Polymorphism in the promoter region of the NFKB1 gene increases the risk of sporadic colorectal cancer in Swedish but not in Chinese populations.
OBJECTIVE
An insertion/deletion polymorphism (-94ins/delATTG) in the promoter region of the NFKB1 gene correlates to an increased risk of ulcerative colitis, a known risk factor for colorectal cancer, but this polymorphism has not been studied in colorectal cancer patients. The purpose of this study was to investigate whether this polymorphism is related to colorectal cancer risk and clinicopathological variables.


METHODS
Case samples were taken from four groups of Swedish patients: 193 unselected patients, 90 patients with > or =3 affected 1st-degree relatives, 85 patients with 2 affected 1st-degree relatives, and 109 sporadic cancer patients, and one group of 193 unselected Chinese patients. Controls included 439 Swedish and 458 Chinese healthy individuals. Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism.


RESULTS
The deletion increased the risk of colorectal cancer among Swedish unselected patients (OR =3.81, 95% CI: 2.17-6.69, p <0.0001 for heterozygote deletion, and OR=4.65, 95% CI: 2.43-8.89, p <0.0001 for homozygote deletion) and sporadic cancer patients (OR =7.73, 95% CI: 3.06-19.57, p <0.0001 for heterozygote deletion, and OR =6.58, 95% CI: 2.35-18.43, p <0.0001 for homozygote deletion) compared to homozygote insertion (wild-type), but not among the other Swedish or Chinese patients (p >0.05). Similar evidence was seen in age-adjusted analyses (p <0.0001). The polymorphism did not correlate to clinicopathological variables (p >0.05).


CONCLUSIONS
Deletion of the polymorphism was associated with increased susceptibility to sporadic colorectal cancers in the Swedish population, but not in the Swedish patients with a family history of colorectal cancer or in Chinese patients.
Lewander
Andreas
A
Department of Oncology, Institute of Biomedicine and Surgery, University of Linköping, Linköping, Sweden.
Butchi
Anil Kumar Reddy
AK
Gao
Jingfang
J
He
Lu-Jun
LJ
Lindblom
Annika
A
Arbman
Gunnar
G
Carstensen
John
J
Zhang
Zhi-Yong
ZY
Sun
Xiao-Feng
XF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013548:Sweden
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human