Table 1.
Association of rare coding variants with breast cancer, for the 113 DNA repair genes sequenced in the GENESIS population [20]
| Gene | Any variant | ||||
|---|---|---|---|---|---|
| Control carriers | Case carriers | ORa (95% CI) | P value | Groupb | |
| BABAM1/MERIT40 | 4 | 2 | 0.5 (0.1, 2.8) | 0.43 | Low |
| BACH1 | 22 | 21 | 0.8 (0.4, 1.5) | 0.55 | Low |
| BRCC3/BRCC36 | 3 | 1 | 0.3 (0.0, 3.2) | 0.34 | Low |
| BRE | 11 | 7 | 0.6 (0.2, 1.6) | 0.35 | Low |
| CDH1 | 14 | 11 | 0.8 (0.4, 1.7) | 0.54 | Low |
| CDKN1A | 13 | 11 | 0.8 (0.4, 1.9) | 0.66 | Low |
| COBRA1 | 6 | 4 | 0.7 (0.2, 2.4) | 0.55 | Low |
| DLG1 | 25 | 15 | 0.6 (0.3, 1.2) | 0.12 | Low |
| ESR1 | 10 | 6 | 0.6 (0.2, 1.5) | 0.26 | Low |
| EXO1 | 45 | 37 | 0.8 (0.5, 1.3) | 0.41 | Low |
| FAM175A/ABRAXAS | 7 | 5 | 0.7 (0.2, 2.3) | 0.56 | Low |
| FANCA | 19 | 15 | 0.8 (0.4, 1.6) | 0.53 | Low |
| FANCD2 | 20 | 15 | 0.7 (0.4, 1.4) | 0.33 | Low |
| FANCF | 6 | 5 | 0.8 (0.3, 2.8) | 0.77 | Low |
| FANCG | 6 | 4 | 0.7 (0.2, 2.4) | 0.55 | Low |
| FANCI | 22 | 13 | 0.6 (0.3, 1.2) | 0.13 | Low |
| IRS2 | 13 | 9 | 0.7 (0.3, 1.5) | 0.33 | Low |
| KIAA1967 | 22 | 17 | 0.8 (0.4, 1.5) | 0.41 | Low |
| LIG4 | 15 | 13 | 0.7 (0.3, 1.6) | 0.46 | Low |
| MLH3 | 21 | 10 | 0.5 (0.2, 1.0) | 0.06 | Low |
| MUS81 | 10 | 7 | 0.6 (0.2, 1.6) | 0.30 | Low |
| MYC | 2 | 2 | 0.8 (0.1, 5.5) | 0.78 | Low |
| NAT1 | 3 | 1 | 0.4 (0.0, 3.4) | 0.37 | Low |
| PMS2 | 22 | 16 | 0.7 (0.3, 1.3) | 0.24 | Low |
| POLH | 13 | 5 | 0.4 (0.1, 1.1) | 0.07 | Low |
| POLQ | 43 | 36 | 0.8 (0.5, 1.2) | 0.43 | Low |
| PRKAA2 | 8 | 3 | 0.4 (0.1, 1.5) | 0.16 | Low |
| RAD51D/RAD51L3 | 9 | 4 | 0.4 (0.1, 1.4) | 0.17 | Low |
| RAD54L | 21 | 12 | 0.6 (0.3, 1.2) | 0.14 | Low |
| RTEL1 | 20 | 8 | 0.4 (0.2, 0.9) | 0.03 | Low |
| TIMELESS | 28 | 23 | 0.8 (0.5, 1.4) | 0.44 | Low |
| TP53BP1 | 27 | 21 | 0.8 (0.5, 1.5) | 0.51 | Low |
| TP63 | 6 | 3 | 0.5 (0.1, 2.0) | 0.33 | Low |
| TTI2 | 9 | 7 | 0.8 (0.3, 2.2) | 0.67 | Low |
| WDR48 | 15 | 10 | 0.7 (0.3, 1.5) | 0.36 | Low |
| XRCC1 | 31 | 21 | 0.7 (0.4, 1.2) | 0.14 | Low |
| APEX1 | 10 | 10 | 1.0 (0.4, 2.4) | 0.98 | No effect |
| AR | 32 | 31 | 1.0 (0.6, 1.6) | 0.94 | No effect |
| ATR | 30 | 29 | 1.0 (0.6, 1.6) | 0.92 | No effect |
| BAP1 | 4 | 4 | 1.0 (0.3, 4.0) | 1.00 | No effect |
| BLM | 35 | 31 | 0.9 (0.5, 1.4) | 0.59 | No effect |
| CDC27 | 12 | 12 | 1.0 (0.5, 2.3) | 0.98 | No effect |
| CDKN2A | 3 | 3 | 1.0 (0.2, 4.9) | 0.99 | No effect |
| EIF4G1 | 26 | 29 | 1.1 (0.7, 1.9) | 0.67 | No effect |
| EP300 | 21 | 18 | 0.9 (0.5, 1.6) | 0.66 | No effect |
| ERCC6 | 47 | 53 | 1.1 (0.8, 1.7) | 0.55 | No effect |
| FANCB | 9 | 9 | 0.9 (0.4, 2.4) | 0.87 | No effect |
| FANCC | 11 | 10 | 0.9 (0.4, 2.2) | 0.87 | No effect |
| FANCE | 11 | 10 | 0.9 (0.4, 2.2) | 0.86 | No effect |
| FANCL | 9 | 10 | 1.1 (0.4, 2.8) | 0.84 | No effect |
| FLNA | 25 | 24 | 1.0 (0.6, 1.7) | 0.94 | No effect |
| MAGI3 | 26 | 28 | 1.1 (0.6, 1.8) | 0.82 | No effect |
| MAST2 | 46 | 50 | 1.1 (0.7, 1.7) | 0.66 | No effect |
| MCM4 | 25 | 29 | 1.1 (0.7, 1.9) | 0.70 | No effect |
| MCPH1 | 27 | 28 | 1.0 (0.6, 1.8) | 0.92 | No effect |
| MDC1 | 24 | 22 | 0.9 (0.5, 1.7) | 0.81 | No effect |
| MSH2 | 18 | 17 | 0.9 (0.5, 1.8) | 0.76 | No effect |
| MSH6 | 16 | 16 | 0.9 (0.5, 1.9) | 0.86 | No effect |
| NBN | 26 | 27 | 1.0 (0.6, 1.8) | 0.87 | No effect |
| PHLPP2 | 32 | 34 | 1.0 (0.6, 1.7) | 0.97 | No effect |
| POLK | 22 | 22 | 1.0 (0.5, 1.8) | 0.99 | No effect |
| RAD51B/REC2/RAD51L1 | 6 | 5 | 0.9 (0.3, 2.8) | 0.80 | No effect |
| RECQL4 | 49 | 55 | 1.1 (0.8, 1.7) | 0.59 | No effect |
| RINT1 | 8 | 8 | 1.0 (0.4, 2.8) | 0.95 | No effect |
| SETX | 25 | 24 | 1.0 (0.6, 1.7) | 0.91 | No effect |
| TELO2 | 17 | 18 | 1.1 (0.5, 2.1) | 0.89 | No effect |
| XRCC2 | 7 | 6 | 0.9 (0.3, 2.7) | 0.84 | No effect |
| APLF | 7 | 11 | 1.5 (0.6, 3.9) | 0.40 | High |
| ATM | 40 | 77 | 1.9 (1.3, 2.9) | 0.001 | High |
| BARD1 | 7 | 9 | 1.3 (0.5, 3.6) | 0.59 | High |
| BRIP1/FANCJ | 16 | 25 | 1.5 (0.8, 2.8) | 0.25 | High |
| CHEK1 | 4 | 6 | 1.2 (0.3, 4.5) | 0.75 | High |
| CHEK2 | 22 | 62 | 3.0 (1.9, 5.0) | 0.00001 | High |
| CHGB | 9 | 11 | 1.2 (0.5, 3.0) | 0.65 | High |
| DCLRE1C | 9 | 14 | 1.6 (0.7, 3.7) | 0.28 | High |
| DGKZ | 33 | 38 | 1.2 (0.7, 1.9) | 0.52 | High |
| ERCC2 | 17 | 27 | 1.6 (0.9, 3.0) | 0.13 | High |
| EYA3 | 6 | 7 | 1.2 (0.4, 3.5) | 0.77 | High |
| FANCM | 23 | 38 | 1.7 (1.0, 2.8) | 0.06 | High |
| FEN1 | 6 | 7 | 1.2 (0.4, 3.6) | 0.74 | High |
| FOXO1 | 6 | 7 | 1.8 (0.5, 6.0) | 0.38 | High |
| FOXO3 | 0 | 8 | - | - | High |
| FOXO4 | 0 | 4 | - | - | High |
| MAST1 | 8 | 17 | 2.2 (0.9, 5.1) | 0.07 | High |
| MCM7 | 10 | 18 | 1.8 (0.8, 4.0) | 0.13 | High |
| MLH1 | 15 | 19 | 1.3 (0.6, 2.5) | 0.52 | High |
| MRE11A | 12 | 14 | 1.2 (0.6, 2.6) | 0.64 | High |
| MSH3 | 25 | 30 | 1.2 (0.7, 2.1) | 0.49 | High |
| NTHL1 | 18 | 22 | 1.2 (0.6, 2.2) | 0.65 | High |
| NUMA1 | 36 | 51 | 1.4 (0.9, 2.2) | 0.12 | High |
| PALB2 | 9 | 30 | 3.5 (1.7, 7.5) | 0.001 | High |
| PIK3R1 | 1 | 4 | 4.3 (0.5, 38.3) | 0.20 | High |
| PMS1 | 6 | 10 | 1.5 (0.6, 4.3) | 0.41 | High |
| PPM1D | 4 | 6 | 1.5 (0.4, 5.4) | 0.53 | High |
| PTEN | 0 | 4 | - | - | High |
| RAD50 | 30 | 37 | 1.2 (0.7, 2.0) | 0.44 | High |
| RAD51C | 7 | 10 | 1.5 (0.6, 4.0) | 0.41 | High |
| RAD9B | 4 | 6 | 1.5 (0.4, 5.2) | 0.55 | High |
| RECQL5 | 20 | 29 | 1.5 (0.9, 2.7) | 0.14 | High |
| REV3L | 31 | 39 | 1.3 (0.8, 2.1) | 0.30 | High |
| RNF168 | 13 | 16 | 1.2 (0.6, 2.6) | 0.59 | High |
| RPA1 | 9 | 14 | 1.5 (0.7, 3.6) | 0.32 | High |
| SLX4/FANCP | 36 | 44 | 1.2 (0.8, 1.9) | 0.38 | High |
| STK11 | 1 | 2 | 2.1 (0.2, 22.9) | 0.55 | High |
| TGFB1 | 5 | 9 | 1.6 (0.5, 4.9) | 0.38 | High |
| TOP3A | 22 | 31 | 1.4 (0.8, 2.5) | 0.23 | High |
| TP53 | 3 | 6 | 2.0 (0.5, 8.0) | 0.34 | High |
| TSC2 | 45 | 56 | 1.3 (0.9, 1.9) | 0.23 | High |
| TTI1 | 26 | 30 | 1.2 (0.7, 2.0) | 0.57 | High |
| UIMC1/RAP80 | 12 | 15 | 1.2 (0.6, 2.7) | 0.58 | High |
| USP8 | 9 | 16 | 1.7 (0.7, 3.8) | 0.23 | High |
| WRN | 47 | 59 | 1.3 (0.9, 1.9) | 0.23 | High |
| XRCC3 | 4 | 7 | 1.8 (0.5, 6.2) | 0.36 | High |
Abbreviations: OR (95%CI) odds ratio (95% confidence interval)
aReference group: non-carrier of a variant in the tested gene
bGroup “Low”: OR <0.9; Group “No Effect”: 0.9≤ OR ≤1.1; Group “High”: OR >1.1