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FOXP3 (forkhead box P3: also known as IPEX, XPID) is not only a hallmark of immunosuppressive regulatory T cells (Tregs), but also an X‐linked breast cancer suppressor gene expressed in tumor cells. A two‐stage investigation was conducted in individuals from northern, southern and eastern China. Individuals carrying a FOXP3 rs2294021CT genotype showed about 1.5‐fold increased risk of breast cancer compared with TT carriers. In a related biochemical assay, the rs2294021C allele was found to significantly enhance transcription activity, leading to higher mRNA levels of FOXP3 compared with T allele. Moreover, the number of Tregs and its corresponding interleukin‐10 (IL‐10) secretion were elevated whereas the proliferation of antitumor T cells was decreased in the C‐allele carriers. The breast cancer oncogenes Her‐2/ErbB2 and Skp2 were also found to be significantly inhibited in C‐allele carriers …