Table 1.
Association analysis between polymorphisms of DNA methyltransferase genes and risk of grade ≥ 2 radiation-induced fibrosis (LENT-SOMA scale) in breast cancer patients
| SNP | Grade 0-1, n (%) | ≥ Grade 2, n (%) | Unadjusted analysis |
Adjusted analysis |
||
|---|---|---|---|---|---|---|
| HR (95% CI) | p-value | HR (95% CI)a) | p-value | |||
| DNMT1 rs2228611 A>G | ||||||
| Codominant model | ||||||
| AA | 63 (26.8) | 20 (39.2) | 1 (reference) | 1 (reference) | ||
| AG | 108 (46.0) | 26 (51.0) | 0.75 (0.42-1.34) | 0.34 | 0.83 (0.45-1.52) | 0.54 |
| GG | 64 (27.2) | 5 (9.8) | 0.26 (0.10-0.70) | 0.007 | 0.26 (0.10-0.71) | 0.009 |
| Dominant model | ||||||
| AA | 63 (26.8) | 20 (39.2) | 1 (reference) | 1 (reference) | ||
| AG+GG | 172 (73.2) | 31 (60.8) | 0.58 (0.33-1.01) | 0.056 | 0.61 (0.34-1.10) | 0.1 |
| Recessive model | ||||||
| AA+AG | 171 (72.8) | 46 (90.2) | 1 (reference) | 1 (reference) | ||
| GG | 64 (27.2) | 5 (9.8) | 0.31 (0.12-0.78) | 0.013 | 0.29 (0.12-0.75) | 0.011 |
| DNMT3A rs7581217 C>T | ||||||
| Codominant model | ||||||
| CC | 98 (41.7) | 23 (45.1) | 1 (reference) | 1 (reference) | ||
| CT | 106 (45.1) | 24 (47.1) | 0.95 (0.54-1.68) | 0.86 | 0.89 (0.49-1.61) | 0.7 |
| TT | 31 (13.2) | 4 (7.8) | 0.60 (0.21-1.71) | 0.34 | 0.65 (0.22-1.92) | 0.44 |
| Dominant model | ||||||
| CC | 98 (41.7) | 23 (45.1) | 1 (reference) | 1 (reference) | ||
| CT+TT | 137 (58.3) | 28 (54.9) | 0.87 (0.50-1.51) | 0.63 | 0.85 (0.48-1.50) | 0.57 |
| Recessive model | ||||||
| CC+CT | 204 (86.8) | 47 (92.2) | 1 (reference) | 1 (reference) | ||
| TT | 31 (13.2) | 4 (7.8) | 0.61 (0.22–1.69) | 0.34 | 0.70 (0.25–1.95) | 0.49 |
| DNMT3A rs1550117 G>A | ||||||
| Codominant model | ||||||
| GG | 191 (81.3) | 46 (90.2) | 1 (reference) | 1 (reference) | ||
| GA | 41 (17.4) | 5 (9.8) | 0.60 (0.24-1.51) | 0.28 | 0.58 (0.22-1.54) | 0.28 |
| AA | 3 (1.3) | 0 | NC | NC | NC | NC |
| Dominant model | ||||||
| GG | 191 (81.3) | 46 (90.2) | 1 (reference) | 1 (reference) | ||
| GA+AA | 44 (18.7) | 5 (9.8) | 0.55 (0.22-1.38) | 0.21 | 0.57 (0.22-1.49) | 0.25 |
| Recessive model | ||||||
| GG+GA | 232 (98.7) | 51 (100) | 1 (reference) | 1 (reference) | ||
| AA | 3 (1.3) | 0 | NC | NC | NC | NC |
| DNMT3B rs2424908 C>T | ||||||
| Codominant model | ||||||
| CC | 176 (74.9) | 36 (70.6) | 1 (reference) | 1 (reference) | ||
| CT | 52 (22.1) | 14 (27.5) | 1.16 (0.63-2.15) | 0.63 | 1.17 (0.61-2.22) | 0.64 |
| TT | 7 (3.0) | 1 (2.0) | 0.95 (0.13-6.88) | 0.96 | 0.83 (0.11-6.20) | 0.86 |
| Dominant model | ||||||
| CC | 176 (74.9) | 36 (70.6) | 1 (reference) | 1 (reference) | ||
| CT+TT | 59 (25.1) | 15 (29.4) | 1.15 (0.63-2.09) | 0.66 | 1.13 (0.61-2.11) | 0.69 |
| Recessive model | ||||||
| CC+CT | 228 (97.0) | 50 (98.0) | 1 (reference) | 1 (reference) | ||
| TT | 7 (3.0) | 1 (2.0) | 0.91 (0.13-6.56) | 0.93 | 0.81 (0.11-5.98) | 0.83 |
LENT-SOMA, Late Effects of Normal Tissue–Subjective Objective Management Analytical; SNP, single nucleotide polymorphism; HR, hazard ratio; 95% CI, 95% confidence interval; NC, not calculated.
a)
Adjusted by mitochondrial haplogroup (H vs. non-H), body mass index, breast diameter, adjuvant treatment, dose per fraction, radiation quality, acute skin toxicity, and postsurgical complications.