Table 1. Common genetic variants from known breast cancer susceptibility loci displaying most significant genome-wide associations with ER-negative breast cancer risk.
| Location | Position | Nearest gene | SNP | Alleles |
iCOGS/GWAS ER-negative |
BRCA1 carriers |
Meta-analysis | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EAF | OR (95% CI) | P | EAF | HR (95% CI) | P | P* | |||||
| Variants in known loci most significantly associated with overall breast cancer | |||||||||||
| †1p36.2 | 10563609 | PEX14 | rs10864459 | G/A | 0.32 | 0.90 (0.87–0.93) | 2.13 × 10−9 | 0.31 | 0.95 (0.91–0.99) | 0.01 | 4.60 × 10−10 |
| †1q32.1 | 202179042 | LGR6 | rs17489300 | A/C | 0.4 | 0.90 (0.87–0.93) | 9.37 × 10−10 | 0.39 | 0.97 (0.93–1.01) | 0.19 | 1.98 × 10−8 |
| 1q32.1 | 204518842 | MDM4 | rs4245739 | A/C | 0.26 | 1.13 (1.11–1.19) | 5.53 × 10−15 | 0.28 | 1.09 (1.05–1.14) | 6.83 × 10−5 | 7.71 × 10−18 |
| 2p24.1 | 19184284 | 2p24.1 | rs12710696 | C/T | 0.36 | 1.10 (1.06–1.13) | 1.70 × 10−8 | 0.39 | 1.01 (0.97–1.05) | 0.56 | 1.90 × 10−6 |
| †2q14.2 | 121088182 | INHBB | rs11903787 | G/A | 0.25 | 0.90 (0.86–0.94) | 8.57 × 10−7 | 0.26 | 0.91 (0.87–0.96) | 2.0 × 10−4 | 7.24 × 10−10 |
| †5p15.3 | 1280028 | TERT | rs2242652 | A/G | 0.20 | 1.18 (1.13–1.23) | 2.73 × 10−14 | 0.22 | 1.22 (1.16–1.28) | 2.53 × 10−15 | 7.58 × 10−28 |
| 5p15.3 | 1282319 | TERT | rs7726159 | A/C | 0.34 | 1.09 (1.05–1.13) | 2.19 × 10−6 | 0.35 | 1.07 (1.02–1.11) | 1.79 × 10−3 | 3.31 × 10−8 |
| 5p15.3 | 1297488 | TERT | rs2736108 | T/C | 0.29 | 0.89 (0.86–0.93) | 1.41 × 10−8 | 0.29 | 0.89 (0.86–0.93) | 4.05 × 10−7 | 3.05 × 10−14 |
| 6q25.1 | 151918856 | ESR1 | rs12662670 | T/G | 0.08 | 1.20 (1.18–1.32) | 8.90 × 10−15 | 0.09 | 1.19 (1.11–1.27) | 9.67 × 10−7 | 1.32 × 10−19 |
| †6q25.1 | 151946152 | ESR1 | rs11155804 | A/T | 0.34 | 1.16 (1.12–1.19) | 8.18 × 10−18 | 0.36 | 1.15 (1.11–1.20) | 0.02 | 3.75 × 10−28 |
| 10q21.2 | 64278682 | ZNF365 | rs10995190 | G/A | 0.16 | 0.89 (0.85–0.93) | 3.75 × 10−8 | 0.16 | 0.99 (0.94–1.04) | 0.66 | 8.23 × 10−6 |
| †10q25.2 | 114782803 | TCF7L2 | rs6585202 | T/C | 0.46 | 1.06 (1.04–1.10) | 3.35 × 10−5 | 0.47 | 1.10 (1.05–1.14) | 6.08 × 10−6 | 1.32 × 10−9 |
| †11p15.5 | 1902097 | LSP1 | rs4980383 | C/T | 0.44 | 1.08 (1.05–1.12) | 3.02 × 10−6 | 0.45 | 1.07 (1.03–1.11) | 7.73 × 10−4 | 9.41 × 10−9 |
| †12p11.2 | 28174817 | PTHLH | rs7297051 | C/T | 0.24 | 0.86 (0.83–0.89) | 1.48 × 10−14 | 0.23 | 0.89 (0.85–0.93) | 2.89 × 10−7 | 3.12 × 10−20 |
| 12p11.2 | 28155080 | PTHLH | rs10771399 | A/G | 0.12 | 0.79 (0.78–0.87) | 3.82 × 10−13 | 0.10 | 0.86 (0.80–0.91) | 2.55 × 10−6 | 7.18 × 10−18 |
| †16q12.1 | 52599188 | TO × 3 | rs4784227 | C/T | 0.24 | 1.15 (1.11–1.19) | 1.11 × 10−14 | 0.26 | 1.07 (1.02–1.12) | 4.97 × 10−3 | 6.44 × 10−15 |
| 16q12.2 | 53813367 | FTO | rs17817449 | T/G | 0.41 | 0.91 (0.89–0.95) | 2.83 × 10−7 | 0.41 | 0.95 (0.92–0.99) | 0.02 | 5.26 × 10−8 |
| 16q12.2 | 53855291 | FTO | rs11075995 | T/A | 0.24 | 1.11 (1.07–1.15) | 3.30 × 10−8 | 0.24 | 1.01 (0.97–1.06) | 0.61 | 1.56 × 10−6 |
| 19p13.1 | 17389704 | MERIT40 | rs8170 | G/A | 0.19 | 1.15 (1.11–1.20) | 1.35 × 10−12 | 0.19 | 1.17 (1.11–1.23) | 7.29 × 10−10 | 6.64 × 10−21 |
| †19p13.1 | 17393925 | ADHB8 | rs56069439 | C/A | 0.30 | 1.16 (1.13–1.20) | 8.25 × 10−19 | 0.30 | 1.19 (1.14–1.24) | 1.42 × 10−15 | 1.49 × 10−32 |
CI, confidence interval; EAF, effect allele frequency; ER, oestrogen receptor; GWAS, genome-wide association studies; HR, hazard ratio; OR, odds ratio; 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.
†SNPs with more significant associations with ER-negative disease than known index SNPs from these loci.