Abstract
We studied the predictive value for response and toxicity of functional polymorphisms in genes involved in the oxaliplatin/fluorouracil pathway in colorectal cancer patients. One hundred and twenty-seven (127) patients were treated with curative intended surgery followed by adjuvant chemotherapy with FOLFOX (fluorouracil, leucovorin and oxaliplatin) regimen. The median age was 65.53 (27-80) years (66.9% male, 59.1% rectum). The median follow-up was 8.5 years (IQR, 4.1-9.4). At the end of follow-up, 59 patients (46.5%) had relapsed or died in the whole study population. We did find that XRCC1GG genotype is associated with a higher risk of developing haematologic toxicity. Furthermore, we report a significant association of the TS 3'UTR 6 bp/6 bp polymorphism and the XRCC1 rs25487 with a higher risk of developing anaemia and diarrhoea, respectively. On the other hand, none of the studied polymorphisms showed clinically relevant association with disease-free survival and overall survival or early failure to adjuvant FOLFOX therapy.
Keywords:
Colorectal cancer; adjuvant chemotherapy; personalized medicine; polymorphisms; response; toxicity.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Chemotherapy, Adjuvant
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / surgery
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Endonucleases / genetics
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Endonucleases / metabolism
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Female
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Fluorouracil / administration & dosage
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Fluorouracil / adverse effects
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Fluorouracil / pharmacokinetics
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Humans
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Leucovorin / administration & dosage
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Leucovorin / adverse effects
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Leucovorin / pharmacokinetics
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Male
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Middle Aged
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Neoplasm Staging
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Organoplatinum Compounds / administration & dosage
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Organoplatinum Compounds / adverse effects
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Organoplatinum Compounds / pharmacokinetics
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Oxaliplatin / administration & dosage
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Oxaliplatin / adverse effects
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Oxaliplatin / pharmacokinetics
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Polymorphism, Genetic
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Promoter Regions, Genetic
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Thymidylate Synthase / genetics
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Thymidylate Synthase / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cytoskeletal Proteins
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DNA-Binding Proteins
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ERC2 protein, human
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Organoplatinum Compounds
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Oxaliplatin
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Thymidylate Synthase
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ERCC1 protein, human
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Endonucleases
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Leucovorin
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Fluorouracil