title: Race-associated biological differences among Luminal A breast tumors.
abstract: African-American (AA) women have higher breast cancer-specific mortality rates. A higher prevalence of the worse outcome Basal-like breast cancer subtype contributes to this, but AA women also have higher mortality even within the more favorable outcome Luminal A breast cancers. These differences may reflect treatment or health care access issues, inherent biological differences, or both. To identify potential biological differences by race among Luminal A breast cancers, gene expression data from 108 CAU and 57 AA breast tumors were analyzed. Race-associated genes were evaluated for associations with survival. Finally, expression of race- and survival-associated genes was evaluated in normal tissue of AA and CAU women. Six genes (ACOX2, MUC1, CRYBB2, PSPH, SQLE, TYMS) were differentially expressed by race among Luminal A breast cancers and were associated with survival (HR <0.8, HR >1.25). For all six genes, tumors in AA had higher expression of poor prognosis genes (CRYBB2, PSPH, SQLE, TYMS) and lower expression of good prognosis genes (ACOX2, MUC1). A score based on all six genes predicted survival in a large independent dataset (HR = 1.9 top vs. bottom quartile, 95% CI: 1.4-2.5). For four genes, normal tissue of AA and CAU women showed similar expression (ACOX2, MUC1, SQLE, TYMS); however, the poor outcome-associated genes CRYBB2 and PSPH were more highly expressed in AA versus CAU women's normal tissue. This analysis identified gene expression differences that may contribute to mortality disparities and suggests that among Luminal A breast tumors there are biological differences between AA and CAU patients. Some of these differences (CRYBB2 and PSPH) may exist from the earliest stages of tumor development, or may even precede malignancy.
authors.affiliation: Department of Epidemiology, CB 7435, North Carolina Central University, 135 Dauer Drive, Durham, NC, USA, mdarcy@email.unc.edu.
authors.forename: Monica
authors.initials: M
authors.lastname: D'Arcy
authors.forename: Jodie
authors.initials: J
authors.lastname: Fleming
authors.forename: Whitney R
authors.initials: WR
authors.lastname: Robinson
authors.forename: Erin L
authors.initials: EL
authors.lastname: Kirk
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D047368:Tumor Burden; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor