Abstract
Background: Chronic inflammation is an important pathological factor in colorectal tumorigenesis. Lymphotoxin-alpha (LT-alpha), a pleiotropic pro-inflammatory cytokine has been shown to possess both cancer promoting and cancer inhibiting activities. Several studies have analyzed the association of intronic LT-alpha+252A/G single-nucleotide polymorphism (SNP) in human LT-alpha gene with various cancers including colorectal cancer (CRC), but the outcome have been mixed and inconclusive. Materials and Methods: The present case-control study analyzed the association of LT-alpha+252A/G SNP with CRC risk in the ethnic Kashmiri population. The genotype frequencies of LT-alpha+252A/G intronic SNP were compared between 142 CRC patients and 184 individually matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism method. The association between the LT-alpha+252A/G SNP and CRC risk was investigated through conditional logistic regression models adjusted for multiple possible confounding (third) variables. Further, the association between CRC risk and various clinico-pathological parameters, demographic variables, and environmental factors within the case group subjects and the SNP under study was also analyzed. Results: The overall association between the LT-alpha+252A/G SNP and the modulation of CRC risk was found to be significant (P = 0.013). Further, we found a significant effect modification of the association between the LT-alpha+252A/G SNP genotypes and CRC risk by gender (P = 0.046). We also found that the LT-alpha+252A/G SNP within the case group was significantly associated with gender (P = 0.0014) and lymph node status (P < 0.0001). Conclusion: This study has demonstrated that LT-alpha+252A/G SNP is significantly associated with risk of CRC in the ethnic Kashmiri population although the nature of this association could not be deciphered further in a statistically significant manner. However, this study needs to be replicated with larger sample size and if possible in other ethnically defined populations that exhibit comparable incidence of CRC to substantiate and elaborate our findings in a more comprehensive manner.