The inhibitory protein IjBa, encoded by the NFKBIA gene, plays an important role in regulating the activity of nuclear factor-kappa B, a transcription factor which has been implicated in the initiation and progression of cancers. This study aimed to evaluate the association of NFKBIA -826C[T (rs2233406) and -881A[G (rs3138053) polymorphisms with the risk of sporadic colorectal cancer (CRC) in Malaysian population. A case-control study comprising 474 subjects (237 CRC patients and 237 cancer-free controls) was carried out. The polymorphisms were genotyped from the genomic DNA of the study subjects employing PCR-RFLP, followed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95 % confidence intervals (CIs) using unconditional logistic regression analysis. The two polymorphisms were in complete and perfect linkage disequilibrium (D 0 = 1.0, r 2 = 1.0). Overall, no statistically significant CRC risk association was found for the polymorphisms (P [ 0.05). A similar lack of association was observed when the data were stratified according to ethnicity (P [ 0.05). However, stratification by gender revealed a significant inverse association between the heterozygous genotype of the polymorphisms and the risk of CRC among females (OR 0.53, 95 % CI 0.29-0.97, P = 0.04), but not among males (P [ 0.05). In conclusion, the heterozygous genotype of the polymorphisms could contribute to a significantly decreased CRC risk among females, but not males, in the Malaysian population.
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