Abstract
Candidate genes involved in DNA repair, 5-fluorouracil metabolism and drug detoxification were genotyped in 124 patients receiving neoadjuvant chemoradiation treatment for locally advanced esophageal cancer and their predictive role for long-term relapse-free survival (RFS) and cancer-specific survival (CSS) were evaluated. A panel including MTHFR 677TT, MDR1 2677GT, GSTP1 114CC, XPC 499CC and XPC 939AC+CC, defined as high-risk genotypes, discriminated subgroups with significantly different outcomes. When the panel was combined with histology, patients split into two subsets with 5-year RFS and CSS rates of 65% vs 27% (hazard ratio (HR) 3.0, P<0.0001) and 69% vs 31% (HR 2.9, P<0.0001), respectively. Combining the 5-single-nucleotide polymorphism (5-SNP) panel with pathological response defined two major informative risk classes with 5-year PFS and CSS rates of 79.4% vs 17.7% (HR 6.71, P<0.0001) and 79.3% vs 26.3% (HR 6.25, P<0.0001), respectively. This classification achieved a sensitivity of 79%, a specificity of 85.4% and an accuracy of 81.8%.
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Acknowledgements
We thank Dr Laura Cestari and Peter Andrews for statistical support. This study was funded by Lega Italiana per la Lotta contro i Tumori (LILT), Italy; PRIN fund, Italy; and CARIPARO Foundation, Italy.
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Gusella, M., Giacopuzzi, S., Bertolaso, L. et al. Genetic prediction of long-term survival after neoadjuvant chemoradiation in locally advanced esophageal cancer. Pharmacogenomics J 17, 252–257 (2017). https://doi.org/10.1038/tpj.2016.9
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DOI: https://doi.org/10.1038/tpj.2016.9
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