The association of investigated SNPs with risk for malignant mesothelioma
| SNP | Genotype | Controls N (%) | Cases N (%) | OR (95% CI) | P | Cases exposed to asbestos N (%) | OR (95% CI) | P |
|---|---|---|---|---|---|---|---|---|
| MMP2 rs243865 | CC | 90 (55.9) | 155 (65.7) | Ref. | 118 (69.8) | Ref. | ||
| CT | 65 (40.4) | 77 (32.6) | 0.69 (0.45-1.05) | 0.081 | 48 (28.4) | 0.56 (0.35-0.89) | 0.015 | |
| TT | 6 (3.7) | 4 (1.7) | 0.39 (0.11-1.41) | 0.150 | 3 (1.8) | 0.38 (0.09-1.57) | 0.181 | |
| CT+TT | 71 (44.1) | 81 (34.3) | 0.66 (0.44-1.00) | 0.050 | 51 (30.2) | 0.55 (0.35-0.86) | 0.009 | |
| MMP2 rs243849 | CC | 108 (75.0) [17] | 163 (71.5) [8] | Ref. | 116 (71.2) [6] | Ref. | ||
| CT | 33 (22.9) | 57 (25.0) | 1.14 (0.70-1.87) | 0.592 | 42 (25.8) | 1.18 (0.70-2.00) | 0.527 | |
| TT | 3 (2.1) | 8 (3.5) | 1.77 (0.46-6.81) | 0.408 | 5 (3.1) | 1.55 (0.36-6.65) | 0.554 | |
| CT+TT | 36 (25.0) | 65 (28.5) | 1.20 (0.74-1.92) | 0.459 | 47 (28.8) | 1.22 (0.73-2.02) | 0.451 | |
| MMP2 rs7201 | AA | 56 (35.9) [5] | 78 (33.5) [3] | Ref. | 63 (37.5) [1] | Ref. | ||
| AC | 71 (45.5) | 114 (48.9) | 1.15 (0.73-1.81) | 0.539 | 78 (46.4) | 0.98 (0.60-1.58) | 0.923 | |
| CC | 29 (18.6) | 41 (17.6) | 1.02 (0.56-1.82) | 0.960 | 27 (16.1) | 0.83 (0.44-1.56) | 0.560 | |
| AC+CC | 100 (64.1) | 155 (66.5) | 1.11 (0.73-1.70) | 0.622 | 105 (62.5) | 0.93 (0.59-1.47) | 0.765 | |
| MMP9 rs17576 | AA | 64 (40.3) [2] | 100 (42.9) [3] | Ref. | 74 (44.3) [2] | Ref. | ||
| AG | 75 (47.2) | 114 (48.9) | 0.97 (0.63-1.49) | 0.900 | 79 (47.3) | 0.91 (0.57-1.44) | 0.691 | |
| GG | 20 (12.6) | 19 (8.2) | 0.61 (0.30-1.23) | 0.165 | 14 (8.4) | 0.61 (0.28-1.30) | 0.196 | |
| AG+GG | 95 (59.8) | 133 (57.1) | 0.90 (0.59-1.35) | 0.599 | 93 (55.7) | 0.85 (0.55-1.31) | 0.458 | |
| MMP9 rs2250889 | GG | 146 (90.7) | 212 (90.2) [1] | Ref. | 152 (89.9) | Ref. | ||
| GA | 15 (9.3) | 23 (9.8) | 1.06 (0.53-2.09) | 0.876 | 17 (10.1) | 1.09 (0.52-2.26) | 0.820 | |
| MMP9 rs17577 | GG | 113 (70.2) | 169 (72.8) [4] | Ref. | 119 (71.3) [2] | Ref. | ||
| GA | 47 (29.2) | 60 (25.9) | 0.85 (0.54-1.34) | 0.490 | 45 (26.9) | 0.91 (0.56-1.47) | 0.699 | |
| AA | 1 (0.6) | 3 (1.3) | 2.01 (0.21-19.53) | 0.549 | 3 (1.8) | 2.85 (0.29-27.79) | 0.368 | |
| GA+AA | 48 (29.8) | 63 (27.2) | 0.88 (0.56-1.37) | 0.565 | 48 (28.7) | 0.95 (0.59-1.53) | 0.831 | |
| MMP9 rs20544 | CC | 33 (20.6) [1] | 38 (16.3) [3] | Ref. | 29 (17.4) [2] | Ref. | ||
| CT | 74 (46.3) | 121 (51.9) | 1.42 (0.82-2.46) | 0.210 | 82 (49.1) | 1.26 (0.70-2.27) | 0.441 | |
| TT | 53 (33.1) | 74 (31.8) | 1.21 (0.68-2.18) | 0.518 | 56 (33.5) | 1.20 (0.64-2.25) | 0.563 | |
| CT+TT | 127 (79.4) | 195 (83.7) | 1.33 (0.79-2.24) | 0.275 | 138 (82.6) | 1.24 (0.71-2.15) | 0.453 | |
| MMP14 rs1042703 | TT | 90 (57.0) [3] | 147 (63.4) [4] | Ref. | 109 (65.7) [3] | Ref. | ||
| TC | 54 (34.2) | 67 (28.9) | 0.76 (0.49-1.18) | 0.225 | 44 (26.5) | 0.67 (0.41-1.09) | 0.110 | |
| CC | 14 (8.9) | 18 (7.8) | 0.79 (0.37-1.66) | 0.530 | 13 (7.8) | 0.77 (0.34-1.71) | 0.518 | |
| TC+CC | 68 (43.0) | 85 (36.6) | 0.77 (0.51-1.16) | 0.204 | 57 (34.3) | 0.69 (0.44-1.08) | 0.108 | |
| MMP14 rs1042704 | GG | 103 (64.0) | 160 (68.1) [1] | Ref. | 113 (66.9) | Ref. | ||
| GA | 51 (31.7) | 64 (27.2) | 0.81 (0.52-1.26) | 0.346 | 47 (27.8) | 0.84 (0.52-1.35) | 0.475 | |
| AA | 7 (4.3) | 11 (4.7) | 1.01 (0.38-2.69) | 0.982 | 9 (5.3) | 1.17 (0.42-3.26) | 0.761 | |
| GA+AA | 58 (36.0) | 75 (31.9) | 0.83 (0.55-1.27) | 0.395 | 56 (33.1) | 0.88 (0.56-1.39) | 0.581 | |
| MMP14 rs743257 | CC | 40 (26.0) [7] | 59 (25.1) [1] | Ref. | 41 (24.4) [1] | Ref. | ||
| CT | 73 (47.4) | 104 (44.3) | 0.97 (0.59-1.59) | 0.892 | 76 (45.2) | 1.02 (0.59-1.75) | 0.955 | |
| TT | 41 (26.6) | 72 (30.6) | 1.19 (0.68-2.07) | 0.538 | 51 (30.4) | 1.21 (0.67-2.21) | 0.526 | |
| CT+TT | 114 (74.0) | 176 (74.9) | 1.05 (0.66-1.67) | 0.848 | 127 (75.6) | 1.09 (0.66-1.80) | 0.746 |
The association of haplotypes with frequencies above 5% for investigated genes with risk for malignant mesotjelioma in patients with asbestos exposure
| Gene | Haplotype | Estimated frequency | OR (95% CI) | P |
|---|---|---|---|---|
| MMP2 | CCA | 0.377 | Ref. | |
| CCC | 0.272 | 1.14 (0.77 - 1.68) | 0.518 | |
| CTA | 0.144 | 1.14 (0.70 - 1.85) | 0.599 | |
| TCC | 0.144 | 0.77 (0.48 - 1.25) | 0.291 | |
| TCA | 0.056 | 0.59 (0.26 - 1.38) | 0.223 | |
| MMP9 | ACGT | 0.572 | Ref. | |
| GCGC | 0.204 | 0.86 (0.59 - 1.26) | 0.440 | |
| GCAC | 0.137 | 0.81 (0.52 - 1.26) | 0.353 | |
| MMP14 | TGC | 0.338 | Ref. | |
| TGT | 0.267 | 1.39 (0.94 - 2.06) | 0.103 | |
| CGT | 0.125 | 0.85 (0.52 - 1.37) | 0.494 | |
| TAT | 0.110 | 1.23 (0.71 - 2.12) | 0.461 | |
| CGC | 0.080 | 1.33 (0.71 - 2.46) | 0.371 |
Patients’ characteristics (N = 236)
| Characteristic | N (%) | |
|---|---|---|
| Gender | Male | 174 (73.7) |
| Female | 62 (26.3) | |
| Age | Median (25%-75%) | 66 (58-72) |
| Stage | I | 18 (7.6) |
| II | 60 (25.4) | |
| III | 70 (29.7) | |
| IV | 67 (28.4) | |
| Peritoneal | 20 (8.5) | |
| Not determined | 1 (0.4) | |
| Histological type | Epitheloid | 169 (71.6) |
| Biphasic | 27 (11.4) | |
| Sarcomatoid | 26 (11.0) | |
| Not characterized | 14 (5.9) | |
| ECOG performance stats | 0 | 15 (6.4) |
| 1 | 114 (48.3) | |
| 2 | 92 (39.0) | |
| 3 | 15 (6.4) | |
| Metastases | No | 206 (87.3) |
| Yes | 30 (12.7) | |
| Asbestos exposure | Not exposed | 61 (26.5) [6] |
| Exposed | 169 (73.5) | |
| Smoking | No | 123 (57.7) |
| Yes | 106 (46.3) |
Variant allele characteristics, frequencies and agreement with HWE
| Gene | SNP | SNP characteristics | Variant allele frequency | PHWE |
|---|---|---|---|---|
| MMP2 | rs243865 | c.-1306C>T | 0.24 | 0.165 |
| rs243849 | c.999C>T, p.Asp333= | 0.14 | 0.798 | |
| rs7201 | c.∗260A>C | 0.41 | 0.441 | |
| MMP9 | rs17576 | c.836AG, p.Gln279Arg | 0.36 | 0.785 |
| rs2250889 | c.836A>G, p.Gln279Arg | 0.05 | 0.535 | |
| rs17577 | c.2003G>A, p.Arg668Gln | 0.15 | 0.096 | |
| rs20544 | c.∗C>T | 0.44 | 0.445 | |
| MMP14 | rs1042703 | c.22T>C, p.Pro8Ser | 0.26 | 0.164 |
| rs1042704 | c.817G>A, p.Asp273Asn | 0.20 | 0.830 | |
| rs743257 | c.∗3C>T | 0.50 | 0.519 |