Molecular subtypes including the normal-like subtype drive patient outcomes in human breast cancer but the biological basis underlying subtype-specific disease is not completely understood (1-4). We mined published microarray data (5, 6) to discover in an unbiased fashion the most distinguishing genetic and transcriptional features of tumors of each breast cancer molecular subtype. We previously described clusters of SNPs associated with the basal subtype at 5q14 (7-15), the luminal A subtype

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... 16p12 (16, 17) and 16q21-24 (18-25), the luminal B subtype at 12q14.3 - 12q15 (26-33), and the HER2+ subtype at 17q12 (34-38) and 17q21.1 - 17q.23.1 (39-42). Here we identified a single nucleotide polymorphism, rs617283, residing within C8B, as among the most significant genetic differences in the tumors of patients with normal-like breast cancer. In a separate cohort of patients with normal-like subtype breast cancer, differentially expressed C8B transcripts could not be identified. Analysis of patient survival data revealed that C8B primary tumor expression was correlated with distant metastasis-free survival in patients with basal-like breast cancer. Sequence variation in the C8B gene may be important in understanding differences in genetic background that favor development of normal-like subtype human breast cancer.