Effect of WW Domain-Containing Oxidoreductase Gene Polymorphism on Clinicopathological Characteristics of Patients with EGFR Mutant Lung Adenocarcinoma in Taiwan
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Specimens
2.2. EGFR Gene Sequencing
2.3. Genotyping of WWOX Polymorphisms
2.4. Statistical Analysis
3. Results
3.1. Characteristics of Study Participants
3.2. Distribution Frequency of WWOX Genotypes in Lung Adenocarcinoma Patients
3.3. Correlation between WWOX SNPs and the Tumor Classification in Lung Adenocarcinoma Patients
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Wild Type (N = 127) n (%) | EGFR Mutation (N = 189) n (%) | p Value |
---|---|---|---|
Age | |||
Mean + SD | 65.23 + 13.29 | 66.32 + 13.44 | p = 0.479 |
Gender | |||
Male | 79 (62.6%) | 69 (36.5%) | p < 0.001 |
Female | 48 (37.8%) | 120 (63.5%) | |
Cigarette smoking status | |||
Never-smoker | 55 (43.3%) | 145 (76.7%) | p < 0.001 |
Ever-smoker | 72 (56.7%) | 44 (23.3%) | |
stage | |||
I + II | 29 (22.8%) | 50 (26.5%) | p = 0.466 |
III + IV | 98 (77.2%) | 139 (73.5%) | |
Tumor T status | |||
T1 + T2 | 65 (51.2%) | 115 (60.8%) | p = 0.089 |
T3 + T4 | 62 (48.8%) | 74 (39.2%) | |
Lymph node status | |||
Negative | 32 (25.2%) | 60 (31.7%) | p = 0.209 |
Positive | 95 (74.8%) | 129 (68.3%) | |
Distant Metastasis | |||
Negative | 59 (46.5%) | 85 (45.0%) | p = 0.795 |
Positive | 68 (53.5%) | 104 (55.0%) |
Variable | Wild Type (N = 127) (%) | Mutation Type (N = 189) (%) | OR (95% CI) | AOR (95% CI) |
---|---|---|---|---|
rs11545028 | ||||
CC | 72 (56.7%) | 96 (50.8%) | 1.00 | 1.00 |
CT | 44 (34.6%) | 83 (43.9%) | 1.415 (0.879–2.278) | 1.610 (0.860–3.013) |
TT | 11 (8.7%) | 10 (5.3%) | 0.682 (0.275–1.693) | 0.757 (0.222–2.578) |
CT + TT | 55 (43.3%) | 93 (49.2%) | 1.268 (0.807–1.993) | 1.446 (0.796–2.626) |
rs12918952 | ||||
GG | 117 (92.1%) | 172 (91.0%) | 1.00 | 1.00 |
GA | 10 (7.9%) | 14 (7.4%) | 0.952 (0.409–2.217) | 1.019 (0.352–2.945) |
AA | 0 (0%) | 3 (1.6%) | --- | --- |
GA + AA | 10 (7.9%) | 17 (9.0%) | 1.156 (0.512–2.614) | 1.229 (0.443–3.410) |
rs3764340 | ||||
CC | 107 (84.3%) | 157 (83.1%) | 1.00 | 1.00 |
CG | 18 (14.2%) | 30 (15.9%) | 1.136 (0.603–2.141) | 1.315 (0.585–2.955) |
GG | 2 (1.5%) | 2 (1.0%) | 0.682 (0.095–4.913) | 1.195 (0.099–14.461) |
CG + GG | 20 (15.7%) | 32 (16.9%) | 0.966 (0.763–1.225) | 1.304 (0.599–2.836) |
rs73569323 | ||||
CC | 105 (82.7%) | 166 (87.8%) | 1.00 | 1.00 |
CT | 22 (17.3%) | 23 (12.2%) | 0.661 (0.351–1.246) | 0.622 (0.258–1.500) |
TT | 0 (0%) | 0 (0%) | ---- | ---- |
CT + TT | 22 (17.3%) | 23 (12.2%) | 0.661 (0.351–1.246) | 0.622 (0.258–1.500) |
rs383362 | ||||
GG | 97 (76.4%) | 155 (82.0%) | 1.00 | 1.00 |
GT | 26 (20.5%) | 32 (16.9%) | 0.770 (0.433–1.371) | 0.626 (0.292–1.341) |
TT | 4 (3.1%) | 2 (1.1%) | 0.313 (0.056–1.741) | 0.207 (0.023–1.884) |
GT + TT | 30 (23.6%) | 34 (18.0%) | 0.709 (0.408–1.233) | 0.563 (0.271–1.170) |
Variable | Wild Type | L858R | Exon 19 in-Frame Deletion | ||
---|---|---|---|---|---|
(N = 127) (%) | (N = 89) (%) | OR (95% CI) | (N = 91) (%) | OR (95% CI) | |
rs11545028 | |||||
CC | 72 (56.7%) | 42 (47.2%) | 1.00 | 51 (56.0%) | 1.00 |
CT | 44 (34.6%) | 44 (49.4%) | 1.714 (0.874–3.017) | 33 (36.3%) | 1.059 (0.595–1.885) |
TT | 11 (8.7%) | 3 (3.4%) | 0.263 (0.468–1.772) | 7 (7.7%) | 0.898 (0.326–2.475) |
CT + TT | 55 (43.3%) | 47 (52.8%) | 1.465 (0.850–2.525) | 40 (44.0%) | 1.027 (0.597–1.767) |
rs12918952 | |||||
GG | 117 (92.1%) | 80 (89.9%) | 1.00 | 83 (91.2%) | 1.00 |
GA | 10 (7.9%) | 8 (9.0%) | 1.170 (0.443–3.093) | 6 (6.6%) | 0.846 (0.296–2.418) |
AA | 0 (0%) | 1 (1.1%) | --- | 2 (2.2%) | --- |
GA + AA | 10 (7.9%) | 9 (10.1%) | 1.316 (0.512–3.384) | 8 (8.8%) | 1.128 (0.427–2.979) |
rs3764340 | |||||
CC | 107 (84.3%) | 71 (79.8%) | 1.00 | 78 (85.7%) | 1.00 |
CG | 18 (14.2%) | 16 (18.0%) | 1.340 (0.641–2.800) | 13 (14.3%) | 0.991 (0.458–2.141) |
GG | 2 (1.5%) | 2 (2.2%) | 1.507 (0.207–10.946) | 0 (0%) | --- |
CG + GG | 20 (15.7%) | 18 (20.2%) | 1.356 (0.671–2.742) | 13 (14.3%) | 0.892 (0.418–1.901) |
rs73569323 | |||||
CC | 105 (82.7%) | 79 (88.8%) | 1.00 | 78 (85.7%) | 1.00 |
CT | 22 (17.3%) | 10 (11.2%) | 0.604 (0.271–1.348) | 13 (14.3%) | 0.795 (0.377–1.677) |
TT | 0 (0%) | 0 (0%) | ---- | 0 (0%) | ---- |
CT + TT | 22 (17.3%) | 10 (11.2%) | 0.604 (0.271–1.348) | 13 (14.3%) | 0.795 (0.377–1.677) |
rs383362 | |||||
GG | 97 (76.4%) | 74 (83.1%) | 1.00 | 72 (79.1%) | 1.00 |
GT | 26 (20.5%) | 13 (14.6%) | 0.655 (0.315–1.362) | 19 (20.9%) | 0.985 (0.506–1.915) |
TT | 4 (3.1%) | 2 (2.3%) | 0.655 (0.117–3.675) | 0 (0%) | --- |
GT + TT | 30 (23.6%) | 15 (16.9%) | 0.655 (0.329–1.306) | 19 (20.9%) | 0.853 (0.445–1.635) |
Variable | EGFR Mutation (N = 189) | L858R (N = 89) | Exon 19 in-Frame Deletion (N = 91) | ||||||
---|---|---|---|---|---|---|---|---|---|
CC (N = 157) | CG + GG (N = 32) | p Value | CC (N = 71) | CG + GG (N = 18) | p Value | CC (N = 78) | CG + GG (N = 13) | p Value | |
Stage | |||||||||
I + II | 43 (27.4%) | 7 (21.9%) | p = 0.519 | 22 (31.0%) | 4 (22.2%) | p = 0.465 | 20 (25.6%) | 3 (23.1%) | p = 0.844 |
III + IV | 114 (72.6%) | 25 (78.1%) | 49 (69.0%) | 14 (77.8%) | 58 (74.4%) | 10 (76.9%) | |||
Tumor T status | |||||||||
T1 + T2 | 99 (63.1%) | 16 (50.0%) | p = 0.168 | 53 (74.6%) | 8 (44.4%) | p = 0.014 *,b | 42 (53.8%) | 8 (61.5%) | p = 0.606 |
T3 + T4 | 58 (36.9%) | 16 (50.0%) | 18 (25.4%) | 10 (55.6%) | 36 (46.2%) | 5 (38.5%) | |||
Lymph node status | |||||||||
Negative | 56 (35.7%) | 4 (12.5%) | p = 0.010 *,a | 28 (39.4%) | 2 (11.1%) | p = 0.023 *,c | 27 (34.6%) | 2 (15.4%) | p = 0.168 |
Positive | 101 (64.3%) | 28 (87.5%) | 43 (60.6%) | 16 (88.9%) | 51 (65.4%) | 11 (84.6%) | |||
Distant Metastasis | |||||||||
Negative | 71 (45.2%) | 14 (43.8%) | p = 0.879 | 39 (45.2%) | 8 (43.8%) | p = 0.426 | 29 (37.2%) | 6 (46.2%) | p = 0.538 |
Positive | 86 (54.8%) | 18 (56.2%) | 32 (54.8%) | 10 (56.2%) | 49 (62.8%) | 7 (53.8%) |
Variable | EGFR Mutation (N = 189) | L858R (N = 89) | Exon 19 in-Frame Deletion (N = 91) | ||||||
---|---|---|---|---|---|---|---|---|---|
CC (N = 166) | CT + TT (N = 23) | p Value | CC (N = 79) | CT + TT (N = 10) | p Value | CC (N = 78) | CT + TT (N = 13) | p Value | |
Stage | |||||||||
I + II | 46 (27.7%) | 4 (17.4%) | p = 0.293 | 23 (29.1%) | 3 (30.0%) | p = 0.954 | 2 (28.2%) | 1 (7.7%) | p = 0.115 |
III + IV | 120 (72.3%) | 19 (82.6%) | 56 (70.9%) | 7 (70.0%) | 56 (71.8%) | 12 (92.3%) | |||
Tumor T status | |||||||||
T1 + T2 | 105 (63.3%) | 10 (43.5%) | p = 0.069 | 57 (72.2%) | 4 (40.0%) | p = 0.039 *,a | 44 (56.4%) | 6 (46.2%) | p = 0.491 |
T3 + T4 | 61 (36.7%) | 13 (56.5%) | 22 (27.8%) | 6 (60.0%) | 34 (43.6%) | 7 (53.8%) | |||
Lymph node status | |||||||||
Negative | 54 (32.5%) | 6 (26.1%) | p = 0.534 | 27 (34.2%) | 3 (30.0%) | p = 0.792 | 26 (33.3%) | 3 (23.1%) | p = 0.462 |
Positive | 112 (67.5%) | 17 (73.9%) | 52 (65.8%) | 7 (70.0%) | 52 (66.7%) | 10 (76.9%) | |||
Distant Metastasis | |||||||||
Negative | 78 (47.0%) | 7 (30.4%) | p = 0.135 | 43 (54.4%) | 4 (40.0%) | p = 0.389 | 32 (41.0%) | 3 (23.1%) | p = 0.218 |
Positive | 7 (53.0%) | 16 (69.6%) | 36 (45.6%) | 6 (60.0%) | 46 (59.0%) | 10 (76.9%) |
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Li, J.-P.; Chang, J.T.; Ju, P.-C.; Hsieh, M.-H.; Chao, Y.-H.; Tsao, T.C.-Y.; Hsieh, M.-J.; Yang, S.-F. Effect of WW Domain-Containing Oxidoreductase Gene Polymorphism on Clinicopathological Characteristics of Patients with EGFR Mutant Lung Adenocarcinoma in Taiwan. Int. J. Environ. Res. Public Health 2021, 18, 13136. https://doi.org/10.3390/ijerph182413136
Li J-P, Chang JT, Ju P-C, Hsieh M-H, Chao Y-H, Tsao TC-Y, Hsieh M-J, Yang S-F. Effect of WW Domain-Containing Oxidoreductase Gene Polymorphism on Clinicopathological Characteristics of Patients with EGFR Mutant Lung Adenocarcinoma in Taiwan. International Journal of Environmental Research and Public Health. 2021; 18(24):13136. https://doi.org/10.3390/ijerph182413136
Chicago/Turabian StyleLi, Ju-Pi, Jinghua Tsai Chang, Po-Chung Ju, Ming-Hong Hsieh, Yu-Hua Chao, Thomas Chang-Yao Tsao, Ming-Ju Hsieh, and Shun-Fa Yang. 2021. "Effect of WW Domain-Containing Oxidoreductase Gene Polymorphism on Clinicopathological Characteristics of Patients with EGFR Mutant Lung Adenocarcinoma in Taiwan" International Journal of Environmental Research and Public Health 18, no. 24: 13136. https://doi.org/10.3390/ijerph182413136