Variants of SMAD1 gene increase the risk of colorectal cancer in the Bangladeshi population.

ABSTRACT

Colorectal cancer is the fourth most common type of malignancy worldwide that may develop due to the accumulation of several genetic variations. Different single nucleotide polymorphisms of SMAD1 gene are assumed to be linked with increased colorectal cancer risk. The current case-control study was conducted to verify the association of genetic polymorphisms of SMAD1 (rs11100883 and rs7661162) with colorectal cancer in the Bangladeshi population. This study was performed on 275 colorectal cancer patients and 300 healthy volunteers using polymerase chain reaction-restriction fragment length polymorphism method. The odds ratios were adjusted for age and sex with logistic regression analysis. In case of SMAD1 rs11100883 polymorphism, GA heterozygous genotype, GA + AA (dominant model), and minor allele "A" were significantly associated with colorectal cancer (adjusted odds ratio = 1.55, 95% confidence interval = 1.09-2.20, p = 0.014; adjusted odds ratio = 1.59, 95% confidence interval = 1.13-2.23, p = 0.008; and odds ratio = 1.35, 95% confidence interval = 1.06-1.73, p = 0.015, respectively) and the significance exists after the Bonferroni correction. Again, single nucleotide polymorphism rs7661162 showed significant association with an elevated colorectal cancer risk for AG heterozygous genotype, AG + GG (dominant model), AG versus AA + GG (overdominant model), and minor allele "G" (adjusted odds ratio = 1.78, 95% confidence interval = 1.24-2.56, p = 0.002; adjusted odds ratio = 1.68, 95% confidence interval = 1.18-2.39, p = 0.004; adjusted odds ratio = 1.76, 95% confidence interval = 1.23-2.53, p = 0.002; and odds ratio = 1.47, 95% confidence interval = 1.08-2.00, p = 0.014, respectively) and significance withstands after the Bonferroni correction. No significant age and gender differences between cases and controls were observed. In silico, gene expression analysis showed that the SMAD1 mRNA level was downregulated in the colon and rectal cancer tissues compared to healthy tissues. In conclusion, our findings indicate that SMAD1 rs11100883 and rs7661162 polymorphisms are responsible for increasing the susceptibility of colorectal cancer development in the Bangladeshi population.