Abstract
BackgroundTo 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.MethodsWe performed a hospital-based case–control study involving 200 gastric cancer patients and 207 cancer-free controls. Four well-characterized RAGE genetic polymorphisms, namely, rs1800624, rs1800625, rs184003, and rs2070600 were genotyped by PCR–RFLP.ResultsThe 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.ConclusionsThese findings suggested that the variant genotypes of rs184003 and rs2070600 in the RAGE gene 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.
Highlights
To investigate the influence of polymorphisms in the receptor for advanced glycation end products (RAGE) gene and circulating soluble RAGE levels on susceptibility to gastric cancer, and identify whether these polymorphisms were correlated with serum sRAGE levels
This study examined the influence of four well-characterized polymorphisms of the RAGE gene on gastric cancer risk and investigated whether these polymorphisms were correlated with serum sRAGE levels in a southwestern Han Chinese population
In conclusion, the current findings demonstrated that RAGE rs2070600 variant genotypes might play a predominant role in the development of gastric cancer
Summary
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. Numerous clinical studies have established a strong association between RAGE expression and the malignant potential of various cancer types, such as gastric cancer [5], prostate cancer [6], gallbladder cancer [7], pancreatic cancer [8], non small cell lung. RAGE polymorphisms may represent potential candidates as causes of various types of cancers. In this regard, several epidemiological studies have investigated the association between the RAGE gene polymorphism and the risk of various cancers, such as hepatocellular carcinoma [13], breast cancer [14], oral cancer [15], colorectal cancer [16], ovarian cancer [17], and lung cancer [18]. Other studies that examined the genetic background of the RAGE gene found that the circulating soluble form of RAGE (sRAGE) was largely determined by RAGE genetic defects [19,20,21]
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