Polymorphism in PSCA gene increases risk for non-cardia gastric cancer
MedWire News: Caucasian individuals with a variation at the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene have an increased risk for developing non-cardia gastric cancer and its precursors, suggest study findings.
However, the study also showed that carriage of this gene variation had a reduced risk for developing the proximal cancers gastric cardia cancer, esophageal adenocarcinoma, and esophageal squamous cell carcinoma.
The findings are of importance, given that an association between gastric cancer and the rs2294008 polymorphism of PSCA has been previously reported only in Asian populations.
Paul Lochead (University of Aberdeen, Scotland) and co-investigators performed a genotyping study that included four independent, Caucasian, case-control studies. The studies included a total of 1748 controls and 166 healthy, first-degree relatives of gastric cancer patients (65 Helicobacter pylori-infected, 43 H. pylori-infected with hypochlorhydria and gastric atrophy, and 58 H. pylori-negative), 533 patients with chronic atrophic gastritis, 621 patients with gastric cancer, and 159 patients with esophageal cancer.
Analyses revealed that carrying the risk allele (T) of rs2294008 in PSCA was associated with a significant 1.5- and 1.9-fold increased risk for chronic atrophic gastritis and non-cardia gastric cancer, respectively.
Chronic atrophic gastritis patients carrying the T allele had an increased risk for atrophy and hypochlorhydria, with the T/T genotype conferring a 4.1-fold increased risk in a recessive model, compared with the C/C genotype. Among gastric cancer patients carrying one copy of the T allele, compared with two copies of the C allele, the association was strongest in those with diffuse histological-type compared with intestinal-type, at odds ratios of 2.9 versus 1.6, respectively. The association was strongest among individuals carrying the T/T genotype with intestinal-type gastric cancer, at an OR of 3.7.
No associations were found between rs2294008 and an increased risk for H. pylori infection in any of the studies.
However, individuals carrying one copy of the T allele for rs2294008 were less likely to develop gastric cardia cancer (OR=0.5), esophageal adenocarcinoma (OR=0.5), and esophageal squamous cell carcinoma (OR=0.4) than individuals carrying two copies of the C allele. Similar associations were obtained for the three proximal cancers in dominant models.
"Given that out data implicate PSCA in the development of atrophic gastritis, it is conceivable that PSCA modifies the host inflammatory response to H. pylori infection," write the authors in the journal Gastroenterology.
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By Ingrid Grasmo