FOXP3 germline polymorphisms are not associated with risk of breast cancer.

Recent studies have characterized X-linked transcriptional regulator FOXP3 as a tumor suppressor gene involved in the pathogenesis of breast cancer. A high rate of somatic FOXP3 mutations in breast tumors and the consequent upregulation of ERBB2 (alias HER-2) make FOXP3 a good candidate gene for breast cancer susceptibility. By taking advantage of a highly conserved FOXP3 sequence, we genotyped three haplotype-tagging single-nucleotide polymorphisms (htSNPs) that cover 40kb around the FOXP3 gene region in 1,529 cases and 1,528 controls from the large population-based Genetic Epidemiology Breast Cancer (GEBC) study in northern Israel. None of the FOXP3 htSNPs showed strong association with breast cancer risk. There was no evidence for significant heterogeneity by ethnicity (Ashkenazi Jews, Sephardic Jews, Arabs), first-degree family history of breast cancer, or age at diagnosis in stratified analysis. The analysis of reconstructed haplotypes based on the three FOXP3 htSNPs did not identify any haplotypes associated with breast cancer. Although FOXP3 is a biologically relevant gene in the pathogenesis of breast cancer, germline variation was not meaningfully associated with risk of the disease.