Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.
Abstact
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
Authors
- Albanes D
- Aldrich MC
- Aly M
- Andriole GL
- Aukim-Hastie C
- Auvinen A
- Barnett G
- Batra J
- Benlloch S
- Bensen JT
- Berndt SI
- Blanchet P
- Blot WJ
- Bojesen SE
- Borre M
- Brandão A
- Brenner H
- Brook MN
- Brureau L
- Burnet N
- Bush WS
- Cancel-Tassin G
- Cannon-Albright L
- Carpten J
- Carter BD
- Casey G
- Castaño-Vinyals G
- Castelao JE
- Chambers S
- Chanock SJ
- Chou A
- Claessens F
- Clements JA
- Conti DV
- Cook MB
- Crawford DC
- Cuk K
- Cullen JC
- Cussenot O
- Cybulski C
- Dadaev T
- Darst BF
- De Meerleer G
- De Ruyck K
- Ding YC
- Donovan JL
- Drake BF
- Dunning AM
- Easton DF
- Eeles RA
- Eklund M
- Fachal L
- Feng N
- Finelli A
- Fleshner NE
- Fontham ETH
- Fowke JH
- Freeman LEB
- Fujita M
- Gago-Dominguez M
- Gamulin M
- Gapstur SM
- Geybels MS
- Ghoussaini M
- Giles GG
- Giovannucci E
- Goodman PJ
- Grindedal EM
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- Hamdy FC
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- Hennis AJM
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- Huff CD
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- Ingles SA
- Isaacs WB
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- John EM
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- Kaneva R
- Kerns SL
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- Khaw KT
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