Table IV.
Association of single-nucleotide polymorphisms with reduced ovarian function and chemotherapy in the meta-analyses.
| Replication (PCL+SJLIFE) meta-analysis |
Discovery + Replication (VEVO + PCL + SJLIFE) meta-analysis |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Variant | Ref>Alt | Model | variant, interaction | OR (95% CI) | Direction | P-value | OR (95% CI) | Direction | P-value |
| BRSK1 | rs11668344 | A>G | 2 | rs11668344 | 0.82 (0.54–1.24) | −+ | 0.349 | 0.76 (0.53–1.11) | −−+ | 0.152 |
| CED: 0 | 1 (ref) | 5.5 × 10−4 | 1 (ref) | 5.6 × 10−4 | ||||||
| ‒ >0–4000 | 0.58 (0.21–1.58) | −− | 0.284 | 0.98 (0.46–2.09) | +−− | 0.964 | ||||
| ‒ ≥4000–8000 | 3.42 (1.52–7.67) | ++ | 2.8 × 10−4 | 3.83 (1.90–7.74) | +++ | 1.8 × 10−4 | ||||
| ‒ ≥8000 | 1.77 (0.18–17.60) | +− | 0.627 | 1.82 (0.40–8.34) | ++− | 0.442 | ||||
| SNP*CED: 0 | 1 (ref) | 0.016 | 1 (ref) | 0.018 | ||||||
| ‒ >0–4000 | 3.27 (1.11–9.66) | +− | 0.032 | 1.37 (0.29–6.51) | −+− | 0.690 | ||||
| ‒ ≥4000–8000 | 1.04 (0.44–2.48) | +− | 0.922 | 0.98 (0.48–2.02) | −+− | 0.960 | ||||
| ‒ ≥8000 | 3.63 (1.66–7.95) | ++ | 1.3 × 10−3 | 3.81 (1.85–7.86) | +++ | 3.0 × 10−4 | ||||
| FANCI | rs1054875 | A>T | 2 | rs1054875 | 1.01 (0.65–1.56) | +− | 0.977 | 0.85 (0.57–1.28) | −+− | 0.432 |
| CED: 0 | 1 (ref) | 0.002 | 1 (ref) | 2.0 × 10−4 | ||||||
| ‒ >0–4000 | 0.88 (0.28–2.80) | +− | 0.828 | 0.54 (0.23–1.24) | −+− | 0.148 | ||||
| ‒ ≥4000–8000 | 5.29 (2.08–13.50) | ++ | 4.7 × 10−4 | 3.91 (1.83–8.33) | +++ | 4.1 × 10−4 | ||||
| ‒ ≥8000 | 3.69 (0.37–36.8) | ++ | 0.266 | 3.70 (0.83–16.6) | +++ | 0.088 | ||||
| SNP*CED: 0 | 1 (ref) | 0.869 | 1 (ref) | 0.146 | ||||||
| ‒ >0–4000 | 1.35 (0.46–3.96) | ++ | 0.583 | 2.76 (1.17–6.53) | +++ | 0.021 | ||||
| ‒ ≥4000–8000 | 0.64 (0.29–1.40) | −− | 0.264 | 0.92 (0.46–1.86) | +−− | 0.823 | ||||
| ‒ ≥8000 | 1.03 (0.53–2.03) | ++ | 0.925 | 1.14 (0.61–2.12) | +++ | 0.691 | ||||
PCL, PanCareLIFE cohort; SJLIFE, St. Jude Lifetime Cohort.
Model 2: adjusted for principal components, hormone use (only for VEVO, SJLIFE) and CED−categories and the interaction term of variant*CED category. + = positive association of the SNP with reduced ovarian function in PCL and SJLIFE respectively. − = negative association of the SNP with reduced ovarian function in VEVO, PCL and SJLIFE, respectively.