Given that chemotherapy-mediated intracellular upregulation of ROS activates hypoxia signaling and then confers cancer cells to chemotherapy resistance [37, 38], we speculated that hypercholesterolemia may also upregulate intracellular ROS levels to activate the hypoxia signaling and subsequent NO/NOS expression in CRC. The gene discussed is NOS2; the disease is familial hypercholesterolemia.