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      Gender-specific genomic profiling in metastatic colorectal cancer patients treated with 5-fluorouracil and oxaliplatin.

      Pharmacogenetics
      Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, administration & dosage, adverse effects, therapeutic use, Colorectal Neoplasms, drug therapy, genetics, pathology, Disease-Free Survival, Female, Fluorouracil, Gene Expression Profiling, Genotype, Humans, Male, Middle Aged, Neoplasm Metastasis, Organoplatinum Compounds, Polymerase Chain Reaction, Polymorphism, Genetic, Sex Characteristics

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          Abstract

          Survival and response rates in metastatic colorectal cancer remain poor, despite advances in drug development. There is increasing evidence to suggest that gender-specific differences may contribute to poor clinical outcome. We tested the hypothesis that genomic profiling of metastatic colorectal cancer is dependent on gender. A total of 152 patients with metastatic colorectal cancer who were treated with oxaliplatin and continuous infusion 5-fluorouracil were genotyped for 21 polymorphisms in 13 cancer-related genes by PCR. Classification and regression tree analysis tested for gender-related association of polymorphisms with overall survival, progression-free survival and tumor response. Classification and regression tree analysis of all polymorphisms, age and race resulted in gender-specific predictors of overall survival, progression-free survival and tumor response. Polymorphisms in the following genes were associated with gender-specific clinical outcome: estrogen receptor β, EGF receptor, xeroderma pigmentosum group D, voltage-gated sodium channel and phospholipase A2. Genetic profiling to predict the clinical outcome of patients with metastatic colorectal cancer may depend on gender.

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