Table 1.
Risk of contralateral breast cancer associated with radiation dose by single-nucleotide polymorphism genotype
| Homozygous; reference allele | Heterozygous | Homozygous; risk allele | P value e | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SNPa/gene region | RT dose b | Casesc (CBC) | Controls (UBC) | RRd (95% CI) | Casesc (CBC) | Controls (UBC) | RRd (95% CI) | Casesc (CBC) | Controls (UBC) | RRd (95% CI) | |
| rs2981582/FGFR2 | 0 | 93 | 75 | 1.0 | 139 | 119 | 1.0 | 66 | 39 | 1.0 | |
| 0 < 1.0 | 40 | 172 | 0.9 (0.6-1.5) | 88 | 253 | 1.3 (0.9-1.9) | 40 | 108 | 1.0 (0.6-1.8) | 0.39 | |
| 1.0+ | 41 | 131 | 1.2 (0.8-2.0) | 74 | 212 | 1.4 (1.0-2.1) | 25 | 85 | 0.8 (0.4-1.4) | ||
| rs1219648/FGFR2 | 0 | 80 | 74 | 1.0 | 147 | 117 | 1.0 | 71 | 42 | 1.0 | |
| 0 < 1.0 | 40 | 165 | 1.1 (0.7-1.8) | 85 | 256 | 1.2 (0.8-1.7) | 44 | 112 | 1.1 (0.7-1.9) | 0.37 | |
| 1.0+ | 34 | 124 | 1.3 (0.8-2.2) | 79 | 216 | 1.4 (1.0-2.0) | 27 | 89 | 0.8 (0.5-1.5) | ||
| rs3803662/TOX3 | 0 | 116 | 115 | 1.0 | 141 | 97 | 1.0 | 40 | 21 | 1.0 | |
| 0 < 1.0 | 85 | 238 | 1.6 (1.1-2.3) | 66 | 242 | 0.9 (0.6-1.3) | 17 | 52 | 0.9 (0.4-2.0) | 0.07 | |
| 1.0+ | 63 | 199 | 1.5 (1.0-2.3) | 57 | 175 | 1.1 (0.7-1.6) | 19 | 54 | 0.8 (0.4-1.8) | ||
| rs13281615/8q24 | 0 | 89 | 67 | 1.0 | 141 | 128 | 1.0 | 70 | 39 | 1.0 | |
| 0 < 1.0 | 45 | 159 | 1.0 (0.6-1.6) | 80 | 269 | 1.2 (0.9-1.7) | 42 | 103 | 1.1 (0.6-1.9) | 0.99 | |
| 1.0+ | 41 | 132 | 1.2 (0.7-2.0) | 71 | 226 | 1.3 (0.9-1.8) | 28 | 71 | 1.2 (0.6-2.1) | ||
| rs13387042/2q35 | 0 | 66 | 55 | 1.0 | 147 | 114 | 1.0 | 86 | 62 | 1.0 | |
| 0 < 1.0 | 31 | 118 | 1.1 (0.6-1.8) | 75 | 259 | 1.1 (0.8-1.5) | 61 | 155 | 1.3 (0.8-2.1) | 0.45 | |
| 1.0+ | 34 | 107 | 1.1 (0.6-1.9) | 59 | 202 | 1.1 (0.8-1.7) | 46 | 120 | 1.4 (0.9-2.2) | ||
| rs11235127 | 0 | 205 | 162 | 1.0 | 81 | 66 | 1.0 | 13 | 5 | 1.0 | |
| /TMEM135 | 0 < 1.0 | 109 | 374 | 1.1 (0.8-1.5) | 50 | 144 | 1.3 (0.8-2.1) | 9 | 15 | 0.7 (0.2-3.1) | 0.78 |
| 1.0+ | 91 | 306 | 1.2 (0.9-1.6) | 39 | 108 | 1.3 (0.8-2.3) | 9 | 13 | 1.1 (0.3-4.3) | ||
| rs7313833/PTHLH | 0 | 124 | 103 | 1.0 | 134 | 97 | 1.0 | 41 | 31 | 1.0 | |
| 0 < 1.0 | 57 | 232 | 1.0 (0.6-1.4) | 83 | 257 | 1.1 (0.8-1.6) | 27 | 40 | 2.3 (1.1-4.9) | 0.42 | |
| 1.0+ | 56 | 194 | 1.1 (0.8-1.7) | 62 | 185 | 1.2 (0.8-1.8) | 21 | 45 | 1.7 (0.8-3.6) | ||
| rs7696175/4p14 | 0 | 114 | 72 | 1.0 | 127 | 110 | 1.0 | 58 | 51 | 1.0 | |
| 0 < 1.0 | 65 | 185 | 1.0 (0.7-1.6) | 77 | 242 | 1.4 (1.0-2.0) | 26 | 103 | 0.9 (0.5-1.7) | 0.97 | |
| 1.0+ | 49 | 141 | 1.1 (0.7-1.7) | 69 | 208 | 1.5 (1.0-2.1) | 21 | 79 | 1.0 (0.5-1.8) | ||
| rs2107425/H19 | 0 | 132 | 96 | 1.0 | 137 | 110 | 1.0 | 29 | 27 | 1.0 | |
| 0 < 1.0 | 86 | 265 | 1.1 (0.8-1.6) | 64 | 211 | 1.1 (0.7-1.6) | 16 | 56 | 1.4 (0.6-3.1) | 0.14 | |
| 1.0+ | 60 | 217 | 0.9 (0.6-1.4) | 66 | 167 | 1.6 (1.1-2.3) | 14 | 43 | 1.5 (0.6-3.5) | ||
aSingle-nucleotide polymorphisms (SNPs) that had a main effect on contralateral breast cancer (CBC) risk with a P value of less than 0.1 were selected for radiation therapy (RT) dose interaction analysis (rs2107425 did not meet this criterion but is included because of a report [36] that occupational radiation dose affects rs2107425-associated breast cancer risk). bRadiation dose to the contralateral breast (mean = 1.1 Gy) in the quadrant where the second primary tumor occurred. cTotal number of case subjects and matched control subjects for whom there were location-specific dose estimates ranged from 604 to 607 cases and 1,184 to 1,195 controls, depending on the number of genotyped subjects per SNP. dRate ratio (RR) adjusted for age at diagnosis of first primary tumor and the weighting factor that accounts for the counter-matched design. eOne degree of freedom trend test for modification of radiation dose effect by SNP genotype. CI, confidence interval; UBC, unilateral breast cancer.