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Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Danijela Strbac
Danijela Strbac
, 
Katja Goricar
Katja Goricar
, 
Vita Dolzan
Vita Dolzan
 and 
Viljem Kovac
Viljem Kovac
   | Feb 07, 2018
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Article Category: Research Article
Published Online: Feb 07, 2018
Page range: 160 - 166
Received: Dec 10, 2017
Accepted: Dec 17, 2017
DOI: https://doi.org/10.2478/raon-2018-0005
© 2018 Danijela Strbac, Katja Goricar, Vita Dolzan, Viljem Kovac, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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
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