EGFR, SMAD7, and TGFBR2 Polymorphisms Are Associated with Colorectal Cancer in Patients with Lynch Syndrome

Abstract

Background/aim: Epidermal growth factor receptor (EGFR), mothers against decapentaplegic homolog 7 (SMAD7) and transforming growth factor betta (TGFB) are crucial for colorectal cancer (CRC) tumorigenesis. This study investigated whether polymorphisms in EGFR, SMAD7, and TGFB are associated with CRC risk in patients with Lynch syndrome.

Materials and methods: Genotyping was performed using Sequenom iPLEX MassArray. Association between genetic polymorphisms and CRC was assessed using a weighted Cox proportional hazard model.

Results: Patients carrying the AA genotype of EGFR rs2227983 had a significantly higher CRC risk than those carrying the G allele (HR=2.55, 95% CI=1.25-5.17). The dominant model of SMAD7 rs12953717 (CT + TT genotypes) significantly increased CRC risk (HR=2.17, 95% CI=1.12-4.16) when compared to the wild-type CC genotype. Similarly, the GG genotype of TGFBR2 rs6785358 significantly increased the risk of CRC (HR=21.1, 95% CI=5.06-88.1) compared to the AA genotype.

Conclusion: EGFR, SMAD7, and TGFBR2 are associated with CRC risk in patients with Lynch syndrome.

Keywords: CRC risk; EGFR; Lynch syndrome; SMAD7; TGFB; colorectal cancer; polymorphisms.