Genetic Insights into Interleukin-13 Polymorphisms in Colorectal Cancer Risk and Progression

<h3>Abstract</h3> <h3>Background/Aim:</h3> Colorectal cancer (CRC) is a major global health burden with increasing incidence and significant mortality, particularly in advanced stages. Genetic susceptibility and inflammation-related pathways, including cytokine signaling, are increasingly recognized as key contributors to CRC pathogenesis. Interleukin-13 (IL-13) polymorphisms, particularly rs1800925 and rs20541, have been implicated in cancer biology; however, their roles in CRC remain inconclusive. <h3>Materials and Methods:</h3> A hospital-based case-control study was conducted in Taiwan, including 362 CRC patients and 362 age- and sex-matched controls. Genomic DNA was extracted from peripheral blood, and <i>IL-13</i> rs1800925 and rs20541 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. Associations between genotypes and CRC risk and clinicopathological features were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). <h3>Results:</h3> The genotype distributions of rs1800925 and rs20541 in controls conformed to the Hardy-Weinberg equilibrium (<i>p</i>=0.2098 and 0.7888, respectively). No overall significant associations were observed between <i>IL-13</i> polymorphisms and CRC susceptibility. For rs1800925, the CT and TT genotypes showed ORs of 1.20 (95%CI=0.88-1.65, <i>p</i>=0.2772) and 1.42 (95%CI=0.80-2.54, <i>p</i>=0.2844), respectively. For rs20541, the AG and AA genotypes exhibited ORs of 1.11 (95%CI=0.82-1.51, <i>p</i>=0.5581) and 1.21 (95%CI=0.74-1.98, <i>p</i>=0.5185). However, rs1800925 CT+TT genotypes were associated with significantly increased risk of distant metastasis at diagnosis (OR=2.12, 95%CI=1.40-3.20, <i>p</i>=0.0005), while rs20541 AG+AA genotypes were associated with advanced stage (OR=1.50, 95%CI=1.03-2.19, <i>p</i>=0.0423) and metastatic disease at diagnosis (OR=2.16, 95%CI=1.39-3.36, <i>p</i>=0.0007). <h3>Conclusion:</h3> Although <i>IL-13</i> rs1800925 and rs20541 polymorphisms are not associated with CRC susceptibility, they may be associated with clinicopathological aggressiveness at diagnosis, highlighting their potential utility in stratifying CRC severity, particularly in the Taiwanese population.