12-lipoxygenase (12-LOX) pathway which produces 12-HETE and hepoxiline HXA3 and HXB3, and induces production of reactive oxygen species and inflammation is increasingly being implicated in variety of cancers, including those of colorectal and thyroid cancers. Hence, we examined whether the functional polymorphism of 12-LOX (mRNA A835G; Protein Gln261Arg) has any association with human colorectal and thyroid cancers. In this communication, we report that the mutation is linked to colorectal cancer and thyroid cancers. Further, we also observed that the heterozygous mutant (AG) is more prevalent in females than in males. Frequencies of AA, AG and GG, respectively were 62.5, 36.2 and 1.3 % in controls, 36.5, 61.5 and 2.0 % in colorectal cancer cases and 35.6, 62.4 and 2.0 % in thyroid cancer cases. The results obtained suggested a significant association of the heterogenous variant (AG) with the cancers. Relative risk of the cancers with the presence of the AG variant was found to be 2.9 and 4.0 for colorectal and thyroid cancers, respectively. However, the association of the variant (AG) was significant only in male colorectal cancer patients but not in female patients. On the other hand, prevalence of the AG variant is significantly higher in control females than in male control subjects. To the best of our knowledge, this is the first study that links the 12-LOX gene polymorphism with thyroid cancer and reveals a gender bias in the prevalence of the polymorphic variants in controls and colorectal cancer patients.