consortium, Graham Giles, Roger L. Milne, Renea Taylor, Melissa M. Papargiris, Gail Risbridger, Melissa C. Southey

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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 < 4.28 × 10−15), 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.
Original languageEnglish
Article number382
Number of pages11
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 5 Nov 2018

Keywords

  • biochemistry
  • cancer
  • computational biology and bioinformatics
  • diseases
  • genetics

Cite this

Matejcic, Marco ; Saunders, Edward J. ; Dadaev, Tokhir ; Brook, Mark N. ; Wang, Kan ; Sheng, Xin ; Al Olama, Ali Amin ; Schumacher, Fredrick ; Ingles, Sue A. ; Govindasami, Koveela ; Benlloch, Sara ; Berndt, Sonja ; Albanes, Demetrius ; Koutros, Stella ; Muir, Kenneth ; Stevens, Victoria L. ; Gapstur, Susan M. ; Tangen, Catherine M. ; Batra, Jyotsna ; Clements, Judith ; PRACTICAL Consortium ; Giles, Graham ; Milne, Roger L. ; Taylor, Renea ; Papargiris, Melissa M. ; Risbridger, Gail ; Southey, Melissa C. / Germline variation at 8q24 and prostate cancer risk in men of European ancestry. In: Nature Communications. 2018 ; Vol. 9.
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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 < 4.28 × 10−15), 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.",
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author = "Marco Matejcic and Saunders, {Edward J.} and Tokhir Dadaev and Brook, {Mark N.} and Kan Wang and Xin Sheng and {Al Olama}, {Ali Amin} and Fredrick Schumacher and Ingles, {Sue A.} and Koveela Govindasami and Sara Benlloch and Sonja Berndt and Demetrius Albanes and Stella Koutros and Kenneth Muir and Stevens, {Victoria L.} and Gapstur, {Susan M.} and Tangen, {Catherine M.} and Jyotsna Batra and Judith Clements and {PRACTICAL Consortium} and Graham Giles and Milne, {Roger L.} and Renea Taylor and Papargiris, {Melissa M.} and Gail Risbridger and Southey, {Melissa C.}",
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Matejcic, M, Saunders, EJ, Dadaev, T, Brook, MN, Wang, K, Sheng, X, Al Olama, AA, Schumacher, F, Ingles, SA, Govindasami, K, Benlloch, S, Berndt, S, Albanes, D, Koutros, S, Muir, K, Stevens, VL, Gapstur, SM, Tangen, CM, Batra, J, Clements, J, PRACTICAL Consortium, Giles, G, Milne, RL, Taylor, R, Papargiris, MM, Risbridger, G & Southey, MC 2018, 'Germline variation at 8q24 and prostate cancer risk in men of European ancestry', Nature Communications, vol. 9, 382. https://doi.org/10.1038/s41467-018-06863-1

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; Ingles, Sue A.; Govindasami, Koveela; Benlloch, Sara; Berndt, Sonja; Albanes, Demetrius; Koutros, Stella; Muir, Kenneth; Stevens, Victoria L.; Gapstur, Susan M.; Tangen, Catherine M.; Batra, Jyotsna; Clements, Judith; PRACTICAL Consortium ; Giles, Graham; Milne, Roger L.; Taylor, Renea ; Papargiris, Melissa M.; Risbridger, Gail; Southey, Melissa C.

In: Nature Communications, Vol. 9, 382, 05.11.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Germline variation at 8q24 and prostate cancer risk in men of European ancestry

AU - Matejcic, Marco

AU - Saunders, Edward J.

AU - Dadaev, Tokhir

AU - Brook, Mark N.

AU - Wang, Kan

AU - Sheng, Xin

AU - Al Olama, Ali Amin

AU - Schumacher, Fredrick

AU - Ingles, Sue A.

AU - Govindasami, Koveela

AU - Benlloch, Sara

AU - Berndt, Sonja

AU - Albanes, Demetrius

AU - Koutros, Stella

AU - Muir, Kenneth

AU - Stevens, Victoria L.

AU - Gapstur, Susan M.

AU - Tangen, Catherine M.

AU - Batra, Jyotsna

AU - Clements, Judith

AU - PRACTICAL Consortium

AU - Giles, Graham

AU - Milne, Roger L.

AU - Taylor, Renea

AU - Papargiris, Melissa M.

AU - Risbridger, Gail

AU - Southey, Melissa C.

PY - 2018/11/5

Y1 - 2018/11/5

N2 - 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 < 4.28 × 10−15), 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.

AB - 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 < 4.28 × 10−15), 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.

KW - biochemistry

KW - cancer

KW - computational biology and bioinformatics

KW - diseases

KW - genetics

U2 - 10.1038/s41467-018-06863-1

DO - 10.1038/s41467-018-06863-1

M3 - Article

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 382

ER -