CA-SSR1 Polymorphism in Intron 1 of theEGFRGene in Patients with Malignant Tumors Who Develop Acneiform Rash Associated with the Use of Cetuximab

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Abstract

Background and Objective

Epidermal growth factor receptor (EGFR) inhibitors are not equally effective in all cancer patients. One potential clinical factor that could help in selecting patients who may benefit from treatment with cetuximab is acneiform rash, which correlates with the clinical response to EGFR inhibitors. Some previous studies have suggested that the tendency to develop rash may depend on polymorphisms in the EGFR gene. In this investigation, the association of degree of CA dinucleotide polymorphism with skin rash and cetuximab therapy outcome was examined.

Methods

The study included 60 patients treated with cetuximab. For each patient, the severity of acneiform rash was assessed, and the type of polymorphism was determined by genotyping. Associations between genotypes, the acneiform rash, and response to treatment were determined by using the chi-square test and Spearman's rank correlation. The cutoffs S ≤ 17(CA), L>17(CA), n(CA) ≤ 35, and n(CA) > 35 were tested, as well as the sum of the two allele repetitions.

Results

A correlation was found between body surface area covered by rash and the sum of the two allele repetitions (p = 0.030). No statistically significant relationship between genotype and response to treatment was observed. However, in patients who have had partial remission, we noticed a higher incidence of polymorphism, with less CA dinucleotide repetitions and early onset of rash.

Conclusion

A correlation between genotype and severity of rash was observed. That is, the severity of rash decreased with an increased number of CA repetitions.

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