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Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer . BACKGROUND Pharmacogenetic markers related to drug metabolism and mechanisms of action could help to better select patients with metastatic colorectal cancer ( mCRC ) for treatment . Genetic interaction analysis is used as a rational tool to study the contribution of polygenic variation in relation to drug response . PATIENTS AND METHODS A selection of 17 polymorphisms in genes encoding drug targets , pathway molecules and detoxification enzymes was analyzed in 279 previously untreated mCRC patients treated with capecitabine , oxaliplatin and bevacizumab ( CAPOX-B ) . Multifactor dimensionality reduction analysis was used to identify a genetic interaction profile for progression-free survival ( PFS ) . RESULTS Median PFS was 10.9 [ 95 % confidence interval ( CI ) 9.4-12.4 ] months . A genetic interaction profile consisting of the TYMS enhancer region and VEGF +405G > C polymorphisms was significantly associated with PFS . Median PFS was 13.3 ( 95 % CI 11.4-15.3 ) and 9.7 ( 95 % CI 7.6-11.8 ) months for the beneficial and unfavorable genetic profiles , respectively , corresponding to a hazards ratio for PFS of 1.58 ( 95 % CI 1.14-2.19 ) . None of the studied polymorphisms were individually associated with PFS . CONCLUSIONS Our results support a genetic interaction between the TYMS enhancer region and VEGF +405G > C polymorphisms as a predictor of the efficacy of CAPOX-B in mCRC patients .
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Intervention_Pharmacological
capecitabine
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Intervention_Pharmacological
oxaliplatin
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Intervention_Pharmacological
bevacizumab ( CAPOX-B )
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Outcome_Physical
pathway molecules
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Outcome_Physical
detoxification enzymes
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Outcome_Mortality
genetic interaction profile for progression-free survival ( PFS )
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Outcome_Mortality
PFS
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Outcome_Physical
genetic interaction profile
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Outcome_Mortality
Median PFS
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Outcome_Physical
genetic profiles
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Outcome_Mortality
PFS
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Outcome_Physical
genetic interaction
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Participant_Condition
metastatic colorectal cancer .
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Participant_Condition
metastatic colorectal cancer ( mCRC )
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Participant_Sample-size
279
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Participant_Condition
previously untreated mCRC
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Participant_Condition
mCRC