Generalizability of Established Prostate Cancer Risk Variants in Men of African Ancestry

Details

• Alternative Title:
  Int J Cancer
• Personal Author:
  Han, Ying ; Signorello, Lisa B. ; Strom, Sara S. ; Kittles, Rick A. ; Rybicki, Benjamin A. ; Stanford, Janet L. ; Goodman, Phyllis J. ; Berndt, Sonja I. ; Carpten, John ; Casey, Graham ; Chu, Lisa ; Conti, David V. ; Rand, Kristin A. ; Diver, W. Ryan ; Hennis, Anselm JM ; John, Esther M. ; Kibel, Adam S. ; Klein, Eric A. ; Kolb, Suzanne ; Le Marchand, Loic ; Leske, M. Cristina ; Murphy, Adam B. ; Neslund-Dudas, Christine ; Park, Jong Y. ; Pettaway, Curtis ; Rebbeck, Timothy R. ; Gapstur, Susan M. ; Zheng, S. Lilly ; Wu, Suh-Yuh ; Witte, John S. ; Xu, Jianfeng ; Isaacs, William ; Ingles, Sue A. ; Hsing, Ann ; Easton, Douglas F. ; Eeles, Rosalind A. ; Schumacher, Fredrick R. ; Chanock, Stephen ; Nemesure, Barbara ; Blot, William J. ; Stram, Daniel O. ; Henderson, Brian E. ; Haiman, Christopher A.
• Corporate Authors:
  The PRACTICAL Consortium ; The ELLIPSE GAME-ON Consortium
• Description:
  Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.
• Subjects:
  Black People Case-Control Studies Cohort Studies Follow-Up Studies Genetic Predisposition To Disease Genome-Wide Association Study Humans Male Polymorphism, Single Nucleotide Prognosis Prostatic Neoplasms Risk Factors

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• Keywords:
  African Ancestry Generalizability Genetic Risk Variant Prostate Cancer
• Source:
  Int J Cancer. 136(5):1210-1217
• Pubmed ID:
  25044450
• Pubmed Central ID:
  PMC4268262
• Document Type:
  Journal Article
• Funding:
  16563/CRUK_/Cancer Research UKUnited Kingdom/ ; C16913/A6135/CRUK_/Cancer Research UKUnited Kingdom/ ; N01-PC-35139/PC/NCI NIH HHSUnited States/ ; R01 CA092447/CA/NCI NIH HHSUnited States/ ; CA056678/CA/NCI NIH HHSUnited States/ ; C5047/A10692/CRUK_/Cancer Research UKUnited Kingdom/ ; CA082664/CA/NCI NIH HHSUnited States/ ; CA148085/CA/NCI NIH HHSUnited States/ ; R01 CA063464/CA/NCI NIH HHSUnited States/ ; R01 CA082664/CA/NCI NIH HHSUnited States/ ; CA092447/CA/NCI NIH HHSUnited States/ ; U01 HG004726/HG/NHGRI NIH HHSUnited States/ ; ES011126/ES/NIEHS NIH HHSUnited States/ ; CA54281/CA/NCI NIH HHSUnited States/ ; RC2 CA148085/CA/NCI NIH HHSUnited States/ ; ES007784/ES/NIEHS NIH HHSUnited States/ ; CA127298/CA/NCI NIH HHSUnited States/ ; CA092579/CA/NCI NIH HHSUnited States/ ; U10 CA037429/CA/NCI NIH HHSUnited States/ ; 1 U19 CA148537-01/CA/NCI NIH HHSUnited States/ ; C5047/A7357/CRUK_/Cancer Research UKUnited Kingdom/ ; CA1326792/CA/NCI NIH HHSUnited States/ ; P50 CA140388/CA/NCI NIH HHSUnited States/ ; 1U58DP000807-3/DP/NCCDPHP CDC HHSUnited States/ ; U01 CA127298/CA/NCI NIH HHSUnited States/ ; UG1 CA189974/CA/NCI NIH HHSUnited States/ ; C5047/A3354/CRUK_/Cancer Research UKUnited Kingdom/ ; R01 CA068578/CA/NCI NIH HHSUnited States/ ; HG004726/HG/NHGRI NIH HHSUnited States/ ; R01 CA056678/CA/NCI NIH HHSUnited States/ ; 17528/CRUK_/Cancer Research UKUnited Kingdom/ ; R25 CA174664/CA/NCI NIH HHSUnited States/ ; CA63464/CA/NCI NIH HHSUnited States/ ; U58 DP000807/DP/NCCDPHP CDC HHSUnited States/ ; P30 CA076292/CA/NCI NIH HHSUnited States/ ; R01 DK101855/DK/NIDDK NIH HHSUnited States/ ; U19 CA148537/CA/NCI NIH HHSUnited States/ ; P30 ES007784/ES/NIEHS NIH HHSUnited States/ ; R01 CA054281/CA/NCI NIH HHSUnited States/ ; U01 CA063464/CA/NCI NIH HHSUnited States/ ; P30 CA068485/CA/NCI NIH HHSUnited States/ ; R01 CA088164/CA/NCI NIH HHSUnited States/ ; CA140388/CA/NCI NIH HHSUnited States/ ; 10118/CRUK_/Cancer Research UKUnited Kingdom/ ; CA68485/CA/NCI NIH HHSUnited States/ ; S06 GM008016/GM/NIGMS NIH HHSUnited States/ ; R01 ES011126/ES/NIEHS NIH HHSUnited States/ ; 11022/CRUK_/Cancer Research UKUnited Kingdom/ ; R01 CA092579/CA/NCI NIH HHSUnited States/ ; U01 CA136792/CA/NCI NIH HHSUnited States/ ; 15007/CRUK_/Cancer Research UKUnited Kingdom/ ; N01PC35139/CA/NCI NIH HHSUnited States/ ; R37 CA054281/CA/NCI NIH HHSUnited States/ ; S06GM08016/GM/NIGMS NIH HHSUnited States/ ; C1287/A10118/CRUK_/Cancer Research UKUnited Kingdom/ ; UM1 CA182883/CA/NCI NIH HHSUnited States/
• Volume:
  136
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:6a8a94754a6b99ce8f305dae89ff9c8e8b504837c20497d2a51c7ff390390d17
• Download URL:
  https://stacks.cdc.gov/view/cdc/30204/cdc_30204_DS1.pdf
• File Type:
  [PDF - 482.47 KB ]