Interleukin-18 gene promoter polymorphisms and the risk of esophageal squamous cell carcinoma.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL-18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to ESCC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and -607 C/A polymorphisms and their haplotypes with the risk of ESCC in a Chinese population.


METHODS
Two hundred and thirty five patients with ESCC and 250 age- and sex-matched controls, using sequence specific primers-polymerase chain reaction (PCR-SSP).


RESULTS
Two polymorphisms, -137 G/C and -607 C/A were in strong linkage disequilibrium (LD). There were significantly differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of ESCC as compared with the -137 GG genotypes (OR = 1.91, 95% CI, 1.29-2.82, p = 0.001 and OR = 2.95, 95% CI, 1.23-7.04, p = 0.012, respectively). Consistent with the results of the genotyping analyses, the -137 C/ -607 A haplotype was associated with a significantly increased risk of ESCC as compared with the -137G/-607 C haplotype (OR = 1.61; 95% CI, 1.16-2.23; p = 0.004).


CONCLUSIONS
This study shows for the first time an association between IL-18 gene promoter -137 G/C polymorphism may contribute represent a genetic risk factor for ESCC in a Chinese population.
Wei
Ye-Sheng
YS
Center of Clinical Laboratory, Affiliated Hospital of Youjiang Medical College for Nationalities, Baise 533000, Guangxi, People's Republic of China. wysh22@163.com
Lan
Yan
Y
Liu
Yun-Guang
YG
Tang
Hui
H
Tang
Ren-Guang
RG
Wang
Jian-Chu
JC
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
D020382:Interleukin-18