Relationship between EGFR Intron-1 CA SSR 1 polymorphism and skin rash in patients treated with cetuximab.
e22087 Background: EGFR inhibiting drugs do not work equally effectively in cancer patients. We were looking for potential genetic factors which could help to select patients who benefit from treatment with cetuximab. One of established clinical factors is skin rash, which correlate with clinical response to EGFR inhibitors. Our hypothesis was that rash intensity depends on genetic polymorphisms of gene encoding EGFR, especially on Intron-1 CA SSR 1 polymorphism. The number of CA repeats in Intron-1 may affect the level of preRNA synthesis. Methods: The prospective study included 62 patients (colon cancer, head and neck, non-small cell lung cancer and gastric cancer) who were treated with cetuximab together with chemotherapy. 4 weeks after the start of treatment with cetuximab, rash intensity was assessed according to NCI CTAEv.3.0. criteria. DNA for analysis was isolated from 5 ml of peripheral blood. Using the PCR reaction with specific primers (polymorphic DNA segment was amplified. The obtained DNA fragments were analysed by GenScan to determine their lengths. Results: Patients with 15-18 “CA” repetitions were classified as having a short allele “S”, while patients with 19-22 “CA” repetitions have been marked as having a long allele “L”. The relationship between the rash intensity and the CA-polymorphism was assessed (Table). The analysis showed that there is tendency to more intensive rash in patients with pair of “short” alleles (SS), than in patients with “short-long” (SL) and “long” (LL) allelles (p<0,1 chi-square test). Conclusions: There is a relationship between the EGFR Intron-1 CA-polymorphism and the rash intensity in patients treated with cetuximab which warrants further prospective clinical investigation. [Table: see text]