The understanding of how specific genetic variants modify drug action pathways may provide informative blueprints for individualized chemotherapy.
Dr Xifeng Wu and colleagues from Texas examined the impact of a panel of genetic polymorphisms on clinical outcomes in 210 esophageal cancer patients.
Using the Cox proportional hazards model, MTHFR Glu429Ala variant genotypes were associated with improved survival in patients treated with fluorouracil.
The research team found that the 3-year survival rates for patients with the variant genotypes and the wild genotypes were 65% and 46%, respectively.
Joint analysis of 5 polymorphisms in 3 fluorouracil pathway genes showed a trend for reduced recurrence risk.
|The risk of death decreased with a decreasing number of high-risk alleles|
|Journal of Clinical Oncology|
The team also noted a trend for longer recurrence-free survival as the number of adverse alleles decreased.
For patients receiving platinum drugs, the MDR1 C3435T variant allele was associated with reduced recurrence risk and improved survival.
In nucleotide excision repair genes, the researchers observed a trend for a decreasing risk of death with a decreasing number of high-risk alleles.
In base excision repair genes, the variant alleles of XRCC1 Arg399Gln were associated with the absence of pathologic complete response and poor survival.
Dr Wu's team concluded, “Several biologically plausible associations between individual single nucleotide polymorphisms and clinical outcomes were found.”
“The data also strongly suggest that combined pathway-based analysis may provide valuable prognostic markers of clinical outcomes.”