The combined effects of smoking and the genetic variants on colorectal cancer risk may differ by i) metabolism of PAH, HCA and nitrosamine supported too by cytochrome (CYP1A1, CYP1A2, CYP2E1, and CYP2A6), glutathione-S-transferase (GSTM1, GSTT1, and GSTP1) and N–acetyltransferase, ii) levels of carcinogen intake. Here, CYP2A6 is linked to colorectal cancer.