Association of SMAD7 genetic markers and haplotypes with colorectal cancer risk

Abstract

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.

Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer

“…Currently, CEA levels are used as a tool for follow-up observation of patients after treatment rather than to diagnose the tumor itself [ 1 , 2 , 3 , 5 , 16 , 17 ]. A rapid increase in CEA concentration after surgical resection suggests the occurrence of metastases; a slowly increasing level is typical sign of local recurrence [ 18 ].…”

Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer

“…Inactivation of any component in this pathway will result in accelerated cell growth and dysregulation of apoptosis signals, leading to uncontrolled cell growth and differentiation, and the induction of cancer cells[ 66 ]. Therefore, overproduction of SMAD7 leads to significantly decreased EMT in response to TGF-β[ 67 ].…”

Improved two‐step testing of genome‐wide gene–environment interactions

“…One SNP (18:46,458,950:G:A) surpassed the threshold in bin 1. This SNP is located near the SMAD7 gene, which has been previously shown as a potential marker of CRC (Alidoust et al, 2022;Jiang et al, 2013;Stolfi et al, 2014;Thompson et al, 2009). This locus would not have been identified if the Bonferroni correction was used to correct for the number of tests in bin 1 (i.e., using significance threshold = 0.025/3759).…”