Selected associations between genetic variants and capecitabine toxicity in QUASAR2
| Gene | SNP b37 coordinate | Toxicity- associated allele/other allele | TAF | n Genotyped n imputed | Info score A=Hap370 B=Hap610 C=Omni2.5 | Global binary: 012v34 OR (95% CI) p-value | Global quant:01v2v34 OR (95% CI) p-value | HFS binary:012v34 OR (95% CI) p-value | HFS quant:01v2v34 OR (95% CI) p-value | Diarrhoea binary:012v34 OR (95% CI) p-value | Diarrhoea quant:01v2v34 OR (95%CI) p-value | Other clinically actionable associations |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DPYD | rs12132152 chr1:97523004 | A/G | 0.031 | 456 484 | 0.993A | 3.83 (3.26–4.40) | 1.61 (1.41–1.82) | 6.12 (5.48–6.76) | 1.74 (1.53–1.95) | 0.44 (0–1.32) | 0.85 (0.68–1.02) | |
| 4.31×10−6 | 5.89×10−6 | 3.29×10−8 | 1.47×10−7 | 0.065 | 0.068 | |||||||
| DPYD | rs76387818 chr1:97539400 | A/G | 0.031 | 0 940 | 0.993A 0.999B 0.999C | 4.05 (3.47–4.62) | 1.66 (1.45–1.87) | 6.44 (5.79–7.09) | 1.78 (1.57–1.99) | 0.44 (0–1.33) | 0.86 (0.68–1.03) | |
| 2.11×10−6 | 1.93×10−6 | 1.75×10−8 | 5.51×10−8 | 0.071 | 0.083 | |||||||
| DPYD | rs7548189 chr1:97 867 713 | A/C | 0.196 | 940 0 | N/A | 1.67 (1.43–1.91) | 1.23 (1.14–1.31) | 1.42 (1.15–1.69) | 1.16 (1.07–1.25) | 1.21 (0.84–1.58) | 1.18 (1.10–1.25) | Diarrhoea 01v234 1.76 (1.50–2.02) |
| 3.79×10−5 | 6.82×10−6 | 0.011 | 0.0011 | 0.0015 | 1.54×10−5 | 1.72×10−5 | ||||||
| DPYD | rs12 022 243 chr1: 97 862 780 | T/C | 0.196 | 0 940 | 0.996A 0.992B 0.998C | 1.69 (1.45–1.94) | 1.23 (1.14–1.32) | 1.43 (1.16–1.7) | 1.16 (1.07–1.25) | 1.79 (1.54–2.05) | 1.18 (1.11–1.26) | |
| 2.55 x10−5 | 4.45 x10−6 | 0.0096 | 8.26 x10−4 | 9.86 x10−6 | 1.11 x10−5 | |||||||
| TYMS/ENOSF1 | rs2612091 chr18:683 607 | C/T | 0.532 | 940 0 | N/A | 1.59 (1.39–1.79) 5.28×10−6 | 1.19 (0.77–0.91) 2.35×10−6 | 1.57 (0.45–0.83) 2.94×10−6 | 1.21 (0.76–0.90) 3.67×10−7 | 1.18 (0.55–1.15) 0.29 | 1.04 (0.90–1.03) 0.27 | HFS 01v234 1.57 (0.45–0.83) 2.94×10−6 |
| TYMS/ENOSF1 | rs2741171 chr18:700 687 | T/C | 0.534 | 0 940 | 0.960A 0.975B 0.990C | 1.60 (1.39–1.80) 6.64×10−6 | 1.20 (1.13–1.28) 9.24×10−7 | 1.74 (1.51–1.97) 1.64×10−6 | 1.23 (1.16–1.31) 3.10×10−8 | 1.01 (0.70–1.32) 0.92 | 1.03 (0.97–1.09) 0.37 | HFS 01v234 1.61 (1.42–1.80) 1.44×10−6 |
The table shows the results of the meta-analysis of global and selected individual toxicities, measured as binary or continuous (‘quant’) variables, in the two arms of QUASAR2. The frequency of the toxicity-associated allele (TAF) is also shown and ORs are expressed relative to this. Imputation quality Info Score is also shown, as are numbers of samples imputed and directly genotyped. The final column shows results for toxicity phenotype classifications that could lead to treatment change or delay according to the QUASAR2 protocol. There was no evidence of heterogeneity between QUASAR2 arms in any of these analyses Phet>0.2, I2<0.25).