Polymorphisms in tumor necrosis factor genes and susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high incidence region of North China.
BACKGROUND
We investigated the possible association of the functional polymorphisms in the tumor necrosis factor (TNF) genes with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA).


METHODS
The TNF-alpha-308G/A and TNF-beta+252G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, in 555 cancer patients (291 ESCC and 264 GCA) and 437 healthy controls in a high incidence region of North China.


RESULTS
Among healthy controls, frequencies of the TNF-alpha 1/1, 1/2 and 2/2 genotypes were 89.4%, 9.2% and 1.4% respectively, while frequencies of the TNF-beta B1/B1, B1/B2 and B2/B2 genotypes were 12.6%, 32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-alpha-308G/A and TNF-beta+252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [the age and gender adjusted odds ratio (OR) = 2.04 and 1.91, 95% confidence interval (CI) = 1.04 - 4.43 and 1.14 - 2.60, respectively] and GCA (the age and gender adjusted OR = 2.68 and 2.64, 95% CI = 1.14 - 6.29 and 1.47 - 4.72, respectively) in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-beta B1/B2 and TNF-alpha 1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-beta B2/B2 and TNF-alpha 1/1 genotypes (the age and gender adjusted OR = 0.37 and 0.34, 95% CI = 0.15 - 0.92 and 0.13 - 0.90, respectively).


CONCLUSIONS
Therefore, the TNF-alpha-308G/A and TNF-beta+252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.
Guo
Wei
W
Laboratory of Molecular Biology Hebei Cancer Institute, Hebei Medical University, Shijiazhuang 050011, China.
Wang
Na
N
Li
Yan
Y
Zhang
Jian-Hui
JH
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha