(a) The Leu-432 allele of CYP1B1 has been associated with a greater frequency [odds-ratio (O.R.)>4] of TP53 gene mutations and HNSCC in cigarette smokers [16]; however, this “greater risk” is difficult to reconcile experimentally—given the fact that the Leu-432 mutant was shown in an E. coli expression assay in vitro to metabolize PAHs only 1.2- to 1.5-fold better than the Val-432 variant [42]. Here, CYP1B1 is linked to head and neck squamous cell carcinoma.