1. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan;
2. Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;
3. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan;
4. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;
5. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan;
6. Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;
7. Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung, Taiwan;
8. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan;
9. Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Melatonin counteracts tumor occurrence and tumor cell progression in several cancer types in vitro and in vivo. It acts predominantly through its melatonin receptor type 1A (MTNR1A), and genetic variations of MTNR1A affect the susceptibility several diseases and cancer. The purpose of this study was to explore the effect of MTNR1A gene polymorphisms on the susceptibility to and clinicopathological characteristics of urothelial cell carcinoma (UCC). We recruited 272 patients with UCC and 272 normal controls to analyze three common single-nucleotide polymorphisms (SNPs) (rs2119882, rs13140012, and rs6553010) of MTNR1A related to cancer risk and clinicopathological relevance according to a TaqMan-based real-time polymerase chain reaction (PCR). We found that these three SNPs of MTNR1A were not associated with UCC susceptibility. However, patients with UCC who had at least one G allele of MTNR1A rs6553010 (in intron 1) were at higher risk (1.768-fold, 95% confidence interval: 1.068~1.849) of developing an invasive stage (p < 0.026), compared to those patients with AA homozygotes. In conclusion, polymorphic genotypes of rs6553010 of MTNR1A might contribute to the ability to predict aggressive phenotypes of UCC. This is the first study to provide insights into risk factors associated with intronic MTNR1A variants in the clinicopathologic development of UCC in Taiwan.
Keywords: Melatonin receptor type 1A, Single-nucleotide polymorphisms, Urothelial cell carcinoma, Clinicopathologic development.