Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Gene. 2013 Nov 10;530(2):172-7. doi: 10.1016/j.gene.2013.08.058. Epub 2013 Aug 27.
PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population.
A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case-control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons.
No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25).
These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.
PSCA 是一种组织特异性肿瘤抑制因子或癌基因，已发现其与包括胆囊癌在内的多种人类肿瘤有关。它被认为参与细胞增殖抑制和/或细胞死亡诱导活性。因此，我们旨在研究 PSCA 基因多态性在北印度人群胆囊癌风险中的作用。
本病例对照研究共纳入 405 例胆囊癌患者和 247 例健康对照者进行风险预测。我们通过 Taqman 等位基因鉴别分析检测 PSCA 基因中两个功能性 SNP（rs2294008 和 rs2978974）的关联。使用 SPSS 软件版本 17 进行统计分析。使用 SNPstats 软件进行连锁不平衡和单倍型分析。使用 FDR 检验校正多重比较。
PSCA 基因 rs2294008 和 rs2978974 遗传变异与 GBC 风险在等位基因、基因型或单倍型水平上均无显著相关性。根据胆结石对受试者进行分层也未显示出任何显著结果。然而，在性别分层中，我们发现 rs2294008-Grs2978974 单倍型与女性 GBC 风险增加显著相关（FDR Pcorr=0.021，OR=1.6）。相反，rs2294008-As2978974 单倍型在男性中显著降低风险（FDR Pcorr=0.013；OR=0.25）。
这些发现表明 PSCA 遗传变异可能以性别特异性的方式对 GBC 易感性有显著影响。
