title: c.29C>T polymorphism in the transforming growth factor-β1 (TGFB1) gene correlates with increased risk of urinary bladder cancer.
abstract: TGF-β1 is a pleiotropic cytokine, which plays a dual role in tumor development. In the early stages, it inhibits the growth of tumor while in the late stages of carcinoma, it promotes tumor growth. The purpose of this study was to analyze the distribution of the TGFB1 gene polymorphisms between cases and controls so as to assess their correlation with bladder cancer risk. This study included 237 cases of urinary bladder cancer and 290 age matched controls from the same ethnic background. Three polymorphisms in the TGFB1 gene, c.29C>T (rs-1800470), c.74G>C (rs-1800471) and +140A>G (rs-13447341), were analyzed by direct DNA sequencing. Statistical analyses revealed no significant differences in the demographical data, except that the frequencies of smokers and non-vegetarians were higher in the cases. Eighty percent of the bladder cancer patients had superficial transitional cell carcinoma, and 53.16% and 26.31% of the patients were in grade I and grade II, respectively. We found that c.29C>T substitution increased the risk of bladder cancer significantly and recessive model of analysis was the best fitted model (p=0.004; OR=1.72 95% CI 1.18-2.50). A significantly higher risk in the recessive form was also suggested by co-dominant analysis showing that the homozygous form (TT) was a significant risk factor in comparison to CC and CT genotypes. The other two polymorphisms, c.74G>C (p=0.18, OR=0.67 95% CI 0.37-1.21) and +140A>G (p=0.416, OR=0.77 95% CI 0.41-1.45) did not affect the risk of urinary bladder cancer. In conclusion, we found that the TGFB1 c.29C>T substitution increases the risk of bladder cancer significantly while c.74G>C and +140A>G polymorphisms do not affect the risk.
authors.affiliation: Department of Urology, King George's Medical University, Lucknow, India.
authors.forename: Kirti Amresh
authors.initials: KA
authors.lastname: Gautam
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Pooja
authors.affiliation: Department of Urology, King George's Medical University, Lucknow, India.
authors.forename: Satya Narayan
authors.initials: SN
authors.lastname: Sankhwar
authors.affiliation: Department of Obstetrics & Gynaecology, King George's Medical University, Lucknow, India.
authors.forename: Pushp Lata
authors.initials: PL
authors.lastname: Sankhwar
authors.affiliation: Department of Urology, King George's Medical University, Lucknow, India.
authors.forename: Apul
authors.initials: A
authors.lastname: Goel
authors.affiliation: Endocrinology Division, Central Drug Research Institute, Lucknow, India. Electronic address: rajender_singh@cdri.res.in.
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Single nucleotide polymorphism; Transforming growth factor-β1; Urinary bladder carcinoma