Table 2.
Association results of leading SNPs in overall HNSCC, OPC, and non-OPC in MVP Discovery and MDAC Validation Cohort.
| Discovery | Validation | Meta-analysis | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Genic locationa | MAF | Logistic regressionb | Logistic regressionb | Logistic regressionb | |||||||
| Chr. loci* | Gene | rs ID# | Tissue-specific eQTL | Case | Control | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value |
| Overall HNSCC in NHWs | |||||||||||
| 5q35.1 | FGF18 | rs67585403 | intergenic | 0.23 | 0.24 | 0.90 (0.86–0.94) | 4.6 × 10−5 | 0.99 (0.89–1.10) | 0.7658 | 0.95 (0.84–1.05) | 0.0098 |
| 6p21.32 *h*c | HLA-DRB5 | rs111834747 | promoter | 0.37 | 0.29 | 1.35 (1.22–1.50) | 5.5 × 10−7 | 1.19 (1.11–1.27) | 2.5 × 10−7 | 1.28 (1.12–1.47) | 2.6 × 10−9 |
| HLA-DRB1 | rs28724008 | intron | 0.37 | 0.30 | 1.23 (1.13–1.33) | 1.3 × 10−6 | 1.15 (1.08–1.23) | 5.2 × 10−5 | 1.19 (1.06–1.32) | 7.4 × 10−8 | |
| HLA-DQB1 | rs6928482 | downstream, eQTL−l-s | 0.32 | 0.29 | 1.24 (1.13–1.35) | 2.2 × 10−6 | 1.24 (1.13–1.36) | 4.5 × 10−6 | 1.24 (1.10–1.39) | 2.2 × 10−8 | |
| 9q31.1 | SMC2 | rs3818625 | promoter, eQTL−s | 0.43 | 0.44 | 0.92 (0.88–0.95) | 4.1 × 10−5 | 0.91 (0.82–1.04) | 0.1619 | 0.90 (0.82–1.02) | 4.1 × 10−4 |
| 16q24.3 | FANCA | rs12931267 | intron, eQTL−l-s | 0.08 | 0.07 | 1.17 (1.09–1.30) | 2.3 × 10−5 | 0.99 (0.83–1.11) | 0.7512 | 1.14 (0.98–1.28) | 0.0099 |
| 19p13.2 *c | ICAM5 | rs11575074 | downstream | 0.06 | 0.05 | 1.21 (1.10–1.31) | 8.4 × 10−6 | 1.06 (0.95–1.18) | 0.3757 | 1.16 (1.01–1.29) | 0.0045 |
| Overall HNSCC in African-Americans | |||||||||||
| 6p21.32 *h*c | HLA-G | rs1130356 | p.H117H, eQTL−l-s | 0.23 | 0.28 | 0.70 (0.57–0.86) | 4.8 × 10−4 | — | — | — | — |
| 9q21.33 | GAS1 | rs111548894 | promoter | 0.02 | 0.01 | 4.48 (2.03–9.89) | 2.1 × 10−4 | ||||
| 11q12.2 *h | CD6 | rs72928596 | promoter | 0.03 | 0.01 | 2.81 (1.59–4.97) | 3.8 × 10−4 | — | — | — | — |
| 11q23.2 | NCAM1/CD56 | rs17510855 | enhancer | 0.01 | 0.00 | 4.99 (2.11–11.8) | 2.6 × 10−4 | ||||
| 17p13.1 | CD68 | rs9901673 | p.Q254K, eQTL−s | 0.14 | 0.19 | 0.61 (0.48–0.79) | 1.1 × 10−4 | — | — | — | — |
| 18q22.2 *h*c | SOCS6 | rs11665533 | promoter | 0.54 | 0.49 | 1.36 (1.15–1.60) | 3.6 × 10−4 | — | — | — | — |
| OPC in all races/ethnicities | |||||||||||
| 2p21 | PRKCE | rs2711286 | intron | 0.21 | 0.23 | 0.81 (0.72–0.91) | 2.3 × 10−5 | 0.94 (0.83–1.07) | 0.3489 | 0.83 (0.70–1.04) | 0.0053 |
| 4q12 *c | cKIT/CD117 | rs2646357 | 3′ flanking | 0.48 | 0.44 | 1.19 (1.08–1.30) | 2.3 × 10−5 | 0.97 (0.89–1.07) | 0.5762 | 1.11 (0.96–1.27) | 0.0061 |
| 6p21.32 *h*c | HLA-DRB5 | rs111834747 | promoter | 0.37 | 0.29 | 1.35 (1.20–1.52) | 3.7 × 10−7 | 1.33 (1.22–1.46) | 3.3 × 10−10 | 1.35 (1.20–1.55) | 9.7 × 10−11 |
| HLA-DRB1 | rs28724008 | intron | 0.38 | 0.30 | 1.38 (1.23–1.55) | 3.4 × 10−8 | 1.35 (1.22–1.48) | 9.8 × 10−10 | 1.37 (1.22–1.58) | 2.8 × 10−11 | |
| · | HLA-DQB1 | rs3135006 | intergenic, eQTL−l-s | 0.09 | 0.12 | 0.70 (0.61–0.82) | 2.9 × 10−8 | 0.71 (0.64–0.78) | 4.6 × 10−11 | 0.70 (0.60–0.83) | 5.1 × 10−12 |
| Non-OPC in all races/ethnicities | |||||||||||
| 1p36.32 *h*c | TP73 | rs1122723 | intron | 0.40 | 0.44 | 0.84 (0.76–0.92) | 9.1 × 10−6 | 0.93 (0.83–1.03) | 0.2061 | 0.86 (0.75–1.03) | 0.0031 |
| 3p25.3 | IRAK2 | rs6442161 | intron, eQTL−l-s | 0.40 | 0.37 | 1.18 (1.08–1.29) | 3.4 × 10−5 | 1.09 (0.97–1.21) | 0.1092 | 1.15 (1.00–1.29) | 0.0022 |
| 10q26 *h | DMBT1 | rs17103659 | intergenic | 0.12 | 0.16 | 0.81 (0.72–0.91) | 4.8 × 10−5 | 0.81 (0.66–0.98) | 0.0393 | 0.80 (0.64–0.98) | 1.3 × 10−4 |
| 15q22.2 | TPM1 | rs72743223 | intron | 0.10 | 0.09 | 1.31 (1.13–1.52) | 4.2 × 10−5 | 1.17 (1.00–1.36) | 0.0534 | 1.26 (1.01–1.48) | 2.0 × 10−4 |
| 16q24.3 | FANCA | rs12931267 | intron, eQTL−l-s | 0.08 | 0.07 | 1.21 (1.11–1.32) | 1.2 × 10−5 | 1.10 (0.85–1.40) | 0.4726 | 1.15 (0.98–1.39) | 0.0062 |
Note: *, Known GWAS loci for HNSCC as *h; **, known loci for cervical cancer as *c.
Abbreviations: ID, RefSNP identification number; UTR, untranslated region; TSS, transcriptional start site.
aSNP functional regulatory features (transcriptional enhancer, promoter, transcriptional start site) were predicted by the Encyclopedia of DNA Elements (ENCODE). The eQTLs were retrieved from the GTEx catalog, based on RNA-seq analysis for normal lung (eQTL−l) and squamous esophagus (eQTL−s) tissues, which best represent oropharyngeal and oral cavity tissue.
bIn the discovery (MVP-HNSCC study), the regression models and P values were adjusted for age, sex, genetically Harmonized Ancestry and Race/Ethnicity (HARE), smoking status, alcohol abuse, and BMI category. In the validation (MDACC-HNSCC study), only age, sex, and the principal components (eigenvectors) were adjusted. Variants remaining significant (P meta ≤ 4.95 × 10−4) in the meta-analysis were bolded.