The APCDD1 variant was identified in 8 additional familial CRC cases, 1 CRC case without family history and in 2 healthy elderly individuals without cancer family history, leading to a 4.9-fold increased CRC risk for the variant carriers (p = 0.04), while no other HDAC5 variants were identified among the 1705 familial CRC cases. The gene discussed is HDAC5; the disease is cancer.