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

Rai, Rajani; Sharma, Kiran; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

doi:10.1016/j.gene.2013.08.058

Cited by 27 publications

(21 citation statements)

References 36 publications

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“…For PSCA meta-analysis, a total of 27 articles ([ 24 , 28 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ] Figure 1 ) were found eligible. Remarkably, the study by Lochhead et al (2011) analyzed the association of rs2294008 polymorphism with GC risk in Poland and USA population, while the EC risk to USA population, and hence these were counted as three different studies [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…rs2294008 C > T and rs2976392 G > A are the most extensively studied SNPs in the PSCA gene shown to be associated with increased risk of bladder and stomach cancer [ 22 , 23 ]. However, in our previous study, we failed to find an association between rs2294008 SNP and gallbladder cancer risk [ 24 ]. A number of studies have also investigated the association of these SNPs with various cancer susceptibility, though the results are discrepant as the PSCA gene function in a tissue/organ specific manner, i.e.…”

Section: Introductionmentioning

confidence: 94%

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Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population

Chandra

Kim

Gupta

et al. 2016

Genes

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Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p ≤ 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p ≤ 0.0001; AA vs. GG + GA; OR = 1.52, p ≤ 0.004, A vs. G allele: OR = 1.41, p ≤ 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p ≤ 0.0001; CT + TT vs. CC: OR = 1.24, p ≤ 0.0001; TT vs. CC + CT; OR = 1.17, p ≤ 0.005, T vs. C allele: OR = 1.16, p ≤ 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population

Chandra

Kim

Gupta

et al. 2016

Genes

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“…The studied cancer type included gastric cancer [8, 14-17, 20-22, 25, 26, 31, 32, 34, 39, 41-43], bladder cancer [9, 18, 23, 28, 35, 40], prostate cancer [19], esophageal cancer [20, 33], breast cancer [24], colorectal cancer [27], and gallbladder cancer [29, 30]. In term of ethnicity, 21 studies were performed among Asians, 10 studies among Caucasians, and one study among Africans.…”

Section: Resultsmentioning

confidence: 99%

PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies

Dai

Hua

et al. 2015

Genes Cancer

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PSCA gene plays an important role in cell adhesion, proliferation and survival.Increasing studies have focused on the association of PSCA gene rs2294008 C>T and rs2976392 G>A with cancer risk. However, the conclusions were inconsistent. Therefore, we performed a meta-analysis to elucidate whether there is a true association, or artifact. We systematically searched eligible studies from MEDLINE, EMBASE and CBM database. Odds ratios and 95% confidence intervals were used to evaluate the strength of the association. The final analysis included 32 studies consisting of 30028 cases and 38765 controls for the rs2294008 C>T polymorphism, and 14 studies with 8190 cases and 7176 controls for the rs2976392 G>A polymorphism. Consequently, the PSCA rs2294008 C>T polymorphism was significantly associated with increased overall cancer risk. Further stratifications indicated the increased risk was more pronounced for gastric (diffused type and non-gastric cardia adenocarcinoma) and bladder cancer. A similar association was observed for the rs2976392 G>A polymorphism. This meta-analysis demonstrated that both of the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms are associated with increased cancer risk, especially for gastric cancer and bladder cancer. Further large-scale studies with different ethnicities and subtypes of gastric cancer are required to confirm the results from this meta-analysis.

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“…The T allele is a risk allele for GC and GBC in which PSCA is down-regulated rs2294008T was previously shown to be associated with GC and GBC (Sakamoto et al 2008;Matsuo et al 2009;Wu et al 2009;Lu et al 2010;Ou et al 2010;Lochhead et al 2011;Song et al 2011;Zeng et al 2011;Sala et al 2012;Rai et al 2013;Saeki et al 2013). In the Japanese and Korean populations, both of which have the highest incidence of GC in the world, T is the major allele, whereas it is a minor allele in other ethnic populations (Sakamoto et al 2008;Song et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…However, down-regulation of the gene was reported in GC and gallbladder cancer (GBC), where it may act as a tumor suppressor (Sakamoto et al 2008;Ono et al 2012). In addition to GC, an association of the T allele of rs2294008 was showed in GBC (Rai et al 2013).…”

Section: Introductionmentioning

confidence: 99%

rs2294008T, a risk allele for gastric and gallbladder cancers, suppresses the PSCA promoter by recruiting the transcription factor YY1

et al. 2015

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Previous genomewide association studies identified prostate stem cell antigen (PSCA) as a gastric cancer (GC) susceptibility gene and showed an association between GC and the T allele of the single nucleotide polymorphism rs2294008 (C/T) in this gene. The protein product of this gene inhibits cell growth, and the T allele significantly suppresses the transcriptional activity of the À3.2 kb PSCA upstream region. However, the mechanism remains unknown. In this study, we conducted reporter assays using the PSCA upstream region containing the C allele and identified the region from À200 to +38 bp of the transcription initiation site of the gene as a critical region of the À3.2 kb PSCA upstream region. We found that introducing the T allele at rs2294008 generated a consensus binding sequence for the Polycomb group transcription factor Yin Yang 1 (YY1) and that disruption of the consensus sequence restored the transcriptional activity to the À3.2 kb PSCA upstream region. These findings imply that the T allele significantly suppresses PSCA expression in vivo by recruiting YY1 to its promoter, which eventually predisposes gastric epithelial cells to GC development.

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

Cited by 27 publications

References 36 publications

Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population

Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population

PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies

rs2294008T, a risk allele for gastric and gallbladder cancers, suppresses the PSCA promoter by recruiting the transcription factor YY1

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