Family history of early onset acute lymphoblastic leukemia is suggesting genetic associations

Childhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0-4, 5-34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5-34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions.The study was supported by the European Union's Horizon 2020 research and innovation program, Grant No 856620, the Swedish Research Council (2016-01176; 2018-02400) and the ALF project grant, Region Skane/ Lund University, Sweden