Table 4.
Interaction between cigarette smoking, estrogen status, and NSAID use with JAK, STAT, TYK and cancer risk
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| Gene | SNP (Model)1 | Variant2 | Wildtype | Interaction P Value | p_ACT | ||||
| OR | (95% CI) | OR | (95% CI) | OR | (95% CI) | ||||
| Colon Cancer | No Recent Aspirin/NSAID Use | Recent Aspirin/NSAID Use | |||||||
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| TYK2 | rs280521 (D) | 1.00 | (0.82, 1.21) | 0.49 | (0.38, 0.64) | 0.72 | (0.61, 0.84) | 0.0266 | 0.1146 |
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| No Recent Estrogen | Estrogen Use | ||||||||
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| STAT1 | rs10199181 (R) | 1.19 | (0.85, 1.67) | 0.37 | (0.23, 0.62) | 0.65 | (0.50, 0.85) | 0.0171 | 0.1406 |
| rs10208033 (A) | 1.35 | (0.93, 1.96) | 0.39 | (0.23, 0.65) | 0.66 | (0.44, 0.98) | 0.0405 | 0.2628 | |
| rs2280233 (A) | 0.78 | (0.54, 1.11) | 0.58 | (0.37, 0.90) | 0.37 | (0.25, 0.56) | 0.0138 | 0.1239 | |
| rs3771300 (A) | 0.70 | (0.49, 1.00) | 0.58 | (0.37, 0.89) | 0.37 | (0.24, 0.57) | 0.0081 | 0.0805 | |
| rs7562024 (A) | 1.44 | (0.97, 2.12) | 0.48 | (0.29, 0.78) | 0.71 | (0.48, 1.04) | 0.0322 | 0.2250 | |
| STAT4 | rs6572770 (A) | 1.33 | (0.83, 2.11) | 0.40 | (0.20, 0.79) | 0.70 | (0.51, 0.98) | 0.0345 | 0.3578 |
| TYK2 | rs280519 (R) | 1.50 | (1.12, 2.01) | 0.59 | (0.39, 0.89) | 0.66 | (0.50, 0.87) | 0.0403 | 0.1705 |
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| Non Smoker | Recent Smoker | ||||||||
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| JAK2 | rs10815160 (R) | 1.17 | (0.87, 1.58) | 3.15 | (1.60, 6.22) | 1.11 | (0.93, 1.32) | 0.0166 | 0.0869 |
| rs1887429 (D) | 0.79 | (0.68, 0.92) | 1.16 | (0.90, 1.48) | 0.94 | (0.75, 1.19) | 0.0131 | 0.0873 | |
| rs7043371 (A) | 1.21 | (0.98, 1.49) | 1.12 | (0.80, 1.57) | 1.67 | (1.19, 2.34) | 0.015 | 0.0895 | |
| STAT2 | rs2229363 (D) | 1.20 | (0.74, 1.95) | 0.39 | (0.14, 1.07) | 1.20 | (1.01, 1.43) | 0.0156 | 0.0302 |
| STAT4 | rs4853540 (A) | 1.21 | (0.86, 1.68) | 0.79 | (0.42, 1.48) | 1.33 | (1.07, 1.66) | 0.0304 | 0.3310 |
| STAT5A | rs7217728 (A) | 1.15 | (0.89, 1.49) | 2.39 | (1.44, 3.96) | 0.98 | (0.76, 1.26) | 0.0098 | 0.0177 |
| STAT5B | rs7218563 (A) | 1.14 | (0.88, 1.47) | 2.30 | (1.39, 3.83) | 0.97 | (0.76, 1.25) | 0.0151 | 0.0398 |
| STAT6 | rs3024974 (D) | 0.88 | (0.72, 1.06) | 1.48 | (1.02, 2.15) | 1.07 | (0.89, 1.30) | 0.0465 | 0.1709 |
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| Rectal Cancer | No Recent Aspirin/NSAID Use | Recent Aspirin/NSAID Use | |||||||
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| JAK2 | rs10815160 (A) | 1.52 | (0.92, 2.51) | 0.49 | (0.26, 0.91) | 0.82 | (0.63, 1.07) | 0.019 | 0.1149 |
| STAT6 | rs324011 (D) | 1.48 | (1.14, 1.92) | 0.86 | (0.65, 1.14) | 0.94 | (0.68, 1.30) | 0.0207 | 0.0782 |
| TYK2 | rs280521 (D) | 1.40 | (1.05, 1.85) | 0.62 | (0.44, 0.88) | 0.82 | (0.65, 1.03) | 0.0092 | 0.0418 |
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| No Recent Estrogen | Estrogen Use | ||||||||
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| JAK1 | rs2256298 (A) | 0.38 | (0.14, 1.05) | 0.94 | (0.44, 2.02) | 0.55 | (0.35, 0.85) | 0.0427 | 0.1931 |
| rs310198 (D) | 0.69 | (0.40, 1.19) | 0.81 | (0.49, 1.34) | 0.54 | (0.37, 0.79) | 0.0276 | 0.1402 | |
| rs310199 (A) | 0.75 | (0.34, 1.62) | 1.01 | (0.50, 2.06) | 0.44 | (0.27, 0.71) | 0.0136 | 0.0837 | |
| rs310211 (A) | 0.32 | (0.12, 0.80) | 0.84 | (0.42, 1.69) | 0.51 | (0.32, 0.82) | 0.0138 | 0.0790 | |
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| Non Smoker | Recent Smoker | ||||||||
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| STAT2 | rs2229363 (D) | 1.74 | (0.86, 3.54) | 0.23 | (0.03, 1.92) | 1.36 | (1.05, 1.76) | 0.016 | 0.0309 |
1
Models: A - additive or co-dominant; D - dominant
2
Heterozygote/variant genotype if dominant model; variant if recessive or additive (or co-dominant); all comparisons are made to non-user/smoker and wildtype genotype