Association of a common genetic variant in prostate stem cell antigen with cancer risk

Introduction: Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general.

Material and methods: To evaluate the role of PSCA rs2294008 (C>T) genotype in global cancer, we performed a pooled analysis of all the available published studies involving 22,817 cancer patients and 27,753 control subjects.

Results: The results showed evidence that PSCA rs2294008 (C>T) was associated with increased total cancer risk in the overall comparisons. Stratified analysis by cancer type indicated that PSCA rs2294008 T is associated with increased risk of gastric cancer (OR = 1.24, 95% CI = 1.09-1.42, p heterogeneity < 0.001, I (2) = 88.0%) and bladder cancer (OR = 1.07, 95% CI = 1.04-1.11, p heterogeneity = 0.108, I (2) = 55.0%) by allelic contrast. Furthermore, in stratified analysis by histological types of gastric cancer, this PSCA variant showed significant associations with diffuse type (OR = 1.81, 95% CI = 1.16-2.81, p heterogeneity < 0.001, I (2) = 88.9%) but not intestinal type (OR = 1.29, 95% CI = 0.95-1.74, p heterogeneity < 0.001, I (2) = 85.2%) in a dominant genetic model. Similar results were found in Asian and European descendents and population-based studies.

Conclusions: In all, our meta-analysis suggests that PSCA rs2294008 (C>T) may play allele-specific roles in cancer development. Further prospective studies with larger numbers of participants worldwide should be performed in different kinds of cancer and other descendents in more detail.