BACKGROUND: Men of African-ancestry have elevated prostate cancer (PCa) incidence and mortality compared to men of other racial groups. There is support for a genetic contribution to this disparity, with evidence of genetic heterogeneity in the underlying risk alleles between populations. Studies of PCa among African men may inform the contribution of genetic risk factors to the elevated disease burden in this population. METHODS: We conducted an association study of >100 previously reported PCa risk alleles among 571 incidence cases and 485 controls among Uganda men. Unconditional logistic regression was used to test genetic associations and a polygenic risk score (PRS) was derived to assess the cumulative effect of the known risk alleles in association with PCa risk. In an exploratory analysis, we also tested associations of 17 125 421 genotyped and imputed markers genome-wide in association with PCa risk. RESULTS: Of the 111 known risk loci with a frequency >1%, 75 (68%) had effects that were directionally consistent with the initial discovery population,14 (13%) of which were nominally significantly associated with PCa risk at P < 0.05. Compared to men with average risk (25th -75th percentile in PRS distribution), Ugandan men in the top 10% of the PRS, constructed of alleles outside of 8q24, had a 2.9-fold (95%CI: 1.75, 4.97) risk of developing PCa; risk for the top 10% increased to 4.86 (95%CI: 2.70, 8.76) with the inclusion of risk alleles at 8q24. In genome-wide association testing, the strongest associations were noted with known risk alleles located in the 8q24 region, including rs72725854 (OR = 3.37, P = 2.14 × 10-11 ) that is limited to populations of African ancestry (6% frequency). CONCLUSIONS: The ∼100 known PCa risk variants were shown to effectively stratify PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The 8q24 risk region was also found to be a major contributor to PCa risk in Ugandan men, with the African ancestry-specific risk variant rs72725854 estimated to account for 12% of PCa in this population.
BACKGROUND:Men of African-ancestry have elevated prostate cancer (PCa) incidence and mortality compared to men of other racial groups. There is support for a genetic contribution to this disparity, with evidence of genetic heterogeneity in the underlying risk alleles between populations. Studies of PCa among African men may inform the contribution of genetic risk factors to the elevated disease burden in this population. METHODS: We conducted an association study of >100 previously reported PCa risk alleles among 571 incidence cases and 485 controls among Uganda men. Unconditional logistic regression was used to test genetic associations and a polygenic risk score (PRS) was derived to assess the cumulative effect of the known risk alleles in association with PCa risk. In an exploratory analysis, we also tested associations of 17 125 421 genotyped and imputed markers genome-wide in association with PCa risk. RESULTS: Of the 111 known risk loci with a frequency >1%, 75 (68%) had effects that were directionally consistent with the initial discovery population,14 (13%) of which were nominally significantly associated with PCa risk at P < 0.05. Compared to men with average risk (25th -75th percentile in PRS distribution), Ugandan men in the top 10% of the PRS, constructed of alleles outside of 8q24, had a 2.9-fold (95%CI: 1.75, 4.97) risk of developing PCa; risk for the top 10% increased to 4.86 (95%CI: 2.70, 8.76) with the inclusion of risk alleles at 8q24. In genome-wide association testing, the strongest associations were noted with known risk alleles located in the 8q24 region, including rs72725854 (OR = 3.37, P = 2.14 × 10-11 ) that is limited to populations of African ancestry (6% frequency). CONCLUSIONS: The ∼100 known PCa risk variants were shown to effectively stratify PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The 8q24 risk region was also found to be a major contributor to PCa risk in Ugandan men, with the African ancestry-specific risk variant rs72725854 estimated to account for 12% of PCa in this population.
Authors: Nina Mars; Sini Kerminen; Yen-Chen A Feng; Masahiro Kanai; Kristi Läll; Laurent F Thomas; Anne Heidi Skogholt; Pietro Della Briotta Parolo; Benjamin M Neale; Jordan W Smoller; Maiken E Gabrielsen; Kristian Hveem; Reedik Mägi; Koichi Matsuda; Yukinori Okada; Matti Pirinen; Aarno Palotie; Andrea Ganna; Alicia R Martin; Samuli Ripatti Journal: Cell Genom Date: 2022-04-13
Authors: Marco Matejcic; Yesha Patel; Jenna Lilyquist; Chunling Hu; Kun Y Lee; Rohan D Gnanaolivu; Steven N Hart; Eric C Polley; Siddhartha Yadav; Nicholas J Boddicker; Raed Samara; Lucy Xia; Xin Sheng; Alexander Lubmawa; Vicky Kiddu; Benon Masaba; Dan Namuguzi; George Mutema; Kuteesa Job; Dabanja M Henry; Sue A Ingles; Lynne Wilkens; Loic Le Marchand; Stephen Watya; Fergus J Couch; David V Conti; Christopher A Haiman Journal: JCO Precis Oncol Date: 2020-01-31
Authors: Maxine Harlemon; Olabode Ajayi; Paidamoyo Kachambwa; Michelle S Kim; Corinne N Simonti; Melanie H Quiver; Desiree C Petersen; Anuradha Mittal; Pedro W Fernandez; Ann W Hsing; Shakuntala Baichoo; Ilir Agalliu; Mohamed Jalloh; Serigne M Gueye; Nana Yaa F Snyper; Ben Adusei; James E Mensah; Afua O D Abrahams; Akindele O Adebiyi; Akin T Orunmuyi; Oseremen I Aisuodionoe-Shadrach; Maxwell M Nwegbu; Maureen Joffe; Wenlong C Chen; Hayley Irusen; Alfred I Neugut; Yuri Quintana; Moleboheng Seutloali; Mayowa B Fadipe; Christopher Warren; Marcos H Woehrmann; Peng Zhang; Chrissie M Ongaco; Michelle Mawhinney; Jo McBride; Caroline V Andrews; Marcia Adams; Elizabeth Pugh; Timothy R Rebbeck; Lindsay N Petersen; Joseph Lachance Journal: Cancer Res Date: 2020-05-11 Impact factor: 12.701
Authors: Kimberly R Jenkins; Taofik Oyekunle; Lauren E Howard; Emily K Wiggins; Stephen J Freedland; Emma H Allott Journal: Cancer Causes Control Date: 2021-02-02 Impact factor: 2.506