H2AFX variants are associated with an increased risk of breast cancer (BC). H2AFX gene encodes a member of the H2A histone family which is central in the detection of and response to DNA double-strand breaks. In somatic cells, H2afx and Mdc1 are close functional partners in DNA repair and damage response. Due to the critical role of the H2AX histone variant in double-strand break repair, genetic variants in the H2AX gene, H2AFX, may influence cancer susceptibility. H2AFX encodes a histone variant involved in signaling sites of DNA damage and recruiting repair factors. Genetic variants in H2AFX may influence risk of non-Hodgkin lymphoma (NHL), a heterogeneous group of lymphoid tumors that are characterized by chromosomal translocations.