Though a number of early studies showed the two polymorphisms functionally affect the EPHX1 enzymatic activity [7], [8] and are associated with certain cancers [9]–[18], our systematic analyses revealed that both Y113H low enzymatic activity allele (H) and putative low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R, were significantly associated with decreased risk of lung and UADT cancers, while the putative high EPHX1 enzyme activity was associated with increased risk of these cancers. Here, EPHX1 is linked to cancer.