Table 2.
Results of the association analysis of exome chip variants in trained immunity candidate genes and clinical outcome in patients of the Nijmegen Bladder Cancer Study (NBCS)
| Gene name | NMIBC outcome trait and treatment group | Permutation p value unadjusted for multiple testing | n patients | n SNVs in gene including monomorphic |
n SNVs included in gene-based test |
SNV(s) with p<0.10 (effect allele) for asociated genes | SNV effect allele frequency | Effect allele direction of risk | Gene-based association with NMIBC outcome in BCG- and non-BCG treated NMIBC NBCS patients (n=1306) |
| ATG16L1 | RFS and ≥5 BCG instillations | 0.1454 | 215 | 4 | 3 | ||||
| ATG2B | RFS and ≥5 BCG instillations | 0.0552 | 215 | 19 | 9 | rs3759601 (C), rs201204616 (G) | 0.42, 0.002 | Increase, Increase | no |
| ATG7 | RFS and ≥5 BCG instillations | 0.0518 | 215 | 6 | 3 | rs2606736 (G) | 0.37 | Decrease | no |
| EHMT2 | RFS and ≥5 BCG instillations | 0.9200 | 215 | 5 | 4 | ||||
| HNF1B | RFS and ≥5 BCG instillations | 0.3863 | 215 | 3 | 3 | ||||
| ATG16L1 | RFS and ≥7 BCG instillations | 0.0580 | 137 | 4 | 3 | rs3828309 (C), rs2241880 (G), rs3792109 (T) | 0.49, 0.49, 0.50 | Increase, Increase, Increase | no |
| ATG2B | RFS and ≥7 BCG instillations | 0.1165 | 137 | 19 | 8 | ||||
| ATG7 | RFS and ≥7 BCG instillations | 0.0521 | 137 | 6 | 2 | rs2606736 (G) | 0.38 | Decrease | no |
| EHMT2 | RFS and ≥7 BCG instillations | 0.6743 | 137 | 5 | 4 | ||||
| HNF1B | RFS and ≥7 BCG instillations | 0.0427 | 137 | 3 | 3 | rs7501939 (T), rs4430796 (A) | 0.46, 0.49 | Increase, Decrease | no |
| ATG16L1 | PFS and ≥5 BCG instillations | 0.2317 | 215 | 4 | 3 | ||||
| ATG2B | PFS and ≥5 BCG instillations | 0.0080 | 215 | 19 | 9 | rs3759601 (C) | 0.42 | Increase | no |
| ATG7 | PFS and ≥5 BCG instillations | 0.4691 | 215 | 6 | 3 | ||||
| EHMT2 | PFS and ≥5 BCG instillations | 0.0053 | 215 | 5 | 4 | rs486416 (C) | 0.33 | Decrease | no |
| HNF1B | PFS and ≥5 BCG instillations | 0.4879 | 215 | 3 | 3 | ||||
| ATG16L1 | PFS and ≥7 BCG instillations | 0.3270 | 137 | 4 | 3 | ||||
| ATG2B | PFS and ≥7 BCG instillations | 0.0325 | 137 | 19 | 8 | rs3759601 (C), rs72704878 (T) | 0.42, 0.004 | Increase, Increase | no |
| ATG7 | PFS and ≥7 BCG instillations | 0.3489 | 137 | 6 | 2 | ||||
| EHMT2 | PFS and ≥7 BCG instillations | 0.0005 | 137 | 5 | 4 | rs486416 (C) | 0.34 | Decrease | no |
| HNF1B | PFS and ≥7 BCG instillations | 0.6077 | 137 | 3 | 3 |
Depicted are the trained immunity candidate genes (online supplemental table 5) that showed an unadjusted p<0.06 for any of the four outcome/treatment combinations. Values in bold indicate statistical significance (p<0.05) without multiple testing correction. Statistical significance after multiple testing correction was set at p=0.00043.
NMIBC, non-muscle invasive bladder cancer; PFS, progression-free survival; RFS, recurrence-free survival; SNV, single-nucleotide variant.