NF[kappa]B1 and NF[kappa]BIA Polymorphisms Are Associated with Increased Risk for Sporadic Colorectal Cancer in a Southern Chinese Population

Nuclear factor [kappa]B (NF[kappa]B) plays a key role in the regulation of apoptosis. The function of NF[kappa]B is inhibited by binding to NF[kappa]B inhibitor (I[kappa]B), and disruption of the balance of NF[kappa]B and I[kappa]B is related to the development of many diseases, including tumors. Therefore, we hypothesized that the NF[kappa]B1 (-94del/insATTG) and NF[kappa]BIA (2758 A>G) polymorphisms were associated with colorectal cancer (CRC) susceptibility. In a hospital-based case-control study of 1001 CRC patients and 1005 cancer-free controls frequency matched by age and sex, we genotyped polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and performed luciferase assays and Western blotting analysis to identify whether genetic variants in NF[kappa]BIA alter its gene expressions and functions and thus cancer risk. We found that both NF[kappa]B1-94 ins/delATTG and NF[kappa]BIA 2758 A>G polymorphisms were correlated with CRC risk (OR = 1.47; 95%CI = 1.14-1.86, and OR = 1.38; 95% CI = 1.14-1.66, respectively). Furthermore, when evaluated these two polymorphisms together, the combined genotypes with 2 variant (risk) alleles (2758GG and -94ins/ins+del/ins) were associated with an increased risk of CRC (OR = 1.71; 95% CI = 1.23-2.38) compared to 0 variant, and the significant trend for 2 variant (risk) alleles were more pronounced among subgroups of aged