Table 2. Novel associations of common genetic variants with ER-negative breast cancer risk.
|
iCOGS/GWAS ER-negative |
BRCA1 carriers |
Meta-analysis | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Location | Position | Nearest gene | SNP | r2 | Allele | EAF | OR (95% CI) | P* | EAF | HR (95% CI) | P* | P* |
| 2p23.2 | 29119585 | WDR43 | rs67073037 | 0.98 | A/T | 0.24 | 0.92 (0.88–0.95) | 3.20 × 10−6 | 0.20 | 0.92 (0.87–0.96) | 4.58 × 10−4 | 4.76 × 10−9 |
| 2p23.2 | 29160421 | WDR43 | rs6734079 | 0.99 | T/A | 0.23 | 0.92 (0.88–0.95) | 3.99 × 10−6 | 0.20 | 0.92 (0.87–0.96) | 4.55 × 10−4 | 5.50 × 10−9 |
| 2p23.2 | 29120733 | WDR43 | rs4577244 | 1 | C/T | 0.23 | 0.92 (0.89–0.95) | 6.36 × 10−6 | 0.20 | 0.92 (0.88–0.96) | 5.48 × 10−4 | 1.05 × 10−8 |
| 2q33 | 201717014 | CLK1 | rs74943274 | 0.98 | G/A | 0.015 | 1.34 (1.18–1.52) | 5.89 × 10−6 | 0.02 | 1.20 (1.03–1.41) | 0.012 | 6.00 × 10−7 |
| 2q33 | 201733341 | CLK1/PPIL3 | rs188686860 | 0.98 | C/T | 0.016 | 1.36 (1.20–1.53) | 1.16 × 10−6 | 0.02 | 1.22 (1.04–1.42) | 0.012 | 8.34 × 10−8 |
| 2q33 | 201743594 | PPIL3 | rs115635831 | 1 | G/A | 0.015 | 1.36 (1.20–1.54) | 1.07 × 10−6 | 0.02 | 1.21 (1.03–1.41) | 0.018 | 1.26 × 10−7 |
| 2q33 | 201935871 | FAM126B/NDUFB3 | rs114962751 | 1 | T/A | 0.016 | 1.36 (1.20–1.53) | 1.17 × 10−6 | 0.02 | 1.22 (1.05–1.42) | 0.011 | 7.24 × 10−8 |
| 13q22 | 73957681 | KLF5/KLF12 | rs6562760 | 1 | G/A | 0.23 | 0.92 (0.89–0.96) | 1.85 × 10−5 | 0.20 | 0.89 (0.85–0.94) | 2.85 × 10−6 | 4.98 × 10−10 |
| 13q22 | 73960952 | KLF5/KLF12 | rs2181965 | 0.99 | G/A | 0.23 | 0.92 (0.89–0.96) | 2.16 × 10−5 | 0.20 | 0.89 (0.85–0.94) | 2.39 × 10−6 | 5.04 × 10−10 |
| 13q22 | 73964519 | KLF5/KLF12 | rs8002929 | 1 | A/G | 0.23 | 0.93 (0.89–0.96) | 2.52 × 10−5 | 0.20 | 0.89 (0.85–0.94) | 1.71 × 10−6 | 5.35 × 10−10 |
| 13q22 | 73806982 | KLF5/KLF12 | rs12870942 | 0.99 | T/C | 0.32 | 1.09 (1.05–1.13) | 2.71 × 10−7 | 0.30 | 1.06 (1.01–1.10) | 0.01 | 3.75 × 10−8 |
| 13q22 | 73811471 | KLF5/KLF12 | rs17181761 | 0.99 | A/C | 0.32 | 1.09 (1.05–1.12) | 3.44 × 10−7 | 0.30 | 1.06 (1.01–1.10) | 9.29 × 10−3 | 4.23 × 10−8 |
| 13q22 | 73813803 | KLF5/KLF12 | rs9573140 | 1 | A/G | 0.32 | 1.09 (1.05–1.12) | 3.77 × 10−7 | 0.30 | 1.06 (1.01–1.10) | 0.01 | 5.38 × 10−8 |
CI, confidence interval; EAF, Effect allele frequency; ER, oestrogen receptor; GWAS, genome-wide association studies; HR, hazard ratio; OR, odds ratio; r2, imputation accuracy; SNP, single-nucleotide polymorphism.
*P values from iCOGS/BCAC and meta-analysis for ER-negative breast cancer were estimated by z-test. P values for BRCA1 carriers were estimated by a kinship-adjusted retrospective likelihood approach.