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Introduction: The Black population in the US is heterogeneous but is often treated as monolithic in research, with skin pigmentation being the primary indicator of racial classification. Objective: This paper examines the differences among Blacks by comparing genetic ancestry, skin color and social attainment of 259 residents across four US cities-Norman, Oklahoma; Cincinnati, Ohio; Harlem, New York; and Washington, District of Columbia., Methods: Participants were recruited between 2004 and 2006 at community-based forums. Cross-sectional data were analyzed using chi-square tests, correlation analyses and logistic regression., Results: There were variations in ancestry, melanin index and social attainment across some cities. Overall, men with darker skin color, and women with lighter skin color were significantly more likely to be married. Darker skin individuals with significantly more West African ancestry reported attainment of graduate degrees, and professional occupations than lighter skin individuals., Conclusions: Our findings suggest differences in skin pigmentation by geography and support regional variations in ancestry of US Blacks. Biomedical research should consider genetic ancestry and local historical/social context rather than relying solely on skin pigmentation as a proxy for race., Competing Interests: Dr. Rick Kittles has financial interests in an ancestry DNA testing company and/or products. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have no competing interests.

Insulin-like growth factor (IGF)-1 and Insulin-like growth factor binding protein-3 (IGFBP-3) are strong inhibitors of apoptosis and play a role in mediating the effects of growth hormone. Both IGF-1 and IGFBP-3 serum levels have been linked to cancer risk. Here, we explore the relationship between three common IGF polymorphisms [C/T single-nucleotide polymorphism (SNP) (rs7965399) and a dinucleotide repeat (CA)n within the 5' regulatory region of the IGF-1 gene and the -202 A/C SNP in the IGFBP-3 gene], serum levels and prostate cancer (Pca) risk in 767 African-Americans enrolled in a clinic-based case-control study. IGF-1 and IGFBP-3 levels were measured using immunochemiluminometric assay and the three polymorphisms were typed for 401 Pca cases and 366 age- and ethnicity-matched controls. Multiple linear regression and multivariable unconditional logistic regression were used to test for associations between genotypes and circulating IGF levels and Pca risk, respectively. The presence of at least one copy of the IGFBP-3 -202 C allele was strongly associated with lower IGFBP-3 serum levels (3532 versus 3106 ng/ml; P = 0.008). We also observed a 2-fold increase in Pca risk for individuals homozygous for the IGFBP-3 -202 C allele [odds ratio = 2.4; 95% confidence interval = 1.2-4.8). Furthermore, IGF-1 (CA)19 genotypes were significantly associated with lower IGFBP-3 serum levels (P = 0.003). Our results reveal that variation in the 5'-untranslated region of the IGF-1 and IGFBP-3 genes may be influencing IGF serum levels and Pca risk in African-Americans and suggest a need to explore this variation across diverse populations. Our study adds clarity and further support to the previous findings, implicating serum IGFBP-3 levels and the IGFBP-3 -202 A/C SNP in prostate carcinogenesis.