Table 2. Validated single nucleotide polymorphisms (SNPs) associated with individual toxicities.
| Toxicity | Treatment group | Lead SNP | Cytoband | Initial GWAS | Validation chemo | Validation cetuximab status | Combined | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR | 95% CI | P-value | P-value | P-value | P-value | |||||||
| Diarrhoea | XELOX + cetuximab | rs6030266 | 20q13.12 | 0.4 | 0.3-0.6 | 5.7 × 10−7 | .33 | 3.6 × 10−2 | 3.2 × 10−7 | |||
| Hand-foot syndrome | FOLFOX | rs1546161 | 1q21.2 | 17.8 | 5.1-62 | 5.9 × 10−6 | .13 | 2.5 × 10−2 | 2.5 × 10−6 | |||
| Neutropenia | FOLFOX + cetuximab | rs9601722 | 13q31.1 | 3.4 | 2.0-5.7 | 5.2 × 10−6 | 3.6 × 10−2 | NA | 3.0 × 10−6 | |||
| Lethargy | XELOX | rs13413764 | 2q14.3 | 1.8 | 1.4-2.3 | 4.5 × 10−6 | NA | 9.2 × 10− 3 | 7.5 × 10−7 | |||
| Nausea | FOLFOX + cetuximab | rs4600090 | 1p33 | 4.0 | 2.2-7.2 | 5.9 × 10−6 | 4.2 × 10−2 | .55 | 4.0 × 10−6 | |||
Abbreviations: CI, confidence intervals; Combined, pooled P-value of initial GWAS cohort and validated cohort (excludes cohort which was not validated); NA, OR in the opposite direction to the initial GWAS; OR, odds ratio; Validation cetuximab status, validation in the COIN and COIN-B group with the alternative chemotherapy regimen but with the same cetuximab status; Validation chemo, validation in the COIN and COIN-B group with the same chemotherapy regimen but alternative cetuximab status.