In Reply We thank Ciccolini and Milano for their interest in our work. They correctly highlight the increased risk of fluoropyrimidine-induced toxic effects in women, as confirmed in our study. Of note, although the incidence of D949V and V732I according to sex was not provided in our article, the multivariate gene association analysis was adjusted on all relevant clinical variables associated with toxicity, including sex.
Anyway, we did not find any significant sex effect in the incidence of D949V and V732I (P = .79 and .85, respectively). Schwab et al1 had previously reported a strong DPYD gene/sex interaction for DPYD*2A that increased the prediction rate for male patients, heterozygosity for DPYD*2A being associated with increased incidence of toxic effects only in men but not in women. We could not find such a gene/sex interaction for D949V and V732I (interaction P = .82 and .18, respectively).
Boige V, Vincent M, Laurent-Puig P. Women at a Disadvantage in Fluorouracil Treatment—Reply. JAMA Oncol. 2016;2(6):830-831. doi:10.1001/jamaoncol.2016.1089