Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer.

PURPOSE

This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer.

METHODS

Preoperative DCF (docetaxel, 70 mg/m/day, day 1; cisplatin, 70 mg/m/day, day 1; fluorouracil, 750 mg/m/day, days 1-5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients.

RESULTS

According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027).

CONCLUSIONS

ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.