Effect ofRAGEgene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case-control study.
BACKGROUND
To investigate the influence of polymorphisms in the receptor for advanced glycation end products (RAGE) gene and circulating soluble RAGE (sRAGE) levels on susceptibility to gastric cancer, and identify whether these polymorphisms were correlated with serum sRAGE levels.


METHODS
We performed a hospital-based case-control study involving 200 gastric cancer patients and 207 cancer-free controls. Four well-characterizedRAGEgenetic polymorphisms, namely, rs1800624, rs1800625, rs184003, and rs2070600 were genotyped by PCR-RFLP.


RESULTS
The rs2070600 AG genotype might play a predominant role in the development of gastric cancer (adjusted OR 1.62, 95% CI 1.03-2.58). In contrast, the rs184003 GT genotype represented significantly reduced risk for gastric cancer (adjusted OR 0.62, 95% CI 0.39-0.99). Subgroup analysis demonstrated that rs2070600 AG variant genotype enhanced the gastric cancer risk among nonsmokers (OR 1.71, 95% CI 1.01-2.91), nondrinkers (OR 1.75, 95% CI 1.03-2.97), and patients with tumor stage III (OR 2.00, 95% CI 1.13-3.56). The average sRAGE levels in the gastric cancer patients were significantly decreased compared with those of the healthy controls. Subjects carrying the rs2070600 AG genotype had a decreased ability to produce sRAGE. Subjects carrying the rs184003 T variant allele had an increased ability to sRAGE.


CONCLUSIONS
These findings suggested that the variant genotypes of rs184003 and rs2070600 in theRAGEgene exhibit significant associations with gastric cancer risk and circulating sRAGE levels inverse change simultaneously, leading to a marked causal estimate between lowered sRAGE levels and increased gastric cancer risk.
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.
Taijie
T
Li
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.
Weijuan
W
Qin
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.
Yanqiong
Y
Liu
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.
Shan
S
Li
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.
Xue
X
Qin
Department of General Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.
Zhiming
Z
Liu
Gastric cancer; Levels; Polymorphism; RAGE; sRAGE