Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia: a case-control and immunohistochemical study

Abstract

BackgroundProstate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence.ResultsNo genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence.ConclusionFrom these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia.

Common Genetic Variants of PSCA, MUC1 and PLCE1 Genes are not Associated with Colorectal Cancer

“…To date, there was only one attempt to associate rs2294008 polymorphisms of PSCA gene with CRC in European subjects. Smith and colleagues performed a study in 388 CRC patients and 496 controls and found no associations of this polymorphism and the risk of CRC (Smith et al, 2012). Our data support the findings of the later study, as rs2294008 and rs2976392 were not related with CRC development.…”

“…Since different cancers may share common pathogenetic pathways (Bunney and Katan, 2006), we hypothesized that SNPs that have been implicated in other gastrointestinal carcinomas may also play a role in CRC development. To date, there are very few papers which have assessed this relationship in CRC patients (Li et al, 2012b;Smith et al, 2012;Wang et al, 2014). Furthermore, to our best knowledge this is the first report aimed at evaluating the role of rs4072037 and rs2274223 for CRC development in European population.…”

“…Currently, there are very few studies analyzing the association between these SNPs and CRC risks. Rs2274223 of PLCE1 gene was found to have protective effect against CRC development in Chinese population (Li et al, 2012c;Wang et al, 2014), but no significant associations were reported for rs4072037 and rs2294008 variants (Li et al, 2012c;Smith et al, 2012). Recent meta-analysis have confirmed the role of these SNPs for the development of different cancers (Hao et al, 2013;Umar et al, 2013;Zheng et al, 2013), outlining the need of studies on CRC patients.…”

PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females

“…Subsequently, it has been demonstrated to be entailed in the pathogenesis of several neoplasms in a tissue/organ specific manner (Smith et al, 2012). PSCA, involving either change in protein expression or through association with the polymorphism in the PSCA gene, may act as an oncogene; play a role in tumor progression in some cancers while tumor suppressor gene in others (Saeki et al, 2010;Smith et al, 2012).…”

“…Subsequently, it has been demonstrated to be entailed in the pathogenesis of several neoplasms in a tissue/organ specific manner (Smith et al, 2012). PSCA, involving either change in protein expression or through association with the polymorphism in the PSCA gene, may act as an oncogene; play a role in tumor progression in some cancers while tumor suppressor gene in others (Saeki et al, 2010;Smith et al, 2012). Genetic variants of PSCA have been found to be strongly associated with the risk for cancers of the breast (Kim et al, 2012), bladder (Rothman et al, 2010), duodenal (Tanikawa et al, 2012) and stomach (Qiao and Feng, 2012) etc.…”