Associations between genetic polymorphisms and non-Hodgkin lymphoma, by lymphoma subtype
| Exposure . | Controls,N† . | All NHL combined* . | DLBCL . | Follicular lymphoma . | Marginal zone lymphoma . | CLL/SLL . | P homo-geneity . | Lowest P value from pairwise analysis§ . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | ||||
| TNF G-308A, rs1800629 | |||||||||||||
| GG | 696 | 799 | 1.0 (reference) | 236 | 1.0 (reference) | 196 | 1.0 (reference) | 64 | 1.0 (reference) | 94 | 1.0 (reference) | ||
| GA | 207 | 298 | 1.3 (1.0, 1.6) | 102 | 1.5 (1.1, 2.0) | 67 | 1.1 (0.8, 1.6) | 23 | 1.3 (0.8, 2.2) | 23 | 0.8 (0.5, 1.3) | ||
| AA | 18 | 38 | 2.0 (1.1, 3.6) | 16 | 2.9 (1.4, 5.8) | 7 | 1.4 (0.6, 3.5) | 5 | 3.6 (1.3, 10.2) | 1 | 0.4 (0.1, 3.1) | ||
| P trend | .002 | <.001 | .3 | .03 | .2 | ||||||||
| GA+AA | 225 | 336 | 1.3 (1.1, 1.6) | 118 | 1.6 (1.2, 2.1) | 74 | 1.2 (0.9, 1.6) | 28 | 1.5 (0.9, 2.4) | 24 | 0.8 (0.5, 1.2) | .04 | DLBCL, MZ vs FL, CLL/SLL; P = .002 |
| IL10 T-3575A, rs1800890 | |||||||||||||
| TT | 379 | 446 | 1.0 (reference) | 134 | 1.0 (reference) | 98 | 1.0 (reference) | 44 | 1.0 (reference) | 49 | 1.0 (reference) | ||
| TA | 401 | 518 | 1.1 (0.9, 1.4) | 165 | 1.2 (0.9, 1.6) | 129 | 1.2 (0.9, 1.7) | 38 | 0.9 (0.5, 1.4) | 45 | 0.9 (0.6, 1.3) | ||
| AA | 130 | 164 | 1.1 (0.8, 1.4) | 54 | 1.1 (0.8, 1.7) | 41 | 1.2 (0.8, 1.8) | 10 | 0.7 (0.4, 1.5) | 23 | 1.3 (0.7, 2.2) | ||
| P trend | .4 | .3 | .3 | .3 | .6 | ||||||||
| TA+AA | 531 | 682 | 1.1 (0.9, 1.3) | 219 | 1.2 (0.9, 1.5) | 170 | 1.2 (0.9, 1.6) | 48 | 0.8 (0.5, 1.3) | 68 | 1.0 (0.6, 1.4) | .3 | DLBCL, FL vs MZ, CLL/SLL; P = .08 |
| FCGR2A Ex4-120G>A, R165H, rs1801274 | |||||||||||||
| GG | 242 | 237 | 1.0 (reference) | 78 | 1.0 (reference) | 51 | 1.0 (reference) | 19 | 1.0 (reference) | 23 | 1.0 (reference) | ||
| AG | 430 | 539 | 1.3 (1.0, 1.6) | 164 | 1.2 (0.8, 1.6) | 135 | 1.4 (1.0, 2.1) | 40 | 1.2 (0.7, 2.1) | 60 | 1.5 (0.9, 2.4) | ||
| AA | 227 | 335 | 1.5 (1.1, 1.9) | 102 | 1.3 (0.9, 1.9) | 79 | 1.5 (1.0, 2.3) | 31 | 1.7 (0.9, 3.1) | 32 | 1.5 (0.8, 2.7) | ||
| P trend | .004 | .1 | .04 | .08 | .2 | ||||||||
| AG+AA | 657 | 874 | 1.3 (1.1, 1.6) | 266 | 1.2 (0.9, 1.6) | 214 | 1.5 (1.0, 2.1) | 71 | 1.4 (0.8, 2.3) | 92 | 1.5 (0.9, 2.4) | .8 | FL vs DLBCL, MZ, CLL/SLL; P = .09 |
| RAG1 Ex2+2473A>G, K820R, rs2227973 | |||||||||||||
| AA | 695 | 810 | 1.0 (reference) | 258 | 1.0 (reference) | 190 | 1.0 (reference) | 59 | 1.0 (reference) | 86 | 1.0 (reference) | ||
| AG | 179 | 246 | 1.1 (0.9, 1.4) | 73 | 1.1 (0.8, 1.5) | 57 | 1.2 (0.8, 1.7) | 29 | 1.7 (1.1, 2.8) | 26 | 1.2 (0.8, 2.0) | ||
| GG | 17 | 35 | 1.8 (1.0, 3.4) | 7 | 1.4 (0.5, 3.4) | 10 | 2.8 (1.2, 6.4) | 4 | 2.0 (0.6, 6.5) | 3 | 1.8 (0.5, 6.7) | ||
| P trend | .05 | .4 | .05 | .02 | .3 | ||||||||
| AG+GG | 196 | 281 | 1.2 (1.0, 1.5) | 80 | 1.1 (0.8, 1.5) | 67 | 1.3 (0.9, 1.8) | 33 | 1.8 (1.1, 2.8) | 29 | 1.3 (0.8, 2.0) | .3 | MZ vs DLBCL, FL, CLL/SLL; P = .03 |
| LIG4 Ex3+54C>T, T9I, rs1805388 | |||||||||||||
| CC | 611 | 788 | 1.0 (reference) | 247 | 1.0 (reference) | 197 | 1.0 (reference) | 67 | 1.0 (reference) | 70 | 1.0 (reference) | ||
| CT | 267 | 299 | 0.9 (0.7, 1.0) | 89 | 0.8 (0.6, 1.1) | 67 | 0.8 (0.6, 1.0) | 23 | 0.8 (0.5, 1.3) | 39 | 1.3 (0.8, 2.0) | ||
| TT | 26 | 18 | 0.5 (0.3, 1.0) | 6 | 0.6 (0.2, 1.4) | 2 | 0.2 (0.1, 0.9) | 0 | ∼ | 5 | 1.7 (0.6, 4.6) | ||
| P trend | .02 | .07 | .01 | .09 | .1 | ||||||||
| CT+TT | 293 | 317 | 0.8 (0.7, 1.0) | 95 | 0.8 (0.6, 1.0) | 69 | 0.7 (0.5, 1.0) | 23 | 0.7 (0.4, 1.2) | 44 | 1.3 (0.9, 2.0) | .06 | DLBCL, FL vs MZ, CLL/SLL; P = .02 |
| XRCC1 Ex6-22C>T, R194W, rs1799782 | |||||||||||||
| CC | 782 | 911 | 1.0 (reference) | 287 | 1.0 (reference) | 217 | 1.0 (reference) | 72 | 1.0 (reference) | 91 | 1.0 (reference) | ||
| CT | 112 | 186 | 1.4 (1.1, 1.8) | 52 | 1.2 (0.9, 1.8) | 41 | 1.3 (0.9, 1.9) | 19 | 1.8 (1.0, 3.0) | 24 | 2.0 (1.2, 3.3) | ||
| TT | 7 | 9 | 1.2 (0.4, 3.2) | 4 | 1.7 (0.5, 6.0) | 4 | 2.6 (0.7, 9.0) | 0 | ∼ | 0 | ∼ | ||
| P trend | .01 | .2 | .07 | .2 | .03 | ||||||||
| CT+TT | 119 | 195 | 1.4 (1.1, 1.8) | 56 | 1.3 (0.9, 1.8) | 45 | 1.4 (0.9, 2.0) | 19 | 1.6 (0.9, 2.8) | 24 | 1.9 (1.1, 3.1) | .5 | CLL/SLL vs DLBCL, FL, MZ; P = .06 |
| MGMT Ex7+13A>G, I143V, rs2308321 | |||||||||||||
| AA | 722 | 861 | 1.0 (reference) | 271 | 1.0 (reference) | 192 | 1.0 (reference) | 76 | 1.0 (reference) | 91 | 1.0 (reference) | ||
| AG | 166 | 234 | 1.1 (0.9, 1.4) | 67 | 1.0 (0.7, 1.4) | 67 | 1.4 (1.0, 1.9) | 13 | 0.7 (0.4, 1.4) | 23 | 1.0 (0.6, 1.7) | ||
| GG | 10 | 14 | 1.1 (0.5, 2.4) | 4 | 0.9 (0.3, 3.0) | 5 | 1.6 (0.5, 4.7) | 1 | 1.0 (0.1, 7.9) | 2 | 1.5 (0.3, 7.0) | ||
| P trend | .4 | .9 | .06 | .4 | .8 | ||||||||
| AG+GG | 176 | 248 | 1.1 (0.9, 1.4) | 71 | 1.0 (0.7, 1.4) | 72 | 1.4 (1.0, 1.9) | 14 | 0.8 (0.4, 1.4) | 25 | 1.0 (0.6, 1.7) | .3 | FL vs DLBCL, MZ, CLL/SLL; P = .05 |
| NAT1 | |||||||||||||
| Any/any | 454 | 546 | 1.0 (reference) | 166 | 1.0 (reference) | 137 | 1.0 (reference) | 41 | 1.0 (reference) | 57 | 1.0 (reference) | ||
| *10/any | 251 | 303 | 1.1 (0.9, 1.3) | 106 | 1.2 (0.9, 1.7) | 59 | 0.9 (0.6, 1.2) | 25 | 1.1 (0.6, 1.8) | 36 | 1.2 (0.8, 1.9) | ||
| *10/*10 | 41 | 66 | 1.6 (1.0, 2.4) | 18 | 1.4 (0.8, 2.6) | 19 | 2.0 (1.1, 3.6) | 5 | 1.4 (0.5, 4.0) | 4 | 0.9 (0.3, 2.7) | ||
| P trend | .1 | .1 | .4 | .5 | .6 | ||||||||
| *10/any + *10/*10 | 292 | 369 | 1.1 (0.9, 1.4) | 124 | 1.3 (0.9, 1.7) | 78 | 1.0 (0.7, 1.4) | 30 | 1.1 (0.7, 1.9) | 40 | 1.2 (0.8, 1.9) | .6 | DLBCL, CLL/SLL vs FL, MZ; P = .07 |
| NAT2 | |||||||||||||
| Slow | 452 | 522 | 1.0 (reference) | 172 | 1.0 (reference) | 113 | 1.0 (reference) | 37 | 1.0 (reference) | 59 | 1.0 (reference) | ||
| Intermediate | 306 | 390 | 1.2 (1.0, 1.4) | 114 | 1.0 (0.8, 1.4) | 103 | 1.5 (1.1, 2.0) | 44 | 1.8 (1.1, 2.8) | 39 | 1.0 (0.7, 1.6) | ||
| Rapid | 50 | 72 | 1.4 (1.0, 2.2) | 25 | 1.5 (0.9, 2.6) | 16 | 1.5 (0.8, 2.8) | 1 | 0.2 (0.0, 1.8) | 7 | 1.4 (0.6, 3.3) | ||
| P trend | .03 | .2 | .02 | .4 | .5 | ||||||||
| Intermediate/rapid | 356 | 462 | 1.2 (1.0, 1.5) | 139 | 1.1 (0.8, 1.5) | 119 | 1.5 (1.1, 2.0) | 45 | 1.6 (1.0, 2.5) | 46 | 1.1 (0.7, 1.7) | .3 | FL vs DLBCL, MZ, CLL/SLL; P = .02 |
| Exposure . | Controls,N† . | All NHL combined* . | DLBCL . | Follicular lymphoma . | Marginal zone lymphoma . | CLL/SLL . | P homo-geneity . | Lowest P value from pairwise analysis§ . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | N† . | OR (95% CI)‡ . | ||||
| TNF G-308A, rs1800629 | |||||||||||||
| GG | 696 | 799 | 1.0 (reference) | 236 | 1.0 (reference) | 196 | 1.0 (reference) | 64 | 1.0 (reference) | 94 | 1.0 (reference) | ||
| GA | 207 | 298 | 1.3 (1.0, 1.6) | 102 | 1.5 (1.1, 2.0) | 67 | 1.1 (0.8, 1.6) | 23 | 1.3 (0.8, 2.2) | 23 | 0.8 (0.5, 1.3) | ||
| AA | 18 | 38 | 2.0 (1.1, 3.6) | 16 | 2.9 (1.4, 5.8) | 7 | 1.4 (0.6, 3.5) | 5 | 3.6 (1.3, 10.2) | 1 | 0.4 (0.1, 3.1) | ||
| P trend | .002 | <.001 | .3 | .03 | .2 | ||||||||
| GA+AA | 225 | 336 | 1.3 (1.1, 1.6) | 118 | 1.6 (1.2, 2.1) | 74 | 1.2 (0.9, 1.6) | 28 | 1.5 (0.9, 2.4) | 24 | 0.8 (0.5, 1.2) | .04 | DLBCL, MZ vs FL, CLL/SLL; P = .002 |
| IL10 T-3575A, rs1800890 | |||||||||||||
| TT | 379 | 446 | 1.0 (reference) | 134 | 1.0 (reference) | 98 | 1.0 (reference) | 44 | 1.0 (reference) | 49 | 1.0 (reference) | ||
| TA | 401 | 518 | 1.1 (0.9, 1.4) | 165 | 1.2 (0.9, 1.6) | 129 | 1.2 (0.9, 1.7) | 38 | 0.9 (0.5, 1.4) | 45 | 0.9 (0.6, 1.3) | ||
| AA | 130 | 164 | 1.1 (0.8, 1.4) | 54 | 1.1 (0.8, 1.7) | 41 | 1.2 (0.8, 1.8) | 10 | 0.7 (0.4, 1.5) | 23 | 1.3 (0.7, 2.2) | ||
| P trend | .4 | .3 | .3 | .3 | .6 | ||||||||
| TA+AA | 531 | 682 | 1.1 (0.9, 1.3) | 219 | 1.2 (0.9, 1.5) | 170 | 1.2 (0.9, 1.6) | 48 | 0.8 (0.5, 1.3) | 68 | 1.0 (0.6, 1.4) | .3 | DLBCL, FL vs MZ, CLL/SLL; P = .08 |
| FCGR2A Ex4-120G>A, R165H, rs1801274 | |||||||||||||
| GG | 242 | 237 | 1.0 (reference) | 78 | 1.0 (reference) | 51 | 1.0 (reference) | 19 | 1.0 (reference) | 23 | 1.0 (reference) | ||
| AG | 430 | 539 | 1.3 (1.0, 1.6) | 164 | 1.2 (0.8, 1.6) | 135 | 1.4 (1.0, 2.1) | 40 | 1.2 (0.7, 2.1) | 60 | 1.5 (0.9, 2.4) | ||
| AA | 227 | 335 | 1.5 (1.1, 1.9) | 102 | 1.3 (0.9, 1.9) | 79 | 1.5 (1.0, 2.3) | 31 | 1.7 (0.9, 3.1) | 32 | 1.5 (0.8, 2.7) | ||
| P trend | .004 | .1 | .04 | .08 | .2 | ||||||||
| AG+AA | 657 | 874 | 1.3 (1.1, 1.6) | 266 | 1.2 (0.9, 1.6) | 214 | 1.5 (1.0, 2.1) | 71 | 1.4 (0.8, 2.3) | 92 | 1.5 (0.9, 2.4) | .8 | FL vs DLBCL, MZ, CLL/SLL; P = .09 |
| RAG1 Ex2+2473A>G, K820R, rs2227973 | |||||||||||||
| AA | 695 | 810 | 1.0 (reference) | 258 | 1.0 (reference) | 190 | 1.0 (reference) | 59 | 1.0 (reference) | 86 | 1.0 (reference) | ||
| AG | 179 | 246 | 1.1 (0.9, 1.4) | 73 | 1.1 (0.8, 1.5) | 57 | 1.2 (0.8, 1.7) | 29 | 1.7 (1.1, 2.8) | 26 | 1.2 (0.8, 2.0) | ||
| GG | 17 | 35 | 1.8 (1.0, 3.4) | 7 | 1.4 (0.5, 3.4) | 10 | 2.8 (1.2, 6.4) | 4 | 2.0 (0.6, 6.5) | 3 | 1.8 (0.5, 6.7) | ||
| P trend | .05 | .4 | .05 | .02 | .3 | ||||||||
| AG+GG | 196 | 281 | 1.2 (1.0, 1.5) | 80 | 1.1 (0.8, 1.5) | 67 | 1.3 (0.9, 1.8) | 33 | 1.8 (1.1, 2.8) | 29 | 1.3 (0.8, 2.0) | .3 | MZ vs DLBCL, FL, CLL/SLL; P = .03 |
| LIG4 Ex3+54C>T, T9I, rs1805388 | |||||||||||||
| CC | 611 | 788 | 1.0 (reference) | 247 | 1.0 (reference) | 197 | 1.0 (reference) | 67 | 1.0 (reference) | 70 | 1.0 (reference) | ||
| CT | 267 | 299 | 0.9 (0.7, 1.0) | 89 | 0.8 (0.6, 1.1) | 67 | 0.8 (0.6, 1.0) | 23 | 0.8 (0.5, 1.3) | 39 | 1.3 (0.8, 2.0) | ||
| TT | 26 | 18 | 0.5 (0.3, 1.0) | 6 | 0.6 (0.2, 1.4) | 2 | 0.2 (0.1, 0.9) | 0 | ∼ | 5 | 1.7 (0.6, 4.6) | ||
| P trend | .02 | .07 | .01 | .09 | .1 | ||||||||
| CT+TT | 293 | 317 | 0.8 (0.7, 1.0) | 95 | 0.8 (0.6, 1.0) | 69 | 0.7 (0.5, 1.0) | 23 | 0.7 (0.4, 1.2) | 44 | 1.3 (0.9, 2.0) | .06 | DLBCL, FL vs MZ, CLL/SLL; P = .02 |
| XRCC1 Ex6-22C>T, R194W, rs1799782 | |||||||||||||
| CC | 782 | 911 | 1.0 (reference) | 287 | 1.0 (reference) | 217 | 1.0 (reference) | 72 | 1.0 (reference) | 91 | 1.0 (reference) | ||
| CT | 112 | 186 | 1.4 (1.1, 1.8) | 52 | 1.2 (0.9, 1.8) | 41 | 1.3 (0.9, 1.9) | 19 | 1.8 (1.0, 3.0) | 24 | 2.0 (1.2, 3.3) | ||
| TT | 7 | 9 | 1.2 (0.4, 3.2) | 4 | 1.7 (0.5, 6.0) | 4 | 2.6 (0.7, 9.0) | 0 | ∼ | 0 | ∼ | ||
| P trend | .01 | .2 | .07 | .2 | .03 | ||||||||
| CT+TT | 119 | 195 | 1.4 (1.1, 1.8) | 56 | 1.3 (0.9, 1.8) | 45 | 1.4 (0.9, 2.0) | 19 | 1.6 (0.9, 2.8) | 24 | 1.9 (1.1, 3.1) | .5 | CLL/SLL vs DLBCL, FL, MZ; P = .06 |
| MGMT Ex7+13A>G, I143V, rs2308321 | |||||||||||||
| AA | 722 | 861 | 1.0 (reference) | 271 | 1.0 (reference) | 192 | 1.0 (reference) | 76 | 1.0 (reference) | 91 | 1.0 (reference) | ||
| AG | 166 | 234 | 1.1 (0.9, 1.4) | 67 | 1.0 (0.7, 1.4) | 67 | 1.4 (1.0, 1.9) | 13 | 0.7 (0.4, 1.4) | 23 | 1.0 (0.6, 1.7) | ||
| GG | 10 | 14 | 1.1 (0.5, 2.4) | 4 | 0.9 (0.3, 3.0) | 5 | 1.6 (0.5, 4.7) | 1 | 1.0 (0.1, 7.9) | 2 | 1.5 (0.3, 7.0) | ||
| P trend | .4 | .9 | .06 | .4 | .8 | ||||||||
| AG+GG | 176 | 248 | 1.1 (0.9, 1.4) | 71 | 1.0 (0.7, 1.4) | 72 | 1.4 (1.0, 1.9) | 14 | 0.8 (0.4, 1.4) | 25 | 1.0 (0.6, 1.7) | .3 | FL vs DLBCL, MZ, CLL/SLL; P = .05 |
| NAT1 | |||||||||||||
| Any/any | 454 | 546 | 1.0 (reference) | 166 | 1.0 (reference) | 137 | 1.0 (reference) | 41 | 1.0 (reference) | 57 | 1.0 (reference) | ||
| *10/any | 251 | 303 | 1.1 (0.9, 1.3) | 106 | 1.2 (0.9, 1.7) | 59 | 0.9 (0.6, 1.2) | 25 | 1.1 (0.6, 1.8) | 36 | 1.2 (0.8, 1.9) | ||
| *10/*10 | 41 | 66 | 1.6 (1.0, 2.4) | 18 | 1.4 (0.8, 2.6) | 19 | 2.0 (1.1, 3.6) | 5 | 1.4 (0.5, 4.0) | 4 | 0.9 (0.3, 2.7) | ||
| P trend | .1 | .1 | .4 | .5 | .6 | ||||||||
| *10/any + *10/*10 | 292 | 369 | 1.1 (0.9, 1.4) | 124 | 1.3 (0.9, 1.7) | 78 | 1.0 (0.7, 1.4) | 30 | 1.1 (0.7, 1.9) | 40 | 1.2 (0.8, 1.9) | .6 | DLBCL, CLL/SLL vs FL, MZ; P = .07 |
| NAT2 | |||||||||||||
| Slow | 452 | 522 | 1.0 (reference) | 172 | 1.0 (reference) | 113 | 1.0 (reference) | 37 | 1.0 (reference) | 59 | 1.0 (reference) | ||
| Intermediate | 306 | 390 | 1.2 (1.0, 1.4) | 114 | 1.0 (0.8, 1.4) | 103 | 1.5 (1.1, 2.0) | 44 | 1.8 (1.1, 2.8) | 39 | 1.0 (0.7, 1.6) | ||
| Rapid | 50 | 72 | 1.4 (1.0, 2.2) | 25 | 1.5 (0.9, 2.6) | 16 | 1.5 (0.8, 2.8) | 1 | 0.2 (0.0, 1.8) | 7 | 1.4 (0.6, 3.3) | ||
| P trend | .03 | .2 | .02 | .4 | .5 | ||||||||
| Intermediate/rapid | 356 | 462 | 1.2 (1.0, 1.5) | 139 | 1.1 (0.8, 1.5) | 119 | 1.5 (1.1, 2.0) | 45 | 1.6 (1.0, 2.5) | 46 | 1.1 (0.7, 1.7) | .3 | FL vs DLBCL, MZ, CLL/SLL; P = .02 |
CLL/SLL indicates chronic lymphocytic leukemia/small lymphocytic lymphoma; DLBCL, diffuse large B-cell lymphoma; LIG4, DNA ligase IV; FCGR2A, Fc-gamma receptor IIA; FL, follicular lymphoma; IL10, interleukin-10; MZ, marginal zone lymphoma; MGMT, O-6-methylguanine DNA methyltransferase; NAT, N-acetyltransferase; NHL, non-Hodgkin lymphoma; RAG1, recombination-activating gene 1; TNF, tumor necrosis factor; and XRCC1, X-ray repair cross-complementing 1.
Includes all NHL cases in the study, regardless of histologic subtype (N = 1320, excludes one DLBCL case resulting from missing data on education).
Counts may not sum to the total because of missing data. For some exposures (see Table 1), a split-sample design was used so that only approximately 50% of participants were expected to provide information.
Odds ratios (95% CIs) estimated using polytomous logistic regression models, adjusted for age, sex, race, study center, and education.
To account for the seven comparisons within the pairwise analysis, we applied a Bonferroni correction and considered P values < 0.007 to be statistically significant.