Background: Programmed cell death 6 (PDCD6) is known to be involved in apoptosis and tumorigenesis. Given the reported association with urinary cancer susceptibility through SNP analysis, we further analyzed the entire genomic structure of PDCD6.
Methods: Three VNTR regions (MS1-MS3) were identified through the analysis of the genomic structure of PDCD6. To investigate the association between these VNTR regions and urinary cancer susceptibility, genomic DNA was extracted from 413 cancer-free male controls, 267 bladder cancer patients, and 331 prostate cancer patients. Polymerase chain reaction (PCR) was performed to analyze the PDCD6-MS regions. Statistical analysis was performed to determine the association between specific genotypes and cancer risk. In addition, the effect of specific VNTRs on PDCD6 expression was also confirmed using a reporter vector.
Results: Among the three VNTR regions, MS1 and MS2 exhibited monomorphism, while the MS3 region represented polymorphism, with its transmission to subsequent generations through meiosis substantiating its utility as a DNA typing marker. In a case-control study, the presence of rare alleles within PDCD6-MS3 exhibited significant associations with both bladder cancer (OR = 2.37, 95% CI: 1.33-4.95, P = 0.019) and prostate cancer (OR = 2.11, 95% CI: 1.03-4.36, P = 0.038). Furthermore, through luciferase assays, we validated the impact of the MS3 region on modulating PDCD6 expression.
Conclusions: This study suggests that the PDCD6-MS3 region could serve as a prognostic marker for urinary cancers, specifically bladder cancer and prostate cancer. Moreover, the subdued influence exerted by PDCD6-MS3 on the expression of PDCD6 offers another insight concerning the progression of urinary cancer.
Keywords: PDCD6; Bladder cancer; Polymorphism; Prostate cancer; VNTR.
© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.