Ferroptosis-Related APOE, BCL3 and ALOX5AP Gene Polymorphisms are Associated with the Risk of Thyroid Cancer

Abstract

Purpose: This study aimed to evaluate the association between polymorphisms in the ferroptosis-related genes apolipoprotein E (APOE), BCL3 transcription coactivator (BCL3) and arachidonate 5-lipoxygenase activating protein (ALOX5AP) and the risk of thyroid cancer. Methods: Six single nucleotide polymorphisms (SNPs) of APOE (rs429358 and rs7412), BCL3 (rs34698726 and rs8100239) and ALOX5AP (rs4076128 and rs4073259) were genotyped in 520 papillary thyroid carcinoma cases and 520 healthy controls using the MassARRAY platform. Results: The rs429358-TC, rs34698726-TA/TT, and rs8100239-AT/AA genotypes exhibited an elevated risk of thyroid cancer (prs429358 = 0.002, prs34698726 = 0.007, prs8100239 = 0.002), while rs7412-CT/TT and rs4076128-GA/GG were found to be protective genotypes against the risk of disease (prs7412 = 0.0003, prs4076128 = 0.0001). Genetic model analysis showed that APOE-rs429358 was correlated with an increased risk of disease under dominant and log-additive models (pdominant = 0.0004, plog-additive = 0.0006). BCL3-s34698726 and rs8100239 were associated with an elevated risk of disease under all three genetic models (p < 0.05). In contrast, APOE-rs7412 was related to a decreased risk of thyroid cancer under dominant and log-additive models (pdominant = 0.0001, plog-additive = 0.0001). Moreover, ALOX5AP-rs4076128 was also correlated with a reduced risk of disease under all three genetic models (p < 0.05). Conclusion: The results help us better understand how genetic polymorphisms in ferroptosis-related genes are relevant to thyroid cancer susceptibility.