The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer

• Published in: Cancer epidemiology Vol. 37; no. 5; pp. 634 - 638
• Main Authors: Mohd Suzairi, Mohd Shafi’i, Tan, Shing Cheng, Ahmad Aizat, Abdul Aziz, Mohd Aminudin, Mustapha, Siti Nurfatimah, Mohd Shahpudin, Andee, Zakaria Dzulkarnaen, Ankathil, Ravindran
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.10.2013; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Analysis. Health state; Base Sequence; Biological and medical sciences; Cancer; Case-Control Studies; Colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Enzymes; Epidemiology; Female; Gene Frequency; General aspects; Genes; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Hematology, Oncology and Palliative Medicine; Hospitals; Humans; INDEL Mutation; Internal Medicine; Malaysia - epidemiology; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Mortality; NF-kappa B p50 Subunit - genetics; NFKB1; Pathogenesis; Polymerase Chain Reaction; Polymorphism; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Population; Predisposition; Promoter Regions, Genetic; Proteins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk; rs28362491; Smoking; Statistical analysis; Studies; Susceptibility; Tumors; Young Adult; Malaysia; rs28362491; Susceptibility; Colorectal cancer; Predisposition; Risk; NFKB1; Polymorphism; Rectal disease; Genetic variability; Sporadic; Insertion; Genotype; Increase; Malignant tumor; Colonic disease; Promoter; Sensitivity; Gene; Risk factor; Deletion; Digestive diseases; Intestinal disease; Genetics; Cancer
• ISSN: 1877-7821; 1877-783X
• DOI: 10.1016/j.canep.2013.05.007

Abstract Objective : To investigate the allele and genotype frequencies of NFKB1 −94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population. Methods : Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 −94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed 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. Results : The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls ( P < 0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR = 2.42, 95% CI = 1.24–4.73, P < 0.01). Conclusions : The variant allele of NFKB1 −94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population.