Pharmacogenetics in oncology

The number of studies reporting a relationship between DNA sequence variants and cancer treatment outcome is increasing. In particular, the following associations were found: dihydropyrimidine dehydrogenase (DPD) gene mutations and severe 5-FU toxicity, epidermal growth factor receptor mutations (EGFR) and responsiveness of NSCLC to gefitinib, ERCC1 polymorphisms and activity of cisplatin, genetic variants of UGT1A1 gene and severe neutropenia by irinotecan, thymidylate synthase (TS) gene polymorphisms and 5-FU sensitivity, and cytidine deaminase (CDA) genotype and expression of equilibrative nucleoside transporter-1 (hENT1) and response to gemcitabine. The next step in pharmacogenetic research should be the validation of these findings in randomised prospective trials, specifically designed to compare the outcome of treatment selected on the basis of patient's genotype versus standard approach. In conclusion, the improvement in genotyping technologies, combined with efficient and cost-effective analytical methods, may fulfil the promise of personalising the treatment offered to cancer patients.