induce mesenchymal-epithelial transition44. Dysfunctional ARHGEF5 acts as an oncogene specific for human breast tissue, with a crucial role in tumorigenesis and metastasis in breast cancer45. MKL1 is also involved in tumor cell invasion and metastasis, particularly in human breast carcinoma46. Two of the newly associated SNPs lie within the TCF7L2 and FTO genes, previously associated with type 2 diabetes and/or obesity through GWAS47–49. TCF7L2 acts as a proto-oncogene and is involved in the Wnt pathway and in tumor formation50. PAX9 at 14q13.3 encodes a transcription factor that regulates cell proliferation, migration and resistance to apoptosis51,52. SSBP4 is involved in DNA recombination and repair and has been suggested to have tumor suppressor activity53,54. The expression of KREMEN1 at 22q12.1 is lower or absent in human tumors compared to normal tissue55,56. This gene encodes a negative regulator of the Wnt/β-catenin pathway, which has a key role in cell fate determination, stem cell regulation and cell differentiation and proliferation. It has been suggested that lack of KREMEN1 would activate the Wnt/β-catenin pathway, thereby enhancing susceptibility to tumorigenesis55,56. Finally, NTN4 at 12q22 encodes a secreted growth factor that regulates tumor growth. High levels of NTN4 have been found in ER-positive but not ER-negative breast
