Comparing genetic ancestry and self-described race in african americans born in the United States and in Africa.

Genetic association studies can be used to identify factors that may contribute to disparities in disease evident across different racial and ethnic populations. However, such studies may not account for potential confounding if study populations are genetically heterogeneous. Racial and ethnic classifications have been used as proxies for genetic relatedness. We investigated genetic admixture and developed a questionnaire to explore variables used in constructing racial identity in two cohorts: 50 African Americans and 40 Nigerians. Genetic ancestry was determined by genotyping 107 ancestry informative markers. Ancestry estimates calculated with maximum likelihood estimation were compared with population stratification detected with principal components analysis. Ancestry was approximately 95% west African, 4% European, and 1% Native American in the Nigerian cohort and 83% west African, 15% European, and 2% Native American in the African American cohort. Therefore, self-identification as African American agreed well with inferred west African ancestry. However, the cohorts differed significantly in mean percentage west African and European ancestries (P < 0.0001) and in the variance for individual ancestry (P < or = 0.01). Among African Americans, no set of questionnaire items effectively estimated degree of west African ancestry, and self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry. Our findings suggest that self-reported race and ancestry can predict ancestral clusters but do not reveal the extent of admixture. Genetic classifications of ancestry may provide a more objective and accurate method of defining homogenous populations for the investigation of specific population-disease associations.

17HSD 2 may be higher in African-American breast cancer and is associated with estrogen receptor-negative tumors.

BACKGROUND: African-American women develop more aggressive breast cancers and at an earlier age compared with Caucasian women. MATERIALS AND METHODS: We compared gene expression profiles of breast cancer cell lines that were developed from African-American and Caucasian patients to identify biological differences in breast cancers that develop in these groups. Real-time PCR was used to evaluate mRNA expression in cell lines and in a series of breast cancer cases. Gene microarray signal intensities were also analyzed in the International Genomics Consortium Expression Project for Oncology (expO) dataset. RESULTS: 17,-Hydroxysteroid dehydrogenase type 2 (17HSD 2) gene and mRNA expression were significantly higher in the African-American cell lines (p<0.05). However, 17HSD 2 expression did not differ significantly between the two cohorts in either our clinical series or the expO dataset. 17HSD 2 expression was found to be predictive of younger age at diagnosis and estrogen receptor status. CONCLUSION: Overexpression of 17HSD 2 in African-American breast cancer may contribute to the increased proportion of estrogen receptor-negative breast cancers and worse clinical outcome among African-American patients.

Cyclin D1 overexpression is associated with estrogen receptor expression in Caucasian but not African-American breast cancer.

BACKGROUND: African-American (AA) breast cancer patients consistently show a shortened survival when compared with Caucasian patients. This worse prognosis is most likely due to a combination of socioeconomic factors and differences in tumor biology. Previous studies have demonstrated that cyclin D1 overexpression is strongly associated with estrogen receptor (ER) expression in breast cancer, but these series either included primarily Caucasian patients or did not specify race. MATERIALS AND METHODS. We analyzed 200 breast cancer cases obtained from AA and Caucasian patients who were matched on age, stage, ER status, and year of diagnosis. We examined expression levels of cyclin D1, p53, p27Kip1 (p27), and p21Cip1 (p21), and correlated their expression with ER status. RESULTS: Cyclin D1, p53, p27, and p21 expression rates were similar in matched cases of AA and Caucasian breast cancer (p values>0.05). However, cyclin D1 overexpression was significantly associated with ER status in only the Caucasian (p=0.0005), and not the AA cases (p=0.07). CONCLUSION: This finding suggests a novel biological difference, which may contribute to the more aggressive phenotype of AA breast cancer.