Haplotype structure defines effects of common DPYD variants c.85T > C (rs1801265) and c.496A > G (rs2297595) on dihydropyrimidine dehydrogenase activity: Implication for 5-fluorouracil toxicity.

Based on our data, DPYD-c.496A > G is a strong candidate risk allele for 5-FU toxicity. Our data suggest that DPYD-c.85T > C might be protective; however, the deleterious impacts of the linked alleles c.496A > G and c.1129-5923C > G likely limit this effect in patients. The possible protective effect of c.85T > C and linkage disequilibrium with c.496A > G and c.1129-5923C > G may have hampered prior association studies and should be considered in future clinical studies.