title: Gender-specific association of NFKBIA promoter polymorphisms with the risk of sporadic colorectal cancer.
abstract: The inhibitory protein IκBα, 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' = 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.
authors.affiliation: Human Genome Centre, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia, shingchengtan@gmail.com.
authors.forename: Shing Cheng
authors.initials: SC
authors.lastname: Tan
authors.forename: Mohd Shafi'i Mohd
authors.initials: MS
authors.lastname: Suzairi
authors.forename: Abdul Aziz Ahmad
authors.initials: AA
authors.lastname: Aizat
authors.forename: Mustapha Mohd
authors.initials: MM
authors.lastname: Aminudin
authors.forename: Mohd Shahpudin Siti
authors.initials: MS
authors.lastname: Nurfatimah
authors.forename: Venkata Murali Krishna
authors.initials: VM
authors.lastname: Bhavaraju
authors.forename: Biswa Mohan
authors.initials: BM
authors.lastname: Biswal
authors.forename: Ravindran
authors.initials: R
authors.lastname: Ankathil
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha