List of studies addressing the interaction between germline genetic polymorphisms and patient sex in defining the risk of fluoropyrimidines-related toxicity
| Year | Drug | No. of Patients | Gene/SNP Investigated | Main Findings | Reference |
|---|---|---|---|---|---|
| 2008 | 5-FU | 683 (383 M; 300 F) | DPYD, TYMS, MTHFR | A significant interaction was found between sex and DPYD*2A, which resulted much more associated with toxicity in males than females. | Schwab et al., 2008 |
| 2014 | 5-FU | 2594 (1385 M; 1209 F) | DPYD | A greater effect of DPYD*2A (associated with grade ≥3 5FU-toxicities) in males compared with females. | Lee et al., 2014 |
| 2019 | 5-FU | 512 (294 M; 218 F) | TYMS (rs34743033, rs2853542, rs11280056), MTHFR (rs1801133, rs1801131), ERCC1 (rs11615), XRCC1 (rs25487), XRCC3 (rs861539), XPD (rs1799793, rs13181), GSTP1 (rs1695), GSTT1/GSTM1 (deletion +/−), ABCC1 (rs2074087), and ABCC2 (rs3740066, rs1885301, rs4148386). | Interactions were detected on time to grade ≥3 hematologic toxicity (TTH) for rs1801133 and rs1799793, on time to grade ≥3 gastrointestinal toxicity (TTG) for rs13181, and on time to grade ≥2 neurologic toxicity (TTN) for rs11615. rs1799793 GA genotype and A allele shortened TTH in men. In women, the rs11615 CC genotype worsened TTN and rs13181 G allele improved the TTG. | Ruzzo et al., 2019 |
| 2021 | 5-FU/capecitabine | 313 (160 M; 153 F) | TYMS-TSER (rs45445694) polymorphism | TYMS-TSER 3R/2R polymorphism was associated with incidence of adverse events in female cancer patients. | Ioannou et al., 2021 |
| 2021 | 5-FU/capecitabine | 126 (69 M; 57 F) | TYMS-TSER (rs45445694) polymorphism | A higher prevalence of 2R/2R TYMS genotype was reported in female African American patients developing adverse events compared with men. | Khushman et al., 2021 |
| 2022 | 5-FU/capecitabine | 313 (160 M; 153 F) | MTHFR rs1801133 C > T polymorphism | MTHFR rs1801133 polymorphism was associated with fluoropyrimidine dose reduction in female cancer patients. | Ioannou et al., 2022 |
F, females; M, males; R, repeat