Short rare minisatellite variant of BORIS-MS2 is related to bladder cancer susceptibility

• Published in: Genes & genomics Vol. 41; no. 2; pp. 249 - 256
• Main Authors: Kim, Tae Nam, Kim, Won-Tae, Jeong, Mi-So, Mun, Mi-Hye, Kim, Min-Hye, Lee, Jeong Zoo, Leem, Sun-Hee
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.02.2019; Springer Nature B.V; 한국유전학회
• Subjects: Adult; Aged; Alleles; Animal Genetics and Genomics; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Bladder cancer; Cancer; Cell Line, Tumor; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Gene expression; Health risk assessment; HEK293 Cells; Human Genetics; Humans; Invasiveness; Life Sciences; Male; Microbial Genetics and Genomics; Middle Aged; Minisatellite Repeats; Plant Genetics and Genomics; Polymorphism, Genetic; Promoter Regions, Genetic; Reporter gene; Research Article; Statistical analysis; Transcription; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; 생물학; Case-control study; Minisatellite polymorphisms; CTCFL/BORIS; Bladder cancer
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-018-0771-4

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.