A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan
Abstract
:1. Introduction
2. Results
2.1. Demographics of Study Population
2.2. Novel Variants Associated with Oral Cancer in the Taiwanese
2.3. Common Variants Associated with Oral Cancer Validated among Various Populations
3. Discussion
4. Materials and Methods
4.1. Study Population and Data Collection
4.2. Genotyping and Imputation
4.3. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Variables | Cases, N = 1529 | Controls, N = 44,572 |
---|---|---|
Age, mean (SD) | 55 (11.5) | 54 (14.5) |
Sex (N, %) | ||
Male | 1328 (86.9) | 34,616 (77.7) |
Female | 201 (13.1) | 9956 (22.3) |
CHROM | POS | ID | Gene | REF | ALT | OR (95% CI) | p |
---|---|---|---|---|---|---|---|
6 | 31263915 | rs2524113 | TCF19/HLA-C | T | G | 1.32 (1.2–1.46) | 3.40 × 10−8 |
6 | 31264003 | rs2524112 | TCF19/HLA-C | A | G | 1.32 (1.2–1.46) | 3.40 × 10−8 |
6 | 31264212 | rs2853961 | TCF19/HLA-C | G | A | 1.32 (1.2–1.46) | 2.12 × 10−8 |
6 | 31264470 | rs2844624 | TCF19/HLA-C | T | C | 1.32 (1.2–1.46) | 3.40 × 10−8 |
6 | 31264813 | rs2524107 | TCF19/HLA-C | C | T | 1.32 (1.2–1.46) | 3.40 × 10−8 |
6 | 31265454 | rs2246085 | TCF19/HLA-C | A | T | 1.32 (1.2–1.46) | 3.40 × 10−8 |
6 | 31265793 | rs2248885 | HLA-C/CLIC1 | C | T | 1.32 (1.2–1.46) | 3.54 × 10−8 |
6 | 31353774 | rs75456009 | HLA-C/CLIC1 | A | G | 1.32 (1.2–1.44) | 2.77 × 10−9 |
6 | 31353782 | rs74615740 | HLA-C/CLIC1 | C | A | 1.32 (1.21–1.45) | 1.98 × 10−9 |
6 | 31353786 | rs75256987 | HLA-C/CLIC1 | A | C | 1.32 (1.21–1.45) | 1.84 × 10−9 |
6 | 31353800 | rs114322933 | HLA-C/CLIC1 | C | T | 1.32 (1.2–1.45) | 3.01 × 10−9 |
6 | 31353908 | rs1058026 | HLA-B | A | C | 1.34 (1.23–1.47) | 1.87 × 10−10 |
6 | 31949780 | rs4151658 | CFB | C | CAT | 1.37 (1.23–1.53) | 2.41 × 10−8 |
6 | 31963360 | rs401775 | SKIV2L | T | C | 1.34 (1.21–1.49) | 1.25 × 10−8 |
6 | 32077057 | rs9267798 | TNXB | G | C | 0.76 (0.69–0.84) | 1.88 × 10−8 |
Region | SNP | Chrom:Position | Gene | Allele | EAF Cases/Controls | OR | p | OR (95% CI) | p |
---|---|---|---|---|---|---|---|---|---|
Lesseur et al. Nature Genetics, 2016 | (Taiwanese) | (Taiwanese) | |||||||
OC and OPC | |||||||||
4q23 | rs1229984 | 4:100239319 | ADH1B | G/A | 0.03/0.06 | 0.56 | 2.29 × 10−15 | 1.20 (1.06–1.35) | 0.00335 |
6p21.32 | rs3828805 | 6:32636120 | HLA-DQB1 | C/T | 0.75/0.72 | 1.28 | 3.35 × 10−13 | 0.75 (0.58–0.96) | 0.0249 |
10q26.13 | rs201982221 | 10:126157446 | LHPP | Ins/Del | 0.03/0.02 | 1.67 | 1.58 × 10−9 | NA | NA |
11p15.4 | rs1453414 | 11:5829084 | OR52N2–TRIM5 | A/C | 0.23/0.20 | 1.19 | 4.78 × 10−8 | NA | NA |
OC | |||||||||
2p23.3 | rs6547741 | 2:27855924 | GPN1 | G/A | 0.50/0.54 | 0.83 | 3.97 × 10−8 | 1.00 (0.84–1.20) | 0.98 |
4q23 | rs1229984 | 4:100239319 | ADH1B | G/A | 0.03/0.06 | 0.57 | 1.09 × 10−9 | 1.20 (1.06–1.35) | 0.003 |
5p15.33 | rs10462706 | 5:1343794 | CLPTM1L | C/T | 0.12/0.15 | 0.74 | 5.54 × 10−10 | 0.93 (0.83–1.04) | 0.234 |
9p21.3 | rs8181047 | 9:22064465 | CDKN2B-AS1 | G/A | 0.29/0.24 | 1.24 | 3.80 × 10−9 | 1.17 (0.99–1.37) | 0.064 |
9q34.12 | rs928674 | 9:133952024 | LAMC3 | A/G | 0.14/0.12 | 1.33 | 2.09 × 10−8 | 0.75 (0.63–0.90) | 0.002 |
Shete et al. Cancer Research, 2020 | |||||||||
HNSCC | |||||||||
6p22.1 | rs259919 | 6:30025503 | ZNRD1-AS1 | A/G | 0.34/0.31 | 1.15 (1.06–1.25) | 2.96 × 10−9 | 0.94 (0.83–1.07) | 0.353 |
6p21.33 | rs1265081 | 6:31111675 | CCHCR1 | C/A | 0.47/0.5 | 0.85 (0.79–0.92) | 3.75 × 10−10 | 0.95 (0.85–1.07) | 0.414 |
6p21.32 | rs3135001 | 6:32670136 | HLA-DQB1 | T/C | 0.21/0.25 | 0.76 (0.69–0.83) | 1.44 × 10−16 | 0.76 (0.59–0.97) | 0.03 |
OC | |||||||||
5p15.33 | rs10462706 | 5:1343794 | CLPTM1L | T/C | 0.12/0.15 | 0.72 (0.60–0.88) | 7.87 × 10−11 | 0.93 (0.83–1.05) | 0.234 |
6p21.32 | rs1049055 | 6:32634387 | HLA-DQB1 | C/T | 0.23/0.27 | 0.76 (0.66–0.89) | 2.96 × 10−9 | 0.71 (0.55–0.92) | 0.009 |
Ji et al. J Med Genet, 2022 | |||||||||
HNSCC | |||||||||
6p22.1 | rs2517611 | 6:30169327 | TRIM26 | A/G | 0.15/0.11 | 1.32 (1.18–1.47) | 7.45 × 10−7 | 1.22 (0.96–1.55) | 0.096 |
6p21.33 | rs2524182 | 6:31130593 | TRIM39-RPP21, HLA-E | A/T | 0.37/0.31 | 1.27 (1.17–1.37) | 1.76 × 10−9 | 1.04 (0.90–1.21) | 0.562 |
6p21.33 | rs3131018 | 6:31143582 | PSORS1C3-TCF19 | C/A | 0.22/0.30 | 0.77 (0.71–0.83) | 2.17 × 10−10 | 0.84 (0.75–0.94) | 0.004 |
9p21.3 | rs1063192 | 9:22003367 | CDKN2B | A/G | 0.24/0.19 | 1.33 (1.2–1.45) | 4.10 × 10−12 | 1.11 (0.96–1.28) | 0.166 |
McKay et al. Plos Genetics, 2011 | |||||||||
UADT Cancer | |||||||||
4q23 | rs1229984 | 4:99318162 | ADH1B | C/T | EAF: 0.05 | 0.64 (0.59–0.71) | 1.00 × 10−20 | 1.20 (1.06–1.35) | 0.00335 |
4q23 | rs971074 (or rs1573496) | 4:99420704 | ADH7 | G/C | EAF: 0.12 | 0.75 (0.70–0.80) | 9.00 × 10−19 | 1.22 (1.02–1.44) | 0.0264 |
4q23 | rs1789924 (or rs698) | 4:99353129 | ADH1C | T/C | EAF: 0.39 | 1.12 (1.07–1.17) | 3.00 × 10−7 | 1.13 (0.93–1.36) | 0.215 |
12q24 | rs4767364 | 12:112083644 | ALDH2 | G/A | EAF: 0.27 | 1.13 (1.08–1.18) | 2.00 × 10−8 | 0.89 (0.71–1.10) | 0.283 |
4q21 | rs1494961 | 4:83453327 | HEL308 | T/C | EAF: 0.49 | 1.12 (1.08–1.17) | 1.00 × 10−8 | 0.94 (0.83–1.06) | 0.33 |
Region | SNP ID | Chr:Position | Gene | Effect Allele | Other Allele | Europeans | Taiwanese | ||
---|---|---|---|---|---|---|---|---|---|
OR | p | OR | p | ||||||
2p23.3 | rs4665986 | 2:27755168 | A | G | 0.84 | 1.75 × 10−7 | 1.114 | 0.030 | |
2p23.3 | rs4665381 | 2:27757150 | C | A | 0.84 | 1.30 × 10−7 | 1.101 | 0.054 | |
2p23.3 | rs1972669 | 2:27767107 | G | T | 0.84 | 1.50 × 10−7 | 1.101 | 0.054 | |
2p23.3 | rs4493210 | 2:27768072 | T | G | 0.84 | 1.08 × 10−7 | 1.101 | 0.053 | |
2p23.3 | rs1080060 | 2:27768808 | A | T | 0.84 | 1.08 × 10−7 | 1.101 | 0.054 | |
2p23.3 | rs2384626 | 2:27773648 | G | A | 0.84 | 2.93 × 10−7 | 1.101 | 0.054 | |
2p23.3 | rs1820297 | 2:27774924 | G | A | 0.84 | 6.23 × 10−8 | 1.096 | 0.065 | |
2p23.3 | rs6750943 | 2:27777904 | G | T | 0.84 | 9.17 × 10−8 | 1.096 | 0.065 | |
2p23.3 | rs6761095 | 2:27778010 | T | G | 0.84 | 1.78 × 10−7 | 1.096 | 0.065 | |
2p23.3 | rs6706610 | 2:27778091 | A | G | 0.84 | 6.41 × 10−8 | 1.096 | 0.065 | |
2p23.3 | rs6547709 | 2:27783418 | A | G | 0.84 | 8.93 × 10−8 | 1.094 | 0.068 | |
2p23.3 | rs12714204 | 2:27787540 | C | T | 0.84 | 1.66 × 10−7 | 1.094 | 0.068 | |
2p23.3 | rs4260197 | 2:27794150 | G | C | 0.84 | 1.70 × 10−7 | 1.095 | 0.068 | |
2p23.3 | rs10205364 | 2:27794233 | T | C | 0.84 | 1.20 × 10−7 | 1.095 | 0.068 | |
2p23.3 | rs10165098 | 2:27796526 | T | C | 0.84 | 8.30 × 10−8 | 1.095 | 0.068 | |
2p23.3 | rs1919125 | 2:27801403 | C2orf16 | G | C | 0.84 | 1.23 × 10−7 | 1.095 | 0.066 |
2p23.3 | rs1919126 | 2:27801418 | C2orf16 | C | A | 1.19 | 1.28 × 10−7 | 1.095 | 0.066 |
2p23.3 | rs13026621 | 2:27807624 | ZNF512 | A | G | 0.84 | 8.99 × 10−8 | 1.091 | 0.079 |
2p23.3 | rs4665995 | 2:27813827 | ZNF512 | G | T | 0.84 | 9.66 × 10−8 | 1.091 | 0.079 |
2p23.3 | rs4665996 | 2:27814343 | ZNF512 | C | T | 0.84 | 9.96 × 10−8 | 1.091 | 0.079 |
2p23.3 | rs6738089 | 2:27815278 | ZNF512 | G | A | 0.84 | 2.14 × 10−7 | 1.091 | 0.079 |
2p23.3 | rs4665997 | 2:27816989 | ZNF512 | C | T | 0.84 | 1.53 × 10−7 | 1.094 | 0.072 |
2p23.3 | rs7604798 | 2:27824940 | ZNF512 | C | T | 0.84 | 1.81 × 10−7 | 1.089 | 0.087 |
2p23.3 | rs62138969 | 2:27828292 | ZNF512 | A | G | 0.84 | 2.10 × 10−7 | 1.088 | 0.090 |
2p23.3 | rs6547734 | 2:27830990 | ZNF512 | T | G | 0.84 | 1.52 × 10−7 | 1.088 | 0.090 |
2p23.3 | rs6718128 | 2:27833752 | ZNF512 | T | C | 0.84 | 3.19 × 10−7 | 1.088 | 0.091 |
2p23.3 | rs4665999 | 2:27834444 | ZNF512 | C | T | 0.84 | 1.04 × 10−7 | 1.088 | 0.090 |
2p23.3 | rs11127071 | 2:27838058 | ZNF512 | A | C | 0.84 | 1.06 × 10−7 | 1.077 | 0.140 |
2p23.3 | rs6737921 | 2:27839107 | ZNF512 | C | T | 0.84 | 1.08 × 10−7 | 1.076 | 0.141 |
2p23.3 | rs6756238 | 2:27841305 | ZNF512 | A | G | 0.84 | 1.11 × 10−7 | 1.074 | 0.153 |
2p23.3 | rs1528404 | 2:27846603 | C | T | 0.84 | 1.56 × 10−7 | 1.062 | 0.312 | |
2p23.3 | rs1528403 | 2:27846645 | G | C | 0.85 | 3.86 × 10−7 | 1.059 | 0.336 | |
2p23.3 | rs2384654 | 2:27847364 | T | C | 0.84 | 1.78 × 10−7 | 1.059 | 0.335 | |
2p23.3 | rs4666005 | 2:27855239 | GPN1 | G | A | 0.84 | 2.14 × 10−7 | 1.072 | 0.237 |
2p23.3 | rs2384659 | 2:27856793 | GPN1 | A | G | 0.84 | 6.71 × 10−8 | 1.072 | 0.236 |
2p23.3 | rs4666009 | 2:27857992 | GPN1 | A | T | 0.84 | 1.75 × 10−7 | 1.073 | 0.235 |
2p23.3 | rs56001553 | 2:27859926 | GPN1 | T | C | 1.19 | 2.53 × 10−7 | 1.068 | 0.265 |
5p15.33 | rs7726159 | 5:1282319 | TERT | A | C | 1.19 | 2.18 × 10−7 | 1.161 | 6.40 × 10−5 |
5p15.33 | rs60622800 | 5:1309904 | MIR4457 | A | G | 0.84 | 6.56 × 10−8 | 1.141 | 0.004 |
5p15.33 | rs6554758 | 5:1310152 | MIR4457 | A | G | 0.84 | 6.24 × 10−8 | 1.141 | 0.004 |
5p15.33 | rs380286 | 5:1320247 | CLPTM1L | A | G | 1.18 | 3.16 × 10−7 | 1.172 | 0.001 |
5p15.33 | rs13178866 | 5:1323212 | CLPTM1L | A | G | 1.19 | 8.00 × 10−8 | 1.149 | 0.002 |
5p15.33 | rs466502 | 5:1325767 | CLPTM1L | G | A | 1.19 | 1.31 × 10−7 | 1.152 | 0.002 |
5p15.33 | rs465498 | 5:1325803 | CLPTM1L | G | A | 1.19 | 5.48 × 10−8 | 1.156 | 0.001 |
5p15.33 | rs452384 | 5:1330840 | CLPTM1L | G | A | 1.19 | 5.74 × 10−8 | 1.156 | 0.001 |
5p15.33 | rs370348 | 5:1331219 | CLPTM1L | G | A | 1.19 | 5.83 × 10−8 | 1.149 | 0.002 |
9p21.3 | rs944800 | 9:22050898 | CDKN2B-AS1 | A | G | 1.21 | 7.42 × 10−8 | 1.059 | 0.342 |
9p21.3 | rs2383205 | 9:22060935 | CDKN2B-AS1 | A | G | 1.20 | 2.55 × 10−7 | 1.036 | 0.542 |
9p21.3 | rs1537378 | 9:22061614 | CDKN2B-AS1 | A | G | 1.20 | 1.68 × 10−7 | 1.033 | 0.575 |
9p21.3 | rs8181050 | 9:22064391 | CDKN2B-AS1 | G | A | 1.20 | 1.74 × 10−7 | 1.028 | 0.634 |
9q34.12 | rs3765566 | 9:133942766 | LAMC3 | G | A | 1.31 | 2.28 × 10−7 | 0.931 | 0.307 |
9q34.12 | rs7875478 | 9:133947180 | LAMC3 | T | A | 1.32 | 1.23 × 10−7 | 0.932 | 0.312 |
9q34.12 | rs7858204 | 9:133947345 | LAMC3 | A | G | 1.32 | 1.20 × 10−7 | 0.930 | 0.295 |
9q34.12 | rs10901348 | 9:133956465 | LAMC3 | A | G | 1.31 | 7.12 × 10−8 | 1.062 | 0.270 |
9q34.12 | rs72768533 | 9:133959518 | LAMC3 | G | C | 1.31 | 6.82 × 10−8 | 0.981 | 0.783 |
9q34.12 | rs72768534 | 9:133959740 | LAMC3 | C | G | 1.31 | 6.77 × 10−8 | 0.981 | 0.785 |
9q34.12 | rs77452476 | 9:133962573 | LAMC3 | G | T | 1.29 | 5.97 × 10−8 | 0.986 | 0.748 |
9q34.12 | rs11791030 | 9:133971049 | LOC105376298 | G | T | 1.31 | 1.68 × 10−7 | 0.985 | 0.834 |
15q21.2 | rs12910284 | 15:49785916 | LOC105370811 | G | A | 1.19 | 4.28 × 10−7 | 1.029 | 0.438 |
15q21.2 | rs10851478 | 15:49829019 | LOC105370811 | G | A | 1.19 | 3.47 × 10−7 | 1.030 | 0.419 |
6p21.33 | rs3132451 | 6:31582025 | AIF1 | C | G | 1.25 | 4.59 × 10−7 | 0.866 | 0.029 |
6p21.32 | rs9271378 | 6:32587300 | G | A | 1.19 | 2.05 × 10−7 | 1.017 | 0.694 | |
6p21.32 | rs17612852 | 6:32620572 | HLA-DQA1 | A | G | 1.23 | 4.21 × 10−7 | 0.929 | 0.078 |
6p21.32 | rs4713570 | 6:32626040 | T | C | 1.25 | 1.03 × 10−7 | 0.831 | 0.004 | |
6p21.32 | rs1049213 | 6:32627773 | HLA-DQB1 | G | A | 1.24 | 4.65 × 10−7 | 0.910 | 0.018 |
6p21.32 | rs3828805 | 6:32636120 | HLA-DQB1 | C | T | 1.23 | 2.83 × 10−7 | 0.910 | 0.217 |
6p21.32 | rs3135002 | 6:32668439 | C | A | 1.27 | 1.71 × 10−7 | 0.887 | 0.132 |
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Bau, D.-T.; Liu, T.-Y.; Tsai, C.-W.; Chang, W.-S.; Gu, J.; Yang, J.-S.; Shih, L.-C.; Tsai, F.-J. A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan. Int. J. Mol. Sci. 2023, 24, 2789. https://doi.org/10.3390/ijms24032789
Bau D-T, Liu T-Y, Tsai C-W, Chang W-S, Gu J, Yang J-S, Shih L-C, Tsai F-J. A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan. International Journal of Molecular Sciences. 2023; 24(3):2789. https://doi.org/10.3390/ijms24032789
Chicago/Turabian StyleBau, Da-Tian, Ting-Yuan Liu, Chia-Wen Tsai, Wen-Shin Chang, Jian Gu, Jai-Sing Yang, Liang-Chun Shih, and Fuu-Jen Tsai. 2023. "A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan" International Journal of Molecular Sciences 24, no. 3: 2789. https://doi.org/10.3390/ijms24032789
APA StyleBau, D.-T., Liu, T.-Y., Tsai, C.-W., Chang, W.-S., Gu, J., Yang, J.-S., Shih, L.-C., & Tsai, F.-J. (2023). A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan. International Journal of Molecular Sciences, 24(3), 2789. https://doi.org/10.3390/ijms24032789