The DNA-polymorphism rs849142 is associated with skin toxicity induced by targeted anti-EGFR therapy using cetuximab

Area of Science:

• Oncology
• Pharmacogenomics
• Dermatology

Background:

• Skin toxicity (ST) is a common adverse effect (AE) of anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC).
• This toxicity impacts patient quality of life and complicates treatment management.
• Predictive biomarkers for ST are needed to personalize anti-EGFR treatment strategies.

Purpose of the Study:

• To identify predictive biomarkers for skin toxicity (ST) in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFR therapy.
• To investigate the association between specific DNA polymorphisms and the occurrence of ST.
• To evaluate the potential of rs849142 as a predictive biomarker for ST.

Main Methods:

• Genotyping of 70 DNA polymorphisms using next-generation sequencing (NGS) in mCRC patients from the FIRE-3 study treated with cetuximab.
• Genotype-phenotype association analysis was performed on a training group (low/high-grade ST) and a validation group (all grades of ST).
• Haplotype analysis was conducted to assess linkage disequilibrium with the identified single nucleotide polymorphism (SNP).

Main Results:

• The single nucleotide polymorphism (SNP) rs849142 showed a significant association with skin toxicity (ST) in both the training (p < 0.01) and validation (p = 0.04) groups.
• rs849142 is located within an intron of the JAZF1 gene.
• Significant linkage disequilibrium was observed between rs849142 and the JAZF1 gene.

Conclusions:

• The DNA polymorphism rs849142 may serve as a predictive biomarker for skin toxicity (ST) in metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR therapy.
• Further validation in larger cohorts is necessary to confirm its clinical utility in managing adverse effects.
• This finding contributes to the development of personalized medicine approaches in mCRC treatment.