Table 7. Association of common genetic polymorphisms with grade 3–4 diarrhoea, mucositis and neutropenia, excluding patients with rare variant DPYD alleles.
| |
Patients with toxicity levels (n) |
P-value from |
|||||
|---|---|---|---|---|---|---|---|
| Polymorphism | Grade 0–2 | Grade 3–4 | Grade 3–4, excluding rare DPYD variants | Fisher's exact test | Regression model | OR (95% CI) | Gene-based regression model |
|
DPYS
rs2669429 | |||||||
| AA | 90 | 21 | 17 | 0.7901 | 0.546 | 1.23 (0.86–1.78) | — |
| AG | 148 | 56 | 44 | ||||
|
GG |
85 |
25 |
18 |
|
|
|
|
|
TYMS
5′-UTR repeats | |||||||
| 2R/2R | 76 | 35 | 27 | 0.2166 | 0.08 | 0.73 (0.52–1.04) | 0.03101 |
| 2R/3R | 157 | 40 | 31 | ||||
| 3R/3R |
93 |
29 |
22 |
|
|
|
|
|
TYMS
5′-UTR | |||||||
| No. of functional USF-binding sites | |||||||
| 1 | 7 | 1 | 1 | 0.5938 | 0.0835 | 0.62 (0.36–1.06) | |
| 2 | 174 | 64 | 47 | ||||
| 3 | 119 | 30 | 24 | ||||
| 4 | 22 | 9 | 8 | ||||
| 5 |
4 |
0 |
0 |
|
|
|
|
|
TYMS
3′-UTR | |||||||
| del/del | 27 | 20 | 15 | 0.1309 | 0.2668 | 0.80 (0.54–1.19) | |
| in/del | 148 | 35 | 30 | ||||
| in/in |
151 |
49 |
35 |
|
|
|
|
|
MTHFR
677C>T | |||||||
| wt/wt | 170 | 57 | 45 | 0.5575 | 0.8115 | 0.95 (0.64–1.41) | 0.9686 |
| wt/mut | 123 | 38 | 28 | ||||
| mut/mut |
33 |
9 |
7 |
|
|
|
|
|
MTHFR
1298A>C | |||||||
| wt/wt | 163 | 50 | 39 | 1 | 0.8568 | 1.04 (0.70–1.52) | |
| wt/mut | 133 | 46 | 35 | ||||
| mut/mut | 30 | 8 | 6 | ||||
Abbreviations: CI=confidence interval; del=deletion; DPYD=dihydropyrimidine dehydrogenase; DPYS=dihydropyrimidinase; mut=mutation; MTHFR=methylene tetrahydrofolate reductase; OR=odds ratio; USF=upstream stimulatory factor; UTR=untranslated region; wt=wild-type.
ORs are shown from the linear regression model.