Tae Nam Kim1, Won-Tae Kim2, Mi-So Jeong2, Mi-Hye Mun2, Min-Hye Kim2, Jeong Zoo Lee1, Sun-Hee Leem3. 1. Department of Urology, Medical Research Institute, Pusan National University Hospital, Busan, 49241, South Korea. 2. Department of Biological Sciences, Dong-A University, Busan, 49315, South Korea. 3. Department of Biological Sciences, Dong-A University, Busan, 49315, South Korea. shleem@dau.ac.kr.
Abstract
BACKGROUND: BORIS/CTCFL, a paralog of CTCF and member of the cancer-testicular antigen family, is abnormally activated in multiple cancers. OBJECTIVE: We investigated the relationship between polymorphic variants of the BORIS minisatellite 2 (BORIS-MS2), located within the 5' upstream promoter region of BORIS, and bladder cancer. METHODS: We used case-control study with 516 controls and 113 bladder cancer patients. To evaluate whether minisatellite variants play a role in BORIS expression, we examined the transcript levels of a reporter gene linked to these minisatellites in cell lines. We also examined BORIS expression in cancerous and non-cancerous bladder tissue. RESULTS: A statistically significant association was identified between the short rare allele (13-repeat) and bladder cancer incidence (odds ratio (OR) 2.97, 95% confidence interval (CI) [1.14, 7.74]; P = 0.020). In particular, short rare alleles in the younger group (aged < 65) were associated with statistically significant increase in bladder cancer risk (OR 5.38, CI [1.32, 21.87]; P = 0.01). The BORIS-MS2 region acted as a negative regulator, and the expression level of the luciferase reporter in bladder cancer cells was less effectively inhibited than in normal cells. Furthermore, the expression of BORIS mRNA significantly differed (P < 0.05) between normal and cancerous muscle-invasive bladder cancer tissues, and relationship to clinical parameters was observed. CONCLUSIONS: The short rare allele of BORIS-MS2 could be used to identify bladder cancer risk. BORIS expression levels have been shown to increase with the progression of bladder cancer, could be used as a biomarker for its progression.
BACKGROUND:BORIS/CTCFL, a paralog of CTCF and member of the cancer-testicular antigen family, is abnormally activated in multiple cancers. OBJECTIVE: We investigated the relationship between polymorphic variants of the BORIS minisatellite 2 (BORIS-MS2), located within the 5' upstream promoter region of BORIS, and bladder cancer. METHODS: We used case-control study with 516 controls and 113 bladder cancerpatients. To evaluate whether minisatellite variants play a role in BORIS expression, we examined the transcript levels of a reporter gene linked to these minisatellites in cell lines. We also examined BORIS expression in cancerous and non-cancerous bladder tissue. RESULTS: A statistically significant association was identified between the short rare allele (13-repeat) and bladder cancer incidence (odds ratio (OR) 2.97, 95% confidence interval (CI) [1.14, 7.74]; P = 0.020). In particular, short rare alleles in the younger group (aged < 65) were associated with statistically significant increase in bladder cancer risk (OR 5.38, CI [1.32, 21.87]; P = 0.01). The BORIS-MS2 region acted as a negative regulator, and the expression level of the luciferase reporter in bladder cancer cells was less effectively inhibited than in normal cells. Furthermore, the expression of BORIS mRNA significantly differed (P < 0.05) between normal and cancerous muscle-invasive bladder cancer tissues, and relationship to clinical parameters was observed. CONCLUSIONS: The short rare allele of BORIS-MS2 could be used to identify bladder cancer risk. BORIS expression levels have been shown to increase with the progression of bladder cancer, could be used as a biomarker for its progression.
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