Abstract
BackgroundFamily history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.MethodsIndividual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.ResultsMean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered “no” to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.ConclusionsMean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
Highlights
Prostate cancer (CaP) is the most common cancer diagnosed in men and the second leading cause of cancer death among men in the US, with African American (AA) men having substantially higher CaP incidence and mortality rates than men self-reporting as European American (EA)
The population-based sample of incident CaP cases is composed of 2106 men (1043 AA and 1063 EA) with genetic data, with 1176 research subjects from 42 counties in central and eastern North Carolina and 930 research subjects from 21 parishes in Louisiana (13 parishes surrounding New Orleans and 8 parishes in southern Louisiana, which were added as a result of population displacement due Hurricane Katrina which occurred on August 29, 2005)
Mean Centre d’Etude du Polymorphisme Humain (CEU) and YRI (YRI only) ancestry in participants self-reporting as Black/ African American did vary significantly between North Carolina and Louisiana, p,0.03 (p,0.007)
Summary
Prostate cancer (CaP) is the most common cancer diagnosed in men and the second leading cause of cancer death among men in the US, with African American (AA) men having substantially higher CaP incidence and mortality rates than men self-reporting as European American (EA). A positive family history is one of the strongest known risk factors for CaP and quantitative estimates from twin studies indicate that 42% of CaP cases may have a heritable component [3], which is stronger than any other common cancer [4,5,6,7]. Failure to adjust for genetic race and ethnicity in analyses of genetic susceptibility to disease incidence and aggressiveness has been shown to reduce power and increase false positive findings [13,14,15]. History and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP
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