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


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.
Gao
Jingfang
J
Department of Oncology, Institute of Biomedicine and Surgery, Linköping University, Linköping, Sweden.
Pfeifer
Daniella
D
He
Lu-Jun
LJ
Qiao
Fang
F
Zhang
Zhiyong
Z
Arbman
Gunnar
G
Wang
Zhen-Lei
ZL
Jia
Cun-Rong
CR
Carstensen
John
J
Sun
Xiao-Feng
XF
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D013548:Sweden / Q000208:ethnology; D044465:White People / Q000235:genetics*
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha