Investigation of the Roles of MTHFR (C677T and A1298C) and MMP-2 (-1306C>T ) Variations in Bladder Cancer Development.

Objective: Bladder cancer is a complex malignancy and has been associated with high morbidity. Since susceptibility to bladder cancer development differs between individuals, determining the roles of MTHFR and MMP-2 gene variations associated with this cancer is important for analyzing differences in individual susceptibility. In this study, we aimed to investigate the role of MTHFR and MMP-2 gene variations in the development of bladder cancer in the Thrace region of Turkey.

Materials and methods: One hundred seventy-nine blood samples were collected, including 98 patients with bladder cancer and 81 healthy controls. DNA extraction was carried out with blood samples. Polymerase chain reaction-restriction fragment length polymorphism was applied to detect MTHFR C677T (rs 1801133), MTHFR A1298C (rs 1801131), and MMP-2 (-1306C>T) (rs 243865) gene variants.

Results: For the MTHFR A1298C gene variation, CC genotype was the genetic risk factor (P=.0001), while AC genotype was the protective factor (P< .0001) in the development of bladder cancer. For the MMP-2 (-1306C>T) gene variation, TT genotype (P < .0001) and T allele (P=.0006) were genetic risk factors, while AC genotype (P=.0009) was the protective factor in the development of bladder cancer. For C677T/A1298C gene variations, CC-CC combined genotype was the genetic risk factor (P=.009), while CT-AC and CC-AC combined genotypes were potential protective biomarkers (P=.013 and P < .001, respectively).

Conclusion: In our study, TT genotype and T allele were determined as genetic risk factors for MMP-2 (-1306C>T) gene variation. For C677T/A1298C gene variations, CC- CC combined genotype was detected as the genetic risk factor in the development of bladder cancer.