Table 3.
SNP hazard ratios, dominant genetic model (adjusted p-values < 0.05 are highlighted).
| DEATH FROM ALL CAUSES |
DEATH FROM HEAD AND NECK CANCER |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Model:SNP unadjusted Complete case analysis n=1227 for mostc SNPs |
Model: SNP & covariatesa Complete case analysis n=1050for mostc SNPs |
Model: SNP & covariatesa summary from 25 imputations n=1227 for all SNPs |
Model: SNP unadjusted Complete case analysis n=1227 for mostc SNPs |
Model: SNP & covariatesb Complete case analysis n=1050 for mostc SNPs |
Model: SNP & covariatesb summ ary f rom 25 impu tation s n=1227 for all SNPs |
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| Gene | SNP name | major/ minor allele |
allele frequency (any minor/only major/missing) |
HRd (95% CI) | Bonferroni- corrected p- value (64 tests) (highlighted if <0 05) |
HRd (95% CI) | Bonferroni- correctedp- value (64 tests) (highlighted if <0 05) |
HRd (95% CI) | Bonferroni- corrected p- value (64 tests) (highlighted if <0 05) |
HRd (95% CI) | Bonferroni- corrected p- value (64 tests) (highlighted if <0 05) |
HRd (95% CI) | Bonferroni- corrected p- value (64 tests) (highlighted if <0 05) |
HRd (95% CI) | Bonferroni- corrected p- value (64 tests) (highlighted if <0 05) |
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ALCOHOL METABOLISM GENES
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| ADH1B | rs12507573 | C/A | 855/372/0 | 0.95 (0.80-1.14) | 1 | 1.11 (0.91-1.36) | 1 | 1.05 (0.87-1.27) | 1 | 1.05 (0.79–1.39) | 1 | 1.07 (0.77-1.49) | 1 | 1.12 (0.83-1.50) | 1 |
| rs1042026 | A/G | 512/715/0 | 0.92 (0.78-1.10) | 1 | 1.02 (0.84-1.23) | 1 | 1.01 (0.85-1.20) | 1 | 1.05 (0.81-1.37) | 1 | 1.10 (0.81-1.51) | 1 | 1.04 (0.79-1.36) | 1 | |
| rs7673353 | C/T | 99/1128/0 | 1.20 (0.89-1.62) | 1 | 0.90 (0.65-1.25) | 1 | 0.95 (0.70-1.30) | 1 | 1.14 (0.71-1.82) | 1 | 1.11 (0.61-2.03) | 1 | 1.02 (0.59-1.78) | 1 | |
| rs17028834 | T/C | 86/1141/0 | 1.38 (1.03-1.87) | 1 | 1.03 (0.74-1.44) | 1 | 1.11 (0.82-1.51) | 1 | 1.25 (0.77-2.03) | 1 | 1.25 (0.68-2.27) | 1 | 1.30 (0.74-2.27) | 1 | |
| rs1693457 | T/C | 421/805/1 | 0.91 (0.76-1.08) | 1 | 0.87 (0.71-1.06) | 1 | 0.89 (0.75-1.07) | 1 | 0.89 (0.67-1.17) | 1 | 0.94 (0.68-1.30) | 1 | 0.90 (0.68-1.20) | 1 | |
| rs1229984 | G/A | 31/1196/0 | 0.59 (0.30-1.13) | 1 | 0.65 (0.27-1.57) | 1 | 0.76 (0.39-1.48) | 1 | 0.78 (0.32-1.90) | 1 | 0.70 (0.17-2.84) | 1 | 0.95 (0.38-2.33) | 1 | |
| rs1159918 | G/T | 825/402/0 | 1.08 (0.90-1.29) | 1 | 0.91 (0.75-1.11) | 1 | 0.99 (0.82-1.19) | 1 | 0.97 (0.74-1.28) | 1 | 0.93 (0.67-1.30) | 1 | 0.97 (0.72-1.30) | 1 | |
| rs1229982 | G/T | 527/700/0 | 1.12 (0.95-1.33) | 1 | 0.95 (0.78-1.14) | 1 | 1.06 (0.89-1.25) | 1 | 0.94 (0.72-1.23) | 1 | 0.89 (0.64-1.23) | 1 | 0.96 (0.72-1.27) | 1 | |
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| ADH1C | rs2298753 | T/C | 221/1006/0 | 0.82 (0.65-1.02) | 1 | 0.87 (0.68-1.12) | 1 | 0.85 (0.68-1.07) | 1 | 0.89 (0.63-1.26) | 1 | 0.99 (0.67-1.46) | 1 | 0.91 (0.64-1.29) | 1 |
| rs1614972 | C/T | 687/540/0 | 0.93 (0.79-1.10) | 1 | 0.84 (0.70-1.01) | 1 | 0.88 (0.74-1.04) | 1 | 0.84 (0.65-1.09) | 1 | 0.82 (0.61-1.11) | 1 | 0.84 (0.64-1.09) | 1 | |
| rs1391088 | C/A | 178/1049/0 | 0.93 (0.73-1.18) | 1 | 0.86 (0.65-1.13) | 1 | 0.95 (0.74-1.22) | 1 | 0.94 (0.65-1.37) | 1 | 0.82 (0.52-1.30) | 1 | 1.01 (0.68-1.49) | 1 | |
| rs1693482 | C/T | 695/530/2 | 0.90 (0.76-1.07) | 1 | 1.07 (0.89-1.29) | 1 | 1.03 (0.86-1.22) | 1 | 0.95 (0.73-1.24) | 1 | 1.06 (0.78-1.45) | 1 | 1.06 (0.80-1.40) | 1 | |
| rs1631460 | C/G | 704/522/1 | 0.89 (0.75-1.05) | 1 | 1.06 (0.88-1.28) | 1 | 1.02 (0.86-1.21) | 1 | 0.95 (0.73-1.23) | 1 | 1.06 (0.77-1.45) | 1 | 1.06 (0.80-1.39) | 1 | |
| rs11936869 | C/G | 614/613/0 | 0.95 (0.81-1.13) | 1 | 0.90 (0.75-1.08) | 1 | 0.93 (0.78-1.10) | 1 | 0.82 (0.63-1.07) | 1 | 0.85 (0.63-1.16) | 1 | 0.87 (0.66-1.14) | 1 | |
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| ADH4 | rs29001227 | A/T | 105/1122/0 | 1.33(1.01-1.76) | 1 | 1.09 (0.80-1.48) | 1 | 1.12 (0.84-1.49) | 1 | 1.36 (0.89-2.08) | 1 | 1.62 (0.92-2.87) | 1 | 1.64 (0.97-2.75) | 1 |
| rs1126672 | C/T | 505/722/0 | 0.93 (0.79-1.11) | 1 | 1.00 (0.83-1.21) | 1 | 1.02 (0.86-1.22) | 1 | 0.82 (0.62-1.07) | 1 | 0.74 (0.53-1.02) | 1 | 0.81 (0.61-1.07) | 1 | |
| rs4699710 | T/C | 585/642/0 | 1.01 (0.85-1.19) | 1 | 1.07 (0.89-1.30) | 1 | 1.09 (0.92-1.30) | 1 | 0.86 (0.66-1.12) | 1 | 0.79 (0.58-1.07) | 1 | 0.88 (0.67-1.15) | 1 | |
| rs10017466 | T/C | 669/557/1 | 1.07 (0.91-1.27) | 1 | 1.08 (0.89-1.30) | 1 | 1.11 (0.93-1.32) | 1 | 0.97 (0.74-1.25) | 1 | 0.91 (0.68-1.24) | 1 | 0.99 (0.76-1.30) | 1 | |
| rs1800759 | C/A | 870/357/0 | 1.12 (0.93-1.35) | 1 | 1.03 (0.83-1.26) | 1 | 1.04 (0.86-1.26) | 1 | 0.97 (0.73-1.29) | 1 | 0.91 (0.65-1.27) | 1 | 0.91 (0.68-1.23) | 1 | |
| rs1800761 | G/A | 474/753/0 | 1.02 (0.86-1.22) | 1 | 1.01 (0.83-1.22) | 1 | 1.02 (0.86-1.22) | 1 | 1.00 (0.76-1.30) | 1 | 1.00 (0.73-1.37) | 1 | 1.05 (0.79-1.39) | 1 | |
| rs3762894 | T/C | 385/842/0 | 0.97 (0.81-1.17) | 1 | 0.96 (0.79-1.17) | 1 | 0.98 (0.82-1.18) | 1 | 0.97 (0.73-1.29) | 1 | 0.96 (0.69-1.33) | 1 | 1.01 (0.76-1.35) | 1 | |
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| ADH7 | rs284787 | C/T | 484/743/0 | 0.96 (0.81-1.14) | 1 | 1.03 (0.85-1.25) | 1 | 1.06 (0.89-1.26) | 1 | 1.15 (0.88-1.49) | 1 | 1.23 (0.90-1.66) | 1 | 1.32 (1.00-1.72) | 1 |
| rs894369 | C/G | 391/836/0 | 1.15 (0.97-1.37) | 1 | 1.10 (0.91-1.33) | 1 | 1.08 (0.90-1.29) | 1 | 1.06 (0.80-1.39) | 1 | 0.96 (0.70-1.32) | 1 | 0.98 (0.74-1.30) | 1 | |
| rs17588403 | T/A | 388/839/0 | 0.97 (0.81-1.16) | 1 | 1.06 (0.87-1.30) | 1 | 1.02 (0.85-1.22) | 1 | 0.81 (0.61-1.09) | 1 | 0.84 (0.60-1.17) | 1 | 0.79 (0.59-1.07) | 1 | |
| rs1154454 | T/C | 469/758/0 | 1.12 (0.94-1.33) | 1 | 0.99 (0.82-1.20) | 1 | 0.99 (0.83-1.18) | 1 | 1.06 (0.82-1.39) | 1 | 0.97 (0.71-1.34) | 1 | 0.99 (0.74-1.31) | 1 | |
| rs1154456 | T/C | 648/579/0 | 0.86 (0.73-1.02) | 1 | 1.02 (0.84-1.22) | 1 | 0.95 (0.80-1.13) | 1 | 1.06 (0.82-1.38) | 1 | 1.11 (0.81-1.51) | 1 | 1.11 (0.84-1.46) | 1 | |
| rs1154460 | G/A | 895/329/3 | 0.87 (0.72-1.05) | 1 | 0.87 (0.71-1.06) | 1 | 0.83 (0.69-1.00) | 1 | 0.97 (0.72-1.30) | 1 | 0.90 (0.65-1.25) | 1 | 0.95 (0.71-1.27) | 1 | |
| rs971074 | G/A | 281/946/0 | 0.98 (0.80-1.20) | 1 | 0.86 (0.68-1.07) | 1 | 0.90 (0.73-1.10) | 1 | 0.93 (0.68-1.27) | 1 | 0.86 (0.59-1.25) | 1 | 0.88 (0.63-1.23) | 1 | |
| rs1573496 | C/G | 166/1060/1 | 0.82 (0.64-1.07) | 1 | 0.80 (0.60-1.06) | 1 | 0.81 (0.63-1.05) | 1 | 0.85 (0.58-1.27) | 1 | 0.73 (0.45-1.17) | 1 | 0.79 (0.52-1.19) | 1 | |
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| ALDH2 | rs4767939 | A/G | 529/697/1 | 1.12 (0.94-1.32) | 1 | 0.96 (0.79-1.15) | 1 | 1.01 (0.85-1.20) | 1 | 1.07 (0.83-1.40) | 1 | 0.97 (0.72-1.32) | 1 | 1.01 (0.77-1.33) | 1 |
| rs2238151 | T/C | 858/365/4 | 1.18 (0.98-1.43) | 1 | 0.93 (0.75-1.15) | 1 | 0.98 (0.81-1.19) | 1 | 1.16 (0.87-1.55) | 1 | 1.00 (0.70-1.43) | 1 | 1.09 (0.79-1.49) | 1 | |
| rs7312055 | G/A | 144/1083/0 | 1.60 (1.26-2.02) | 0.006 | 1.13(0.87-1.48) | 1 | 1.18 (0.93-1.51) | 1 | 1.29 (0.87-1.91) | 1 | 1.63 (0.92-2.89) | 1 | 1.36 (0.81-2.27) | 1 | |
| rs2158029 | G/A | 57/1170/0 | 1.51 (1.06-2.13) | 1 | 1.07 (0.74-1.57) | 1 | 1.11 (0.78-1.57) | 1 | 0.69 (0.33-1.47) | 1 | 0.62 (0.27-1.46) | 1 | 0.55 (0.25-1.20) | 1 | |
| rs16941667 | C/T | 239/988/0 | 1.05 (0.85-1.29) | 1 | 0.94 (0.75-1.19) | 1 | 0.99 (0.80-1.22) | 1 | 1.25 (0.92-1.70) | 1 | 1.13(0.79-1.61) | 1 | 1.20 (0.87-1.64) | 1 | |
| rs16941669 | T/G | 240/987/0 | 0.87 (0.70-1.08) | 1 | 0.91 (0.72-1.16) | 1 | 0.84 (0.68-1.05) | 1 | 0.91 (0.65-1.28) | 1 | 0.87 (0.59-1.29) | 1 | 0.88 (0.62-1.23) | 1 | |
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| CYP2E1 | rs3813865 | G/C | 125/1102/0 | 1.49 (1.16-1.92) | 0.116 | 1.38 (1.05-1.82) | 1 | 1.43(1.11-1.85) | 0.391 | 1.64 (1.13-2.39) | 0.605 | 2.20 (1.40-3.45) | 0.04 | 2.00 (1.33-3.01) | 0.059 |
| rs3813867 | G/C | 83/1143/1 | 0.80 (0.55-1.14) | 1 | 0.70 (0.48-1.03) | 1 | 0.68 (0.47-0.97) | 1 | 0.89 (0.52-1.53) | 1 | 0.67 (0.36-1.25) | 1 | 0.78 (0.45-1.36) | 1 | |
| rs8192772 | T/C | 200/1026/1 | 1.39 (1.12-1.72) | 0.148 | 1.42 (1.13-1.79) | 0.158 | 1.37 (1.11-1.70) | 0.248 | 1.53(1.12-2.10) | 0.539 | 1.82 (1.28-2.58) | 0.055 | 1.62 (1.17-2.23) | 0.231 | |
| rs915908 | G/A | 250/977/0 | 0.71 (0.56-0.89) | 0.184 | 0.82 (0.64-1.06) | 1 | 0.75 (0.60-0.95) | 0.98 | 0.84 (0.60-1.18) | 1 | 0.90 (0.61-1.34) | 1 | 0.85 (0.60-1.20) | 1 | |
| rs915909 | C/T | 59/1167/1 | 1.30 (0.91-1.86) | 1 | 0.96 (0.65-1.41) | 1 | 0.90 (0.63-1.30) | 1 | 1.14 (0.64-2.04) | 1 | 1.09 (0.55-2.17) | 1 | 0.97 (0.51-1.84) | 1 | |
| rs7092584 | C/T | 263/962/2 | 1.26 (1.04-1.54) | 1 | 1.24 (1.00-1.53) | 1 | 1.22 (1.00-1.48) | 1 | 1.31 (0.97-1.77) | 1 | 1.31 (0.94-1.83) | 1 | 1.31 (0.97-1.77) | 1 | |
| rs743535 | C/T | 249/969/9 | 1.30 (1.06-1.58) | 0.677 | 1.20 (0.97-1.49) | 1 | 1.19 (0.97-1.45) | 1 | 1.47 (1.09-1.99) | 0.694 | 1.37 (0.97-1.93) | 1 | 1.46 (1.08-1.99) | 0.957 | |
| rs2249695 | C/T | 603/623/1 | 1.33(1.13-1.58) | 0.053 | 1.12 (0.92-1.35) | 1 | 1.10 (0.92-1.31) | 1 | 1.37 (1.05-1.78) | 1 | 1.43(1.02-2.00) | 1 | 1.33 (0.98-1.78) | 1 | |
| rs28969387 | A/T | 25/1202 /0 | 1.68(1.02-2.77) | 1 | 0.92(0.51-1.66) | 1 | 1.14(0.69-1.90) | 1 | 2.03(1.00-4.11) | 1 | 0.79(0.28-2.24) | 1 | 1.40(0.66-2.99) | 1 | |
| rs11101812 | T/C | 26/1198 /3 | 0.72(0.37-1.39) | 1 | 0.53(0.26-1.07) | 1 | 0.45(0.23-0.87) | 1 | 0.79(0.29-2.12) | 1 | 0.60(0.18-1.97) | 1 | 0.62(0.22-1.74) | 1 | |
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OXIDATIVE STRESS GENES
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| CAT | rs1049982 | C/T | 703/521/3 | 1.08 (0.91-1.28) | 1 | 1.06 (0.88-1.27) | 1 | 1.06 (0.89-1.26) | 1 | 1.03 (0.79-1.33) | 1 | 1.09 (0.81-1.48) | 1 | 1.06 (0.81-1.39) | 1 |
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| GPx1 | rs8179172 | T/A | 51/1176/0 | 1.51 (1.03-2.21) | 1 | 1.12 (0.74-1.72) | 1 | 1.13 (0.76-1.67) | 1 | 0.86 (0.41-1.83) | 1 | 0.52 (0.20-1.33) | 1 | 0.67 (0.30-1.50) | 1 |
| rs1800668 | C/T | 588/638/1 | 0.93 (0.78-1.10) | 1 | 0.97 (0.81-1.16) | 1 | 0.96 (0.81-1.14) | 1 | 0.87 (0.67-1.12) | 1 | 0.79 (0.58-1.08) | 1 | 0.85 (0.65-1.12) | 1 | |
| rs3811699 | A/G | 614/613/0 | 0.96 (0.82-1.14) | 1 | 0.94 (0.78-1.13) | 1 | 0.95 (0.80-1.13) | 1 | 0.89 (0.69-1.16) | 1 | 0.78 (0.58-1.06) | 1 | 0.86 (0.66-1.12) | 1 | |
| rs3448 | C/T | 578/649/0 | 0.90 (0.76-1.07) | 1 | 0.91 (0.75-1.09) | 1 | 0.87 (0.73-1.03) | 1 | 0.85 (0.65-1.10) | 1 | 0.93 (0.69-1.26) | 1 | 0.81 (0.62-1.05) | 1 | |
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| GPx2 | rs11623705 | G/T | 227/1000/0 | 0.90 (0.72-1.12) | 1 | 0.91 (0.71-1.17) | 1 | 0.93 (0.74-1.16) | 1 | 1.37 (1.01-1.86) | 1 | 1.41 (0.97-2.04) | 1 | 1.39 (1.01-1.91) | 1 |
| rs2412065 | G/C | 529/698/0 | 1.18 (1.00-1.40) | 1 | 1.02 (0.85-1.23) | 1 | 1.03 (0.87-1.23) | 1 | 1.33 (1.03-1.73) | 1 | 1.25 (0.92-1.70) | 1 | 1.26 (0.96-1.66) | 1 | |
| rs2737844 | C/T | 728/494/5 | 1.24 (1.04-1.47) | 1 | 1.07 (0.88-1.30) | 1 | 1.01 (0.85-1.21) | 1 | 1.22 (0.93-1.60) | 1 | 1.22 (0.87-1.71) | 1 | 1.15 (0.85-1.54) | 1 | |
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| GPx4 | rs757229 | G/C | 925/301/1 | 1.03 (0.85-1.26) | 1 | 0.99 (0.80-1.23) | 1 | 1.01 (0.82-1.23) | 1 | 0.95 (0.70-1.27) | 1 | 1.10 (0.78-1.56) | 1 | 0.94 (0.69-1.27) | 1 |
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| SOD1 | rs11910115 | A/C | 62/1165/0 | 1.25 (0.87-1.78) | 1 | 1.15 (0.79-1.68) | 1 | 1.08 (0.75-1.56) | 1 | 1.00 (0.54-1.83) | 1 | 1.25 (0.63-2.51) | 1 | 1.10 (0.57-2.15) | 1 |
| rs4998557 | G/A | 395/831/1 | 1.24 (1.04-1.47) | 1 | 1.07 (0.88-1.30) | 1 | 1.09 (0.91-1.30) | 1 | 1.15 (0.87-1.51) | 1 | 1.08 (0.77-1.50) | 1 | 1.05 (0.78-1.41) | 1 | |
| rs10432782 | T/G | 350/876/1 | 1.25 (1.04-1.49) | 1 | 1.13 (0.93-1.38) | 1 | 1.15 (0.96-1.38) | 1 | 1.29 (0.98-1.70) | 1 | 1.24 (0.90-1.71) | 1 | 1.22 (0.92-1.62) | 1 | |
| rs2070424 | A/G | 222/1005/0 | 1.32 (1.07-1.62) | 0.517 | 1.12 (0.89-1.40) | 1 | 1.17 (0.95-1.44) | 1 | 1.41 (1.03-1.92) | 1 | 1.15 (0.80-1.66) | 1 | 1.30 (0.94-1.80) | 1 | |
| rs1041740 | C/T | 543/684/0 | 0.91 (0.77-1.08) | 1 | 0.96 (0.80-1.16) | 1 | 0.97 (0.82-1.15) | 1 | 0.94 (0.72-1.22) | 1 | 0.88 (0.64-1.20) | 1 | 0.89 (0.68-1.18) | 1 | |
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| SOD2 | rs4342445 | G/A | 473/754/0 | 0.92 (0.77-1.09) | 1 | 1.05 (0.87-1.27) | 1 | 1.01 (0.85-1.21) | 1 | 0.78 (0.59-1.03) | 1 | 0.88 (0.64-1.21) | 1 | 0.87 (0.66-1.16) | 1 |
| rs2842980 | A/T | 510/717/0 | 1.22 (1.03-1.44) | 1 | 1.07 (0.89-1.29) | 1 | 1.16 (0.97-1.37) | 1 | 1.49 (1.15-1.94) | 0.161 | 1.43 (1.05-1.94) | 1 | 1.50 (1.15-1.97) | 0.202 | |
| rs8031 | T/A | 838/389/0 | 0.99 (0.83-1.18) | 1 | 1.05 (0.86-1.29) | 1 | 1.02 (0.85-1.22) | 1 | 1.19 (0.89-1.58) | 1 | 1.12 (0.80-1.56) | 1 | 1.12 (0.83-1.51) | 1 | |
| rs5746134 | C/T | 100/1127/0 | 1.33 (1.00-1.77) | 1 | 0.95 (0.69-1.32) | 1 | 0.99 (0.73-1.33) | 1 | 1.39 (0.90-2.14) | 1 | 1.23 (0.67-2.26) | 1 | 1.36 (0.80-2.32) | 1 | |
| rs2758331 | C/A | 803/424/0 | 0.95 (0.80-1.13) | 1 | 1.09 (0.90-1.33) | 1 | 1.03 (0.86-1.23) | 1 | 1.06 (0.80-1.40) | 1 | 1.10 (0.79-1.52) | 1 | 1.05 (0.78-1.41) | 1 | |
a
Cox models used to calculate hazard ratios for all-cause death included SNP coded for dominant model, anatomical site, T stage, N stage, M stage, angiolymphatic invasion status, treatment (surgery, chemotherapy), presence of comorbid cardiovascular or lung disease, duration of smoking cigarettes (years), reception of at least one routine dental visit in past 10 years.
b
Cox models used to calculate hazard ratios for cancer-specific death included SNP coded for dominant model and all covariates listed above for all-cause death models, plus the following additional variables: radiation treatment, presence of comorbid liver disease or hepatitis, sex, race, age, federal poverty level, ever exposure to environmental tobacco smoke at work, ever loss of a tooth due to disease.
c
These analyses included only those cases who had complete information on the SNP and any covariates in the model. Two-thirds of SNPs (43 of 64) were successfully genotyped for all cases, and 20% of SNPs (n = 13) were missing in only one subject.
d
HRs represent hazard of any minor allele, compared to hazard of homozygous major allele.