Table 2.
Top 5 SNPs ranked by adjusted (for age and gender) p-value for association with grade 2–3 hypertension, diarrhea, dermatologic toxicity, and composite toxicity in the TARGET study (discovery set) under an additive genetic model.
| SNP | Chr | Gene | Feature | Base change | MAF | grade 2–3 OR (95% CI) | grade 2–3 p-value | grade 3 OR (95% CI) | grade 3 p-value |
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| Hypertension | |||||||||
|
| |||||||||
| rs444904 | 17 | PIK3R5 | Intron 5 | G>A | 0.14 | 3.88 (1.49–10.12) | 0.0056 | 27.30 (3.16–236.20) | 0.0027 |
| rs1346563 | 16 | ADAMTS18 | Intron 3 | C>T | 0.30 | 3.50 (1.43–8.59) | 0.0062 | 5.25 (1.30–21.15) | 0.0197 |
| rs11125039 | 2 | PRKCE | Intron 2 | A>G | 0.24 | 3.49 (1.31–9.25) | 0.0121 | 1.29 (0.31–5.45) | 0.7292 |
| rs2330951 | 7 | EGFR | Intron 1 | A>C | 0.23 | 4.16 (1.37–12.68) | 0.0121 | 5.72 (1.08–30.35) | 0.0404 |
| rs56367980 | 7 | EGFR | Intron 1 | G>A | 0.12 | 3.34 (1.22–9.13) | 0.0185 | 1.66 (0.635–7.99) | 0.5253 |
|
| |||||||||
| Diarrhea | |||||||||
|
| |||||||||
| rs917881 | 7 | EGFR | Intron 1 | G>A | 0.18 | 3.61 (1.68–7.73) | 0.0010 | 3.94 (0.80–19.46) | 0.0921 |
| rs17682789 | 16 | CDH13 | Intron 2 | T>C | 0.31 | 0.27 (0.11–0.64) | 0.0030 | 0.38 (0.08–1.87) | 0.2339 |
| rs11651488 | 17 | MAP2K6 | Intron 1 | T>C | 0.27 | 2.54 (1.30–4.95) | 0.0064 | 2.75 (0.77–9.82) | 0.1186 |
| rs9927200 | 16 | WWOX | Intron 5 | C>A | 0.44 | 2.48 (1.24–4.95) | 0.0099 | 2.64 (0.55–12.61) | 0.2223 |
| rs2716212 | 17 | MAP2K6 | Intron 2 | T>C | 0.42 | 2.25 (1.21–4.18) | 0.0105 | 6.95 (1.32–36.70) | 0.0223 |
|
| |||||||||
| Dermatologic toxicity (HFS + rash or desquamation + pruritus + alopecia) | |||||||||
|
| |||||||||
| rs12366035 | 11 | VEGFB | Exon 5 (syn) | C>T | 0.34 | 2.91 (1.55–5.46) | 0.0009 | 1.94 (0.84–4.50) | 0.1233 |
| rs1868089 | 2 | EPAS1 | Intron 1 | T>C | 0.44 | 2.65 (1.43–4.89) | 0.0020 | 1.80 (0.77–4.21) | 0.1764 |
| rs7557402 | 2 | EPAS1 | Intron 8 | C>G | 0.48 | 2.49 (1.37–4.55) | 0.0029 | 4.35 (1.67–11.37) | 0.0027 |
| rs10958704 | 8 | NA | 2kb up FGFR1 | A>G | 0.36 | 2.06 (1.20–3.56) | 0.0091 | 2.23 (1.03–4.87) | 0.0429 |
| rs12948059 | 17 | MAP2K6 | Intron 1 | A>G | 0.18 | 2.32 (1.22–4.46) | 0.0107 | 2.15 (0.91–5.09) | 0.0816 |
|
| |||||||||
| Composite toxicity | |||||||||
|
| |||||||||
| rs12366035 | 11 | VEGFB | Exon 5 (syn) | C>T | 0.34 | 2.78 (1.54–5.02) | 0.0007 | 1.65 (0.82–3.33) | 0.1637 |
| rs4035887 | 2 | EPAS1 | Intron 1 | G>A | 0.49 | 2.33 (1.36–4.00) | 0.0021 | 1.47 (0.73–2.94) | 0.2779 |
| rs4864950 | 4 | KDR | Intron 29 | T>A | 0.23 | 2.41 (1.29–4.51) | 0.0058 | 1.44 (0.65–3.19) | 0.3626 |
| rs315498 | 17 | NA | RNU6–1134P | T>C | 0.33 | 0.46 (0.26–0.80) | 0.0061 | 0.31 (0.13–0.73) | 0.0076 |
| rs9973653 | 4 | EPAS1 | Intron 1 | G>T | 0.34 | 0.47 (0.27–0.82) | 0.0080 | 0.80 (0.39–1.63) | 0.5326 |
The SNPs in bold are the ones selected for testing in the validation set. Chr: chromosome, CI: confidence interval NA: intergenic SNP, HFS: hand-foot syndrome, MAF: minor allele frequency, OR: odds ratio, SNP: single nucleotide polymorphism, syn: synonymous; up: upstream.