Our in vitro and in vivo data provided evidence that three inherited causal variations rs17336602 (G>C), rs4770489 (A>G), and rs34354770 (A>C) in 13q12.12 contributed to the lung cancer risk by attenuating the p53-responsive enhancer-mediated TNFRSF19 activation. The gene discussed is TNFRSF19; the disease is lung cancer.