IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese.
BACKGROUND
Nuclear factor of kappa B inhibitor alpha (I kappaB alpha) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of I kappaB alpha to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients.


METHODS
A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in I kappaB alpha were analyzed by TaqMan SNP genotyping assay.


RESULTS
Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients.


CONCLUSIONS
I kappaB alpha rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.
Wang
Shiyan
S
Institute of Digestive Disease and Department of Meddicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Tian
Linwei
L
Zeng
Zhirong
Z
Zhang
Mingdong
M
Wu
Kaichun
K
Chen
Minhu
M
Fan
Daiming
D
Hu
Pinjin
P
Sung
Joseph J Y
JJ
Yu
Jun
J
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha