Table 4.
Associations with tumor subtypes a
| Affected by subtype, n (MAF) | Positive | Negative | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subtype | Sample | SNP | Locus | Position b | Nearby gene | Ref c | Eff d | Reported e | Positive | Negative | Unknown | Number unaffected (MAF) | HR (95% CI) | P -value | HR (95% CI) | P -value | P het-value f |
| ER status | BRCA1 carriers | rs10069690 | 5p15.33 | 1332790 | TERT | G | A | Yes | 819 (0.27) | 2,635 (0.3) | 4,331 (0.3) | 7,449 (0.26) | 1.09 (0.98 to 1.22) | 0.09 | 1.24 (1.18 to 1.31) | 2.7 × 10−15 | 0.04 |
| rs2046210 | 6q25.1 | 151990059 | C6orf97 | G | A | Yes | 819 (0.36) | 2,639 (0.39) | 4,338 (0.38) | 7,453 (0.35) | 1.04 (0.94 to 1.15) | 0.42 | 1.2 (1.15 to 1.26) | 2.8 × 10−13 | 0.01 | ||
| rs2811708 | 9p21 | 21963422 | CDKN2A/B | C | A | Yes | 816 (0.24) | 2,634 (0.31) | 4,336 (0.28) | 7,445 (0.28) | 0.82 (0.73 to 0.91) | 2.9 × 10−4 | 1.13 (1.07 to 1.19) | 7.3 × 10−6 | 3.9 × 10−7 | ||
| rs45631579 | 10q26 | 123328965 | FGFR2 | A | G | Yes | 819 (0.48) | 2,639 (0.4) | 4,337 (0.42) | 7,455 (0.41) | 1.29 (1.17 to 1.43) | 2.6 × 10−7 | 0.92 (0.87 to 0.96) | 4.7 × 10−4 | 5.1 × 10−9 | ||
| rs2590275 | 12p12 | 28057334 | PTHLH | G | C | Yes | 819 (0.26) | 2,639 (0.25) | 4,338 (0.26) | 7,454 (0.28) | 0.92 (0.83 to 1.03) | 0.14 | 0.87 (0.82 to 0.92) | 5.3 × 10−7 | 0.34 | ||
| rs2363956 | 19p13.11 | 17255124 | ANKLE1 | C | A | Yes | 819 (0.47) | 2,635 (0.53) | 4,334 (0.52) | 7,447 (0.48) | 0.98 (0.89 to 1.08) | 0.71 | 1.25 (1.19 to 1.31) | 6.4 × 10−20 | 1.6 × 10−5 | ||
| BRCA2 carriers | rs2162540 | 10q26 | 123342126 | FGFR2 | A | G | Yes | 1450 (0.47) | 426 (0.41) | 2,348 (0.44) | 3,783 (0.38) | 1.34 (1.25 to 1.43) | 3.6 × 10−16 | 1.08 (0.94 to 1.23) | 0.27 | 6.1 × 10−3 | |
| rs17271951 | 16q12.1 | 51095541 | TOX3 | A | G | Yes | 1490 (0.32) | 434 (0.28) | 2,397 (0.3) | 3,879 (0.25) | 1.29 (1.2 to 1.39) | 8.4 × 10−12 | 1.14 (0.99 to 1.31) | 0.08 | 0.14 | ||
| PR status | BRCA1 carriers | rs10069690 | 5p15.33 | 1332790 | TERT | G | A | Yes | 662 (0.27) | 2,481 (0.29) | 4,642 (0.3) | 7,449 (0.26) | 1.10 (0.98 to 1.24) | 0.09 | 1.24 (1.17 to 1.3) | 1.3 × 10−14 | 0.11 |
| rs2046210 | 6q25.1 | 151990059 | C6orf97 | G | A | Yes | 662 (0.37) | 2,485 (0.39) | 4,649 (0.38) | 7,453 (0.35) | 1.09 (0.98 to 1.21) | 0.12 | 1.18 (1.13 to 1.24) | 2.0 × 10−11 | 0.19 | ||
| rs45631626 | 10q26 | 123327325 | FGFR2 | G | A | Yes | 662 (0.49) | 2,485 (0.4) | 4,647 (0.42) | 7,455 (0.42) | 1.33 (1.2 to 1.48) | 1.3 × 10−7 | 0.92 (0.88 to 0.97) | 9.6 × 10−4 | 5.3 × 10−9 | ||
| rs2590275 | 12p12 | 28057334 | PTHLH | G | C | Yes | 662 (0.26) | 2,485 (0.25) | 4,649 (0.26) | 7,454 (0.28) | 0.92 (0.82 to 1.03) | 0.16 | 0.87 (0.82 to 0.92) | 8.2 × 10−7 | 0.45 | ||
| rs8100241 | 19p13.11 | 17253894 | ANKLE1 | G | A | Yes | 657 (0.51) | 2,473 (0.47) | 4,628 (0.48) | 7,420 (0.52) | 0.98 (0.88 to 1.09) | 0.71 | 0.81 (0.78 to 0.85) | 1.8 × 10−17 | 2.4 × 10−3 | ||
| BRCA2 carriers | rs10017576 | 4q28.3 | 139799629 | G | A | No | 1099 (0.38) | 591 (0.43) | 2,639 (0.41) | 3,880 (0.43) | 0.83 (0.77 to 0.89) | 8.9 × 10−7 | 1.02 (0.92 to 1.14) | 0.67 | 2.7 × 10−3 | ||
| rs4376461 | 8p12 | 32822117 | NRG1 | C | A | No | 1099 (0.15) | 591 (0.10) | 2,640 (0.14) | 3,881 (0.15) | 1.00 (0.9 to 1.12) | 0.93 | 0.6 (0.5 to 0.73) | 2.4 × 10−7 | 1.4 × 10−5 | ||
| rs45631588 | 10q26 | 123341292 | FGFR2 | A | G | Yes | 1099 (0.47) | 591 (0.43) | 2,640 (0.45) | 3,881 (0.39) | 1.33 (1.23 to 1.44) | 2.7 × 10−13 | 1.15 (1.03 to 1.28) | 0.01 | 0.04 | ||
| rs17271951 | 16q12.1 | 51095541 | TOX3 | A | G | Yes | 1099 (0.32) | 591 (0.28) | 2,631 (0.3) | 3,879 (0.25) | 1.32 (1.21 to 1.43) | 4.3 × 10−11 | 1.14 (1.01 to 1.29) | 0.03 | 0.07 | ||
| HER2 status | BRCA1 carriers | rs17008885 | 2p13.2 | 73303647 | SMYD5 | T | A | No | 182 (0.19) | 1,816 (0.3) | 5,799 (0.3) | 7,455 (0.31) | 0.54 (0.43 to 0.69) | 7.8 × 10−7 | 0.99 (0.95 to 1.04) | 0.78 | 3.8 × 10−6 |
| rs10069690 | 5p15.33 | 1332790 | TERT | G | A | Yes | 181 (0.23) | 1,813 (0.29) | 5,791 (0.3) | 7,449 (0.26) | 0.9 (0.71 to 1.13) | 0.36 | 1.24 (1.18 to 1.3) | 3.4 × 10−17 | 0.01 | ||
| rs2046210 | 6q25.1 | 151990059 | C6orf97 | G | A | Yes | 182 (0.39) | 1,816 (0.4) | 5,798 (0.38) | 7,453 (0.35) | 1.12 (0.91 to 1.38) | 0.29 | 1.17 (1.11 to 1.22) | 1.5 × 10−10 | 0.71 | ||
| rs10843055 | 12p12 | 28063088 | PTHLH | A | C | Yes | 171 (0.06) | 1,743 (0.06) | 5,615 (0.06) | 7,234 (0.07) | 0.79 (0.52 to 1.2) | 0.26 | 0.79 (0.72 to 0.87) | 6.2 × 10−7 | 0.99 | ||
| rs4808616 | 19p13.11 | 17264033 | ANKLE1 | C | A | Yes | 176 (0.35) | 1,782 (0.32) | 5,706 (0.32) | 7,339 (0.28) | 1.37 (1.11 to 1.69) | 3.8 × 10−3 | 1.2 (1.14 to 1.26) | 6.8 × 10−13 | 0.25 | ||
| BRCA2 carriers | rs4305889 | 8q12.1 | 60352785 | TOX | A | G | No | 121 (0.18) | 845 (0.09) | 3,353 (0.11) | 3,874 (0.1) | 2.04 (1.53 to 2.71) | 8.7 × 10−7 | 0.96 (0.85 to 1.08) | 0.47 | 1.0 × 10−5 | |
| rs45631588 | 10q26 | 123341292 | FGFR2 | A | G | Yes | 121 (0.45) | 847 (0.46) | 3,362 (0.45) | 3,881 (0.39) | 1.27 (0.98 to 1.63) | 0.07 | 1.28 (1.19 to 1.37) | 2.1 × 10−12 | 0.95 | ||
| rs3817197 | 11p15.5 | 1862750 | LSP1 | G | A | Yes | 121 (0.55) | 847 (0.44) | 3,353 (0.45) | 3,877 (0.47) | 1.30 (1.02 to 1.64) | 0.03 | 0.84 (0.79 to 0.9) | 9.1 × 10−7 | 1.3 × 10−3 | ||
| rs17271951 | 16q12.1 | 51095541 | TOX3 | A | G | Yes | 121 (0.29) | 847 (0.31) | 3,353 (0.3) | 3,879 (0.25) | 1.10 (0.85 to 1.41) | 0.47 | 1.27 (1.18 to 1.37) | 6.9 × 10−11 | 0.3 | ||
| Triple-negativeg | BRCA1 carriers | rs10069690 | 5p15.33 | 1332790 | TERT | G | A | Yes | 579 (0.27) | 1,307 (0.3) | 5,899 (0.3) | 7,449 (0.26) | 1.06 (0.94 to 1.19) | 0.34 | 1.27 (1.2 to 1.36) | 5.2 × 10−14 | 0.02 |
| rs2046210 | 6q25.1 | 151990059 | C6orf97 | G | A | Yes | 580 (0.37) | 1,310 (0.41) | 5,906 (0.38) | 7,453 (0.35) | 1.01 (0.91 to 1.13) | 0.79 | 1.23 (1.16 to 1.31) | 5.5 × 10−12 | 6.8 × 10−3 | ||
| rs9512729 | 13q12.2 | 26974865 | LNX2 | G | A | No | 580 (0.34) | 1,309 (0.43) | 5,902 (0.41) | 7,454 (0.41) | 0.76 (0.69 to 0.85) | 9.1 × 10−7 | 1.08 (1.02 to 1.15) | 0.01 | 1.2 × 10−6 | ||
| rs8100241 | 19p13.11 | 17253894 | ANKLE1 | G | A | Yes | 577 (0.5) | 1,304 (0.46) | 5,877 (0.48) | 7,420 (0.52) | 0.94 (0.85 to 1.04) | 0.22 | 0.81 (0.76 to 0.86) | 2.4 × 10−13 | 0.03 | ||
| BRCA2 carriers | rs2162540 | 10q26 | 123342126 | FGFR2 | A | G | Yes | 735 (0.46) | 133 (0.36) | 3,356 (0.44) | 3,783 (0.38) | 1.39 (1.29 to 1.49) | 9.8 × 10−20 | 0.83 (0.67 to 1.03) | 0.10 | 4.0 × 10−5 | |
| rs1362548 | 16q12.1 | 51121452 | TOX3 | C | G | Yes | 760 (0.32) | 136 (0.29) | 3,434 (0.31) | 3,881 (0.26) | 1.26 (1.17 to 1.36) | 1.0 × 10−9 | 1.18 (0.94 to 1.49) | 0.16 | 0.63 | ||
aCI, Confidence interval; HR, Hazard ratio; MAF, Mean allele frequency. Single-nucleotide polymorphisms (SNPs) associated at P <10−6 with breast cancer by tumor estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status or triple-negative (negative for ER, PR and HER2) are shown. The most strongly associated SNP from each locus is 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 subtype positive and subtype negative breast cancer (for example, ER-positive vs ER-negative). gNon–triple negative was considered as “positive” and triple-negative as “negative.”