strong association of a common dihydropyrimidine dehydrogenase gene polymorphism with fluoropyrimidine-related toxicity in cancer patients强大的协会共同dihydropyrimidine脱氢酶基因多态性与fluoropyrimidine-related毒性在癌症患者.pdfVIP

Strong Association of a Common Dihydropyrimidine Dehydrogenase Gene Polymorphism with Fluoropyrimidine-Related Toxicity in Cancer Patients 1 2 3¤ 1 1 Eva Gross *, Birgit Busse , Matthias Riemenschneider , Steffi Neubauer , Katharina Seck , Hanns-Georg 2 1 4 1 Klein , Marion Kiechle , Florian Lordick , Alfons Meindl ¨ ¨ ¨ 1 Department of Gynecology, Klinikum rechts der Isar, Technische Universitat Munchen, Munchen, Germany, 2 Center of Human Genetics and Laboratory Medicine, ¨ ¨ ¨ Martinsried, Germany, 3 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universitat Munchen, Munchen, Germany, 4 Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg, Germany Abstract Background: Cancer patients carrying mutations in the dihydropyrimidine dehydrogenase gene (DPYD) have a high risk to experience severe drug-adverse effects following chemotherapy with fluoropyrimidine drugs such as 5-fluorouracil (5-FU) or capecitabine. The pretreatment detection of this impairment of pyrimidine catabolism could prevent serious, potentially lethal side effects. As known deleterious mutations explain only a limited proportion of the drug-adverse events, we systematically searched for additional DPYD variations associated with enhanced drug toxicity. Methodology/Principal Findings: We performed a whole gene approach covering the entire coding region and compared DPYD