NFκB1 and NFκBIA Polymorphisms Are Associated with Increased Risk for Sporadic Colorectal Cancer in a Southern Chinese Population

• DOI: 10.1371/journal.pone.0021726
• Publication Date: 2011-06-30T16:59:04Z
• Authors: Shunxin Song; Dianke Chen; Jiachun Lu; Jiawei Liao; Yanxin Luo; Zuli Yang; Xinhui Fu; Xinjuan Fan; Yisheng Wei; Lei Yang; Lei Wang; Jianping Wang
• Keywords: Male; Polymorphism, Genetic; Genotype; Science; Q; R; NF-kappa B; Middle Aged; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Asian People; NF-KappaB Inhibitor alpha; Case-Control Studies; Medicine; Humans; Female; Genetic Predisposition to Disease; I-kappa B Proteins; Colorectal Neoplasms; Research Article

Background Nuclear factor κB (NFκB) plays a key role in the regulation of apoptosis. The function NFκB is inhibited by binding to inhibitor (IκB), and disruption balance IκB related development many diseases, including tumors. Therefore, we hypothesized that NFκB1 (-94del/insATTG) NFκBIA (2758 A>G) polymorphisms were associated with colorectal cancer (CRC) susceptibility. Methods In hospital-based case–control study 1001 CRC patients 1005 cancer-free controls frequency matched age sex, genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method performed luciferase assays Western blotting analysis identify whether genetic variants alter its gene expressions functions thus risk. Results We found both NFκB1-94 ins/delATTG 2758 A>G correlated risk (OR = 1.47; 95%CI 1.14–1.86, OR 1.38; 95% CI 1.14–1.66, respectively). Furthermore, when evaluated these two together, combined genotypes 2 variant (risk) alleles (2758GG -94ins/ins+del/ins) an increased 1.71; 1.23–2.38) compared 0 variant, significant trend for more pronounced among subgroups aged <60 years, women, never drinkers, smokers, persons normal BMI those family history cancer(Ptrend<0.01). Moreover, showed G allele 3′UTR significantly decreased mRNA stability A miRNA449a vitro protein expression levels AA+AG carriers higher peritumoral tissues than 2758GG genotype. Conclusion appear jointly contribute CRC. These may be modifier susceptibility this southern Chinese population.