PSCArs2294008 T polymorphism increases the risk of bladder cancer in Bai, Dai, and Han ethnicity in China and a potential mechanism

Genes Genomics. 2018 May;40(5):531-541. doi: 10.1007/s13258-018-0653-9. Epub 2018 Feb 3.

Abstract

The aim of this study is to make a comparative evaluation on association of PSCArs2294008 C/T polymorphism with the risk of bladder cancer in Bai, Dai, and Han people in China. A potential mechanism of the T allele risk was also investigated. T allele increased the occurring risk of bladder cancer in Han (OR 1.34; 95% CI 1.17-1.69), Dai, (OR 1.33; 95% CI 1.12-1.70), and Bai (OR 1.14; 95% CI 1.08-1.57) people. T genotype was also observed to associate with invasive bladder cancer in all the three populations (Bai, OR 1.15, 95% CI 1.07-1.87; Dai, OR 1.17, 95% CI 1.05-2.23; Han, OR 1.22, 95% CI 1.10-2.09). PSCA m-RNA levels in T genotype bladder cancer tissues were significantly lower than those in C genotype. An enhancement of PSCA m-RNA level by over-expressing C or T genotype in bladder cancer cells both decreased the cell proliferation and migration, but not affected cell cycle. The increased cell apoptasis due to the over-expression of the two variants was observed. Those change of cell proliferation, migration, and apoptasis was more remarkable in over-expressed C genotype cells than those in over-expressed T genotype. T genotype was genetically high risk to the occurrence of bladder cancer. The decreased PSCA m-RNA levels were involved in the progress of bladder cancer. T allele takes more responsibility for PSCA m-RNA down-regulation to promote cell proliferation and migration and hinder cell apoptasis, thus leading to a higher risk.

Keywords: Bladder cancer; Cell apoptasis; Cell migration; Cell proliferation; Over-expression; PSCA rs2294008 (C/T) polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Apoptosis / genetics
  • Asian People / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • China
  • Ethnicity / genetics
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Urinary Bladder Neoplasms / genetics*

Substances

  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • Neoplasm Proteins
  • PSCA protein, human