Dopamine receptor D2 genetic variations is associated with the risk and clinicopathological variables of urothelial cell carcinoma in a taiwanese population

Min Che Tung, Yu Ching Wen, Shian Shiang Wang, Yung Wei Lin, Yu Cheng Liu, Shun Fa Yang, Ming Hsien Chien

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Abstract

Dopamine receptor D2 (DRD2) is overexpressed in several kinds of cancers and was correlated with the prognosis of these cancers. Polymorphisms within the DRD2 gene were shown to be associated with lung and colon cancers. The purpose of this study was to explore effects of DRD2 gene polymorphisms on the susceptibility to and clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 369 patients diagnosed with UCC and 738 healthy controls were enrolled to analyze DRD2 genotypes at four loci (rs1799732,-141C>del; rs1079597, TaqIB; rs6277, 957C>T; and rs1800497, TaqIA) using a TaqMan-based real-time polymerase chain reaction (PCR). We found a significantly lower risk for UCC in individuals with the DRD2 rs6277 CT genotype compared to those with the wild-type CC genotype (adjusted odds ratio (AOR)=0.405, 95% confidence interval (CI): 0.196~0.837, p=0.015). In 124 younger patients (aged < 65 years) of the recruited UCC cohort, patients who carried at least one T allele of DRD2 rs1800497 were at higher risk (AOR=2.270, 95% CI: 1.060~4.860, p=0.033) of developing an invasive stage (pT2~pT4). In 128 female patients of the recruited UCC cohort, patients who carried at least one deletion allele of DRD2 rs1799732 showed a higher incidence of having an invasive stage (AOR=2.585, 95% CI: 1.066~6.264, p=0.032) and a large tumor (AOR=2.778, 95% CI: 1.146~6.735, p=0.021). Further analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed correlations of the expression of DRD2 with an invasive tumor, tumor metastasis, and the lower survival rate in patients with UCC. Our findings suggest that DRD2 levels might affect the progression of UCC, and the polymorphisms rs6277, rs1800497, and rs1799732 of DRD2 are probably associated with the susceptibility and clinicopathologic development of UCC in a Taiwanese population.

Original languageEnglish
Pages (from-to)1187-1193
Number of pages7
JournalInternational Journal of Medical Sciences
Volume15
Issue number11
DOIs
Publication statusPublished - Jul 30 2018

Fingerprint

Dopamine D2 Receptors
Dopamine Receptors
Carcinoma
Population
Odds Ratio
Confidence Intervals
Neoplasms
Genotype
Alleles
Atlases
Colonic Neoplasms
Genes
Real-Time Polymerase Chain Reaction
Lung Neoplasms
Survival Rate
Genome
Neoplasm Metastasis
Gene Expression
Incidence

Keywords

  • Clinicopathologic development
  • Dopamine receptor D2 gene
  • Polymorphism
  • Susceptibility
  • Urothelial cell carcinoma

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dopamine receptor D2 genetic variations is associated with the risk and clinicopathological variables of urothelial cell carcinoma in a taiwanese population. / Tung, Min Che; Wen, Yu Ching; Wang, Shian Shiang; Lin, Yung Wei; Liu, Yu Cheng; Yang, Shun Fa; Chien, Ming Hsien.

In: International Journal of Medical Sciences, Vol. 15, No. 11, 30.07.2018, p. 1187-1193.

Research output: Contribution to journalArticle

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AU - Yang, Shun Fa

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