Table 6.
Associations with grade and lymph node status a
| Affected by subtype, n (MAF) | Low-grade/no nodal involvement | High grade/nodal involvement | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subtype | Sample | SNP | Locus | Position b | Nearby gene | Ref c | Eff d | Reported e | High-grade/node-positive | Low-grade/node-negative | Unknown | Number unaffected (MAF) | HR (95% CI) | P -value | HR (95% CI) | P -value | P het-value f |
| Grade 3 | BRCA1 carriers | rs17651413 | 2q33.1 | 202677054 | KIAA2012 | A | G | No | 2,495 (0.12) | 655 (0.11) | 4,644 (0.13) | 7,454 (0.11) | 1.01 (0.86 to 1.2) | 0.86 | 1.20 (1.12 to 1.29) | 8.4 × 10−7 | 0.08 |
| rs10069690 | 5p15.33 | 1332790 | TERT | G | A | Yes | 2,493 (0.3) | 654 (0.29) | 4,638 (0.3) | 7,449 (0.26) | 1.15 (1.02 to 1.29) | 0.02 | 1.22 (1.16 to 1.29) | 2.4 × 10−13 | 0.39 | ||
| c6_pos151989450 | 6q25.1 | 151989450 | C6orf97 | G | A | Yes | 2,497 (0.11) | 655 (0.08) | 4,645 (0.1) | 7,455 (0.08) | 1.01 (0.83 to 1.24) | 0.91 | 1.31 (1.21 to 1.42) | 2.2 × 10−11 | 0.02 | ||
| rs8100241 | 19p13.11 | 17253894 | ANKLE1 | G | A | Yes | 2,483 (0.48) | 653 (0.52) | 4,622 (0.48) | 7,420 (0.52) | 0.95 (0.86 to 1.05) | 0.36 | 0.82 (0.78 to 0.86) | 2.2 × 10−16 | 0.01 | ||
| BRCA2 carriers | rs45631588 | 10q26 | 123341292 | FGFR2 | A | G | Yes | 839 (0.44) | 813 (0.48) | 2,678 (0.44) | 3,881 (0.39) | 1.36 (1.24 to 1.49) | 7.4 × 10−11 | 1.19 (1.09 to 1.3) | 1.7 × 10−4 | 0.06 | |
| rs35850695 | 16q12.1 | 51131844 | TOX3 | G | A | Yes | 839 (0.32) | 813 (0.3) | 2,678 (0.3) | 3,881 (0.26) | 1.2 (1.09 to 1.33) | 3.0 × 10−4 | 1.31 (1.19 to 1.44) | 4.0 × 10−8 | 0.26 | ||
| Nodes | BRCA1 carriers | rs1498125 | 4q24 | 106412012 | TET2 | A | G | No | 1,103 (0.2) | 2,274 (0.23) | 4,419 (0.22) | 7,455 (0.2) | 1.18 (1.1 to 1.25) | 4.4 × 10−7 | 0.98 (0.89 to 1.09) | 0.74 | 5.7 × 10−3 |
| rs10069690 | 5p15.33 | 1332790 | TERT | G | A | Yes | 1,100 (0.3) | 2,271 (0.29) | 4,414 (0.3) | 7,449 (0.26) | 1.19 (1.12 to 1.26) | 6.2 × 10−9 | 1.24 (1.13 to 1.35) | 2.0 × 10−6 | 0.5 | ||
| rs11743632 | 5q32 | 145389263 | SH3RF2 | G | A | No | 1,103 (0.31) | 2,274 (0.37) | 4,418 (0.36) | 7,453 (0.37) | 1.05 (0.99 to 1.11) | 0.1 | 0.8 (0.74 to 0.87) | 2.3 × 10−7 | 6.9 × 10−7 | ||
| rs9383936 | 6q25.1 | 151986307 | C6orf97 | G | A | Yes | 1,103 (0.11) | 2,274 (0.09) | 4,420 (0.1) | 7,455 (0.08) | 1.16 (1.06 to 1.28) | 1.3 × 10−3 | 1.41 (1.24 to 1.6) | 1.3 × 10−7 | 0.03 | ||
| rs2349485 | 7p22 | 8517481 | NXPH1 | A | C | No | 1,091 (0.37) | 2,249 (0.34) | 4,374 (0.34) | 7,398 (0.37) | 0.87 (0.82 to 0.92) | 8.5 × 10−7 | 0.97 (0.90 to 1.06) | 0.53 | 0.03 | ||
| rs11669059 | 19p13.11 | 17261453 | ANKLE1 | A | G | Yes | 1,103 (0.41) | 2,273 (0.4) | 4,418 (0.39) | 7,452 (0.43) | 0.85 (0.81 to 0.9) | 2.9 × 10−9 | 0.86 (0.80 to 0.93) | 2.6 × 10−4 | 0.81 | ||
| BRCA2 carriers | rs2981578 | 10q26 | 123330301 | FGFR2 | A | G | Yes | 795 (0.44) | 1,047 (0.48) | 2,428 (0.47) | 3,819 (0.52) | 0.87 (0.8 to 0.94) | 7.4 × 10−4 | 0.75 (0.68 to 0.82) | 1.0 × 10−9 | 0.02 | |
| rs35850695 | 16q12.1 | 51131844 | TOX3 | G | A | Yes | 804 (0.31) | 1,068 (0.3) | 2,458 (0.3) | 3,881 (0.26) | 1.22 (1.12 to 1.33) | 8.5 × 10−6 | 1.30 (1.18 to 1.44) | 2.6 × 10−7 | 0.36 | ||
aCI, Confidence interval; HR, Hazard ratio; MAF, Mean allele frequency. Single-nucleotide polymorphisms (SNPs) associated at P <10−6 with high- or low-grade breast tumors and lymph node–positive or lymph node–negative breast cancer are shown. The most strongly associated SNPs from each locus are reported. bPosition in build 36. cReference allele. dEffect allele. eVariant located in previously reported breast cancer susceptibility locus. fP-value for the difference in association between high-grade breast cancer and low-grade breast cancer for grade 3 and for the association with lymph node–positive breast cancer and lymph node–negative breast cancer.