Effects of NFKB1 and NFKBIA gene polymorphisms on susceptibility to environmental factors and the clinicopathologic development of oral cancer
Journal
PLoS ONE
Journal Volume
7
Journal Issue
4
Pages
e35078
Date Issued
2012
Author(s)
Abstract
Background: Oral cancer, which is the fourth most common cancer in Taiwanese men, is associated with environmental carcinogens. The possibility that genetic predisposition in nuclear factor-kappa B (NF-κB)-signaling pathways activation is linked to the development of oral squamous cell carcinoma (OSCC) requires investigation. The current study examines associations between polymorphisms within promoter regions of NFKB1 encoding NF-κB1 and NFKBIA encoding IkappaBalpha (IκBα) with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors. Methodology/Principal Findings: Genetic polymorphisms of NFKB1 and NFKBIA were analyzed by a real-time polymerase chain reaction (real-time PCR) for 462 patients with oral cancer and 520 non-cancer controls. We found that NFKB1 -94 ATGG1/ATGG2, -94 ATGG2/ATGG2, and the combination of -94 ATGG1/ATGG2 and ATGG2/ATGG2 genotypes NFKBIA -826 T (CT+TT) and -881 G (AG+GG) allelic carriages, were more prevalent in OSCC patients than in non-cancer participants. Moreover, we found that NFKB1 or NFKBIA gene polymorphisms seem to be related to susceptibility to develop oral cancer linked to betel nut and tobacco consumption. Finally, patients with oral cancer who had at least one -519 T allele of the NFKBIA gene were at higher risk for developing distant metastasis (P&.05), compared with those patients CC homozygotes. Conclusions: Our results suggest that NFKB1 -94 ATTG2, NFKBIA -826 T, and -881 G alleles are associated with oral carcinogenesis. The combination of NFKB1 or NFKBIA gene polymorphisms and environmental carcinogens appears related to an increased risk of oral cancer. More importantly, the genetic polymorphism of NFKBIA -519 might be a predictive factor for the distal metastasis of OSCC in Taiwanese. ? 2012 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
adenine; cytosine; guanine; I kappa B alpha; immunoglobulin enhancer binding protein; thymine; I kappa B; immunoglobulin enhancer binding protein; NF kappaB inhibitor alpha; NF-kappaB inhibitor alpha; NFKB1 protein, human; adult; allele; article; cancer patient; cancer risk; cancer susceptibility; cigarette smoking; controlled study; distant metastasis; DNA polymorphism; environmental factor; female; gene; genetic association; genetic susceptibility; genotype; heterozygote; high risk patient; homozygote; human; major clinical study; male; mouth carcinoma; Nfkb1 gene; NFKBIA gene; risk assessment; risk factor; squamous cell carcinoma; aged; Areca; Asian; disease predisposition; drinking behavior; genetic polymorphism; genetics; middle aged; mouth tumor; pathology; promoter region; smoking; Taiwan; Nicotiana tabacum; Piper betel; Adult; Aged; Alcohol Drinking; Areca; Asian Continental Ancestry Group; Carcinoma, Squamous Cell; Disease Susceptibility; Female; Genetic Association Studies; Humans; I-kappa B Proteins; Male; Middle Aged; Mouth Neoplasms; NF-kappa B p50 Subunit; Polymorphism, Genetic; Promoter Regions, Genetic; Smoking; Taiwan
Type
journal article