Chronic inflammation is a key factor in the development of colorectal cancer (CRC). Lymphotoxin-alpha (LT-α), a multifunctional pro-inflammatory cytokine, has shown both tumor-promoting and tumor-suppressing properties. The relationship between the intronic LT-α +252A/G single-nucleotide polymorphism (SNP) and various cancers, including CRC, has been widely studied with inconsistent findings. This study investigated the association between the LT-α +252A/G SNP and CRC susceptibility in the Kashmiri population. The frequencies of LT-α +252A/G SNP genotypes were compared between 142 CRC patients and 184 healthy controls using PCR-RFLP. Logistic regression models, adjusted for potential confounders, were used to assess the association between the SNP and CRC risk. The study also evaluated the relationship between clinicopathological characteristics, environmental factors, and the SNP in the case group. A significant association was found between the LT-α +252A/G SNP and CRC risk (P = 0.013). The effect of this association was influenced by gender (P = 0.046). In addition, significant correlations were observed between the SNP and gender (P = 0.0014) and lymph node status (P < 0.0001) in the case group. Our findings suggest that the LT-α +252A/G SNP is associated with CRC risk in the Kashmiri population, although further research is needed to clarify the specifics of this association. Replication of the study with larger sample sizes and among different populations is necessary to confirm and enhance the results.
