4. 12-Lipoxygenase (12-LOX)
An earlier study suggested that the 12-LOX-mediated pathway is associated with the risk of colorectal cancer . The best-studied example includes mutation of E261R (835A>G), which causes an increase in 12-LOX activity, with a potential link to esophageal squamous cell carcinoma . This mutation has also been associated with colorectal cancer  and  and breast cancer . An in vitro and in vivo study has shown that 12-LOX plays a role in the proliferation and antiapoptosis of hepatocellular cells, suggesting that this carcinogenic function of ALOX12 requires endogenously generated lipid mediators .
Consistent with the FG2216 of ALOX12 in the platelets of humans, mice lacking Alox12 have shown increased platelet sensitivity and mortality due to thrombosis in response to the administration of adenosine diphosphate, whereas aggregation and secretion in response to most agonizts seemed normal . Alox12 deficiency has led to a reduced incidence of carcinoma in a C57BL6/129 genetic background and of papilloma in a tumor-sensitive SENCAR genetic background, showing that Alox12 is involved in tumorigenesis in the skin in a context-dependent manner . Most notably, Alox12 deficiency has caused basal transepidermal water loss in the skin with unaltered inflammatory responses in Alox12b- and Aloxe3-deficient mice . This finding suggests that Alox12 has a critical role in the maintenance of the skin barrier in association with other isoforms, as explained in detail later.