Abstract. the overexpression of arachidonyl lipoxygenase-12 (alOx12) in breast cancer has been reported. hence, we examined whether a non-synonymous polymorphism of alOx12 (mrna, a835G; Gln261arg) is associated with breast cancer in females. the polymorphism was detected in genomic dna by pcr-rFlp. the association between the a835G polymorphism and breast cancer risk was measured by odds ratio (OR) with 95% confidence intervals (CIs) using Fisher's exact test, and differences were considered significant at p<0.05. the frequencies of aa (wild-type), GG (homozygous variant) and aG (heterozygous variant) were 59.5, 0.9 and 39.6% in the controls, and 39.3, 2.5 and 58.2% in the breast cancer cases, respectively. the frequency of the aG genotype was higher in the patients compared to the controls (p<0.0014). the frequency of the GG variant was 2.5 and 0.9% in the cancer subjects and controls, respectively. the relative risk of breast cancer was 2 times greater (Or=2.227) at 95% ci when compared to the relative risk of the heterozygous variant. For the GG genotype, the risk was 4 times greater (Or=4.125) at 95% ci than that of the controls, suggesting a positive association of the aG genotype with the occurrence of breast cancer. the frequencies of the polymorphism were different in different populations. the arg/Gln and arg/arg variants were associated with an increased risk of breast cancer, and the frequencies of the variants differed considerably among various populations. The identification of a gene with links to breast cancer may impact screening, diagnosis and drug development.
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.
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