Sex-related incidence and outcomes were reported in various
cancers, including
colorectal cancer.
5-Fluorouracil (5-FU) is widely used as an essential chemotherapeutic agent for
colorectal cancer. However, sex-based differences in
5-FU toxicity have yet to be reported in human
cancer cell lines and xenograft mouse models to date. Here, we investigated, for the first time, sex-based differences in
5-FU toxicity using human
colon cancer cell lines, xenograft mouse models, and Korean patients' data. Female-derived
colon cancer cell lines exhibited greater 5-FU-induced cytotoxicity than male-derived
colon cancer cell lines. We established two xenograft mouse models: one with a male-derived human
colon cancer cell line injected into male mice (a male-xenograft model) and another involving a female-derived human
colon cancer cell line injected into female mice (a female xenograft model). Treatment with
5-FU inhibited
tumor growth and led to hematological toxicity in a female xenograft model more potently than in a male xenograft model. We analyzed the data obtained from Korean patients with
colorectal cancer to examine sex differences in
adverse drug reactions caused by
5-FU. Korean female patients with
colorectal cancer who received
5-FU chemotherapy experienced more frequent
adverse drug reactions including
alopecia and
leukopenia than male patients. Taken together, we demonstrated that female may be associated with increased risk of toxicity to
5-FU treatment in
colorectal cancer based on in vitro and in vivo investigations and clinical data analysis. Our study suggests sex as an important clinical factor, which predicts induction of toxicity related to
5-FU treatment.