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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
CYP3A4-V and prostate cancer in African Americans: Causal or confounding association because of population stratification?
Human Genetics, Volume 110, No. 6, Year 2002
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Description
CYP3A4-V, an A to G promoter variant associated with prostate cancer in African Americans, exhibits large differences in allele frequency between populations. Given that the African American population is genetically heterogeneous because of its African ancestry and subsequent admixture with European Americans, case-control studies with African Americans are highly susceptible to spurious associations. To test for association with prostate cancer, we genotyped CYP3A4-V in 1376 (2 N) chromosomes from prostate cancer patients and age- and ethnicity-matched controls representing African Americans, Nigerians, and European Americans. To detect population stratification among the African American samples, 10 unlinked genetic markers were genotyped. To correct for the stratification, the uncorrected association statistic was divided by the average of association statistics across the 10 unlinked markers. Sharp differences in CYP3A4-V frequencies were observed between Nigerian and European American controls (0.87 and 0.10, respectively; P<0.0001). African Americans were intermediate (0.66). An association uncorrected for stratification was observed between CYP3A4-V and prostate cancer in African Americans (P=0.007). A nominal association was also observed among European Americans (P=0.02) but not Nigerians. In addition, the unlinked genetic marker test provided strong evidence of population stratification among African Americans. Because of the high level of stratification, the corrected P-value was not significant (P=0.25). Follow-up studies on a larger dataset will be needed to confirm whether the association is indeed spurious; however, these results reveal the potential for confounding of association studies by using African Americans and the need for study designs that take into account substructure caused by differences in ancestral proportions between cases and controls. © Springer-Verlag 2002.
Authors & Co-Authors
Kittles, Rick A.
United States, Washington, D.c.
Howard University College of Medicine
United States, Washington, D.c.
Howard University Hospital
United States, Washington, D.c.
Howard University
Chen, Weidong
United States, Washington, D.c.
Howard University College of Medicine
Panguluri, Ramesh C.K.
United States, Washington, D.c.
Howard University College of Medicine
Ahaghotu, Chiledum A.
United States, Washington, D.c.
Howard University Hospital
United States, Washington, D.c.
Howard University
Jackson, Aaron G.
United States, Washington, D.c.
Howard University Hospital
Adebamowo, Clement
Nigeria, Ibadan
University College Hospital, Ibadan
Griffin, Robin
United States, Washington, D.c.
Howard University College of Medicine
Williams, Tyisha
United States, Washington, D.c.
Howard University College of Medicine
Ukoli, Flora Aroma Mene
United States, Washington, D.c.
Howard University
Adams-Campbell, Lucile Lauren
United States, Washington, D.c.
Howard University
Kwagyan, John
United States, Washington, D.c.
Howard University College of Medicine
Isaacs, William B.
United States, Baltimore
The Sidney Kimmel Comprehensive Cancer Center
Freeman, Vincent L.
United States, Chicago
Loyola University Chicago
Dunston, Georgia M.
United States, Washington, D.c.
Howard University College of Medicine
United States, Washington, D.c.
Howard University
Statistics
Citations: 158
Authors: 14
Affiliations: 6
Identifiers
Doi:
10.1007/s00439-002-0731-5
ISSN:
03406717
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study