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Purpose Colorectal cancer (CRC) is one of the common cancers with a high mortality rate worldwide. In Iran, there has been a trend of increased incidence of colorectal cancer in the last three decades that necessitates the early diagnosis. Genetic factors have an influential role in its etiology along with the conventional risk factors such as age, diet, and lifestyle. Results from GWAS have shown significant associations between  SMAD7  gene variants and risk of CRC. This study aimed to assess the association of certain polymorphisms as well as haplotypes of this gene and risk of colorectal cancer. Methods and materials This study was designed as a case–control association study. After obtaining ethical approval and informed consent, blood samples from 209 patients with colorectal cancer were collected and DNA was extracted. Four variants:  rs4939827 ,  rs34007497 ,  rs8085824  and  rs8088297  were genotyped using ARMS-PCR method. Results SMAD7 rs4939827  in the recessive and co-dominant models was associated with colorectal cancer risk [TT/CT + CC: OR = 2.90, 95%CI (1.38–6.09),  p  = 0.005; CC + TT/CT: OR = 1.66, 95%CI (1.00–2.75),  p  = 0.01]. Haplotype analysis indicated that some SNP combinations including two for-SNPs haplotypes of T-T-C-C and T-C-C-A were significantly associated with CRC risk. Conclusion Based on the identified association of  SMAD7  gene variations and haplotypes with colorectal cancer risk in our population, genetic variations in this gene region may have a role in CRC development. This data may shed light on the genetic predisposition of CRC which involves different pathways including TGF-β.

Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk