Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease

• Published in: International journal of cancer Vol. 137; no. 6; pp. 1362 - 1373
• Main Authors: García‐González, María Asunción, Bujanda, Luis, Quintero, Enrique, Santolaria, Santos, Benito, Rafael, Strunk, Mark, Sopeña, Federico, Thomson, Concha, Pérez‐Aisa, Angeles, Nicolás‐Pérez, David, Hijona, Elizabeth, Carrera‐Lasfuentes, Patricia, Piazuelo, Elena, Jiménez, Pilar, Espinel, Jesús, Campo, Rafael, Manzano, Marisa, Geijo, Fernando, Pellise, María, Zaballa, Manuel, González‐Huix, Ferrán, Espinós, Jorge, Titó, Llúcia, Barranco, Luis, Pazo‐Cid, Roberto, Lanas, Angel
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-09-2015
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Antigens, Neoplasm - genetics; Cancer; Case-Control Studies; Confidence intervals; Disease; duodenal ulcer; Duodenal Ulcer - genetics; Duodenal Ulcer - microbiology; Duodenal Ulcer - pathology; European Continental Ancestry Group - genetics; Female; Gastric cancer; Genes; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study - methods; GPI-Linked Proteins - genetics; Helicobacter Infections - genetics; Helicobacter Infections - pathology; Helicobacter pylori; Humans; Infections; Male; Medical prognosis; Medical research; Middle Aged; Neoplasm Proteins - genetics; Odds Ratio; polymorphism; Polymorphism, Genetic - genetics; Prognosis; PSCA; Risk; Risk Factors; Spain; Stomach Neoplasms - genetics; Stomach Neoplasms - microbiology; Stomach Neoplasms - pathology; Ulcers; Young Adult; Spain; polymorphism; Helicobacter pylori; PSCA; gastric cancer; duodenal ulcer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.29500

Two recent genome‐wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection‐related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR‐TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45–15.33] and nonsteroidal anti‐inflammatory drugs (OR: 6.54; 95% CI: 3.19–12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33–0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63–2.34), smoking (OR: 1.93; 95% CI: 1.54–2.61), family history of GC (OR: 2.83; 95% CI: 2.01–3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07–1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12–1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16–1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse‐type GC (hazard ratio: 1.85; 95% CI: 1.12–3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse‐type of GC in Caucasians.
What's new?
Susceptibility to Helicobacter pylori infection‐related disease differs by ethnic group, and there are vast divergences in disease outcome, specifically for duodenal ulcer (DU) and gastric cancer (GC). Those differences may be explained in part by genetic variations, including differences in allele frequencies of rs2294008, a polymorphism of the PSCA gene. In this study of a Spanish Caucasian population, the rs2294008 T allele was found to be associated with increased GC risk, particularly diffuse‐type GC, and with reduced DU risk. A significant link was uncovered between the rs2294008 T allele and worse overall survival in patients with diffuse‐type GC.