Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations

Abstract

Objective: The inhibitory proteins, IkappaBs, regulate the activity of nuclear factor kappa-beta (NF-kappaB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IkappaBs may be involved in cancer development through the activation of NF-kappaB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3' UTR of NFKBIA (encoding IkappaBalpha) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients.

Material and methods: A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR-restriction fragment length polymorphism.

Results: The frequency of the AG genotype was increased in the Chinese patients >or=50 years of age compared with the Chinese controls (odds ratio (OR)=3.06, 95% confidence interval (CI)=1.55-6.02, p=0.001), even when adjusted for age (OR=3.20, 95% CI=1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl=1.28-7.60, p=0.01).

Conclusions: Chinese individuals >or=50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients.