Table 1.
Interactions between NSAID use (no, yes) and studied polymorphisms in relation to risk of colorectal cancer in prospective cohorts. Statistically significant interactions between NSAID use and a polymorphism in relation to CRC are shown in bold (Pint < 0.05)
| NSAID | IRR* 95% CI | IRR† 95% CI | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No | Yes | NSAID | NSAID | ||||||||||
| rsnumber | |||||||||||||
| Gene | NC | NS | NC | NS | No | Yes | No | Yes | Pint‡ | Ref | |||
| PTGS2 (COX-2) | rs689566 | A-1195G | AA-AG | 618 | 1169 | 16 | 19 | 1.00 | 1.01 (0.85–1.21) | 1.00 | 0.99 (0.83–1.19) | 19 | |
| GG | 31 | 43 | 274 | 529 | 1.23 (0.76–1.99) | 1.47 (0.63–3.44) | 1.27 (0.78–2.06) | 1.86 (0.89–3.88) | 0.39 | 19 | |||
| rs20417 | G-765C | GG | 477 | 874 | 218 | 391 | 1.00 | 1.09 (0.89–1.34) | 1.00 | 1.07 (0.87–1.32) | 19 | ||
| GC-CC | 165 | 330 | 68 | 152 | 0.96 (0.77–1.20) | 0.84 (0.61–1.15) | 0.93 (0.74–1.17) | 0.80 (0.58–1.10) | 0.18 | 19 | |||
| rs20417§ | G-765C | GG | 73 | 22 | |||||||||
| GC-CC | 27 | 0.67 | 22 | ||||||||||
| rs5275 | T8473C | TT | 292 | 514 | 134 | 215 | 1.00 (–) | 1.12 (0.86–1.46) | 1.00 (–) | 1.14 (0.87–1.49) | 19 | ||
| TC-CC | 346 | 695 | 151 | 326 | 0.88 (0.72–1.07) | 0.87 (0.68–1.11) | 0.87 (0.71–1.06) | 0.82 (0.64–1.06) | 0.21 | 19 | |||
| PPARG | rs3856806 | C1431T | CC | 191 | 376 | 85 | 173 | 1.00 (–) | 0.98 (0.71–1.35) | 1.00 (–) | 0.96 (0.70–1.33) | 20 | |
| CT-TT | 68 | 153 | 39 | 61 | 0.86 (0.61–1.21) | 1.26 (0.80–1.98) | 0.85 (0.60–1.21) | 1.22 (0.76–1.95) | 0.73 | 20 | |||
| rs1801282 | Pro12Ala | CC | 173 | 375 | 77 | 170 | 1.00 (–) | 1.02 (0.73–1.41) | 1.00 (–) | 1.01 (0.73–1.42) | 20 | ||
| CG and GG | 67 | 137 | 33 | 64 | 1.01 (0.71–1.43) | 1.30 (0.82–2.06) | 1.04 (0.72–1.48) | 1.29 (0.80–2.06) | 0.42 | 20 | |||
| IL10 | rs1800872 | C-592A | CC | 421 | 750 | 172 | 334 | 1.00 | 0.96 (0.76–1.20) | 1.00 | 0.97 (0.77–1.21) | 19 | |
| AC-AA | 230 | 460 | 118 | 217 | 0.89 (0.73–1.09) | 0.99 (0.76–1.29) | 0.91 (0.74–1.12) | 0.96 (0.73–1.25) | 0.58 | 19 | |||
| rs3024505 | CC | 432 | 840 | 210 | 366 | 1.00 | 1.14 (0.93–1.41) | 1.00 | 1.11 (0.90–1.38) | 19 | |||
| CT-TT | 214 | 384 | 81 | 188 | 1.07 (0.87–1.32) | 0.88 (0.66–1.18) | 1.08 (0.87–1.33) | 0.89 (0.66–1.19) | 0.05 | 19 | |||
| IL1B | rs4848306 | C-3737T | CC | 235 | 376 | 99 | 189 | 1.00 | 0.87 (0.65–1.18) | 1.00 | 0.82 (0.61–1.12) | 19 | |
| CT-TT | 409 | 834 | 190 | 361 | 0.76 (0.62–0.93) | 0.84 (0.66–1.08) | 0.74 (0.60–0.91) | 0.82 (0.64–1.06) | 0.04 | 19 | |||
| rs1143623 | G-1464C | GG | 322 | 652 | 129 | 279 | 1.00 | 0.99 (0.77–1.28) | 1.00 | 0.97 (0.75–1.25) | 19 | ||
| GC-CC | 326 | 561 | 161 | 270 | 1.19 (0.98–1.45) | 1.25 (0.98–1.59) | 1.20 (0.98–1.46) | 1.24 (0.97–1.58) | 0.65 | 19 | |||
| rs1143627 | T-31C | TT | 281 | 545 | 105 | 233 | 1.00 | 0.91 (0.69–1.20) | 1.00 | 0.90 (0.68–1.19) | 19 | ||
| TC-CC | 369 | 672 | 183 | 319 | 1.07 (0.88–1.30) | 1.16 (0.91–1.47) | 1.07 (0.88–1.31) | 1.13 (0.89–1.44) | 0.27 | 19 | |||
| HMOX | rs2071746 | A-413T | AA | 76 | 180 | 42 | 80 | 1.00 (–) | 1.20 (0.75–1.91) | 1.00 (–) | 1.14 (0.70–1.86) | 47 | |
| AT/TT | 183 | 349 | 82 | 154 | 1.22 (0.88–1.70) | 1.30 (0.88–1.92) | 1.20 (0.85–1.69) | 1.27 (0.85–1.88) | 0.73 | 47 | |||
| IL6 | rs1800795 | GG | 62 | 129 | 27 | 53 | 1.00 (–) | 1.27 (0.73–2.23) | 1.00 (–) | 1.23 (0.70–2.18) | 20 | ||
| G-174C | CG and CC | 178 | 383 | 83 | 181 | 1.04 (0.73–1.50) | 1.08 (0.72–1.62) | 1.04 (0.72–1.50) | 1.07 (0.70–1.62) | 0.48 | 20 | ||
| IL8 | rs4073 | T-251A | TT | 60 | 101 | 23 | 59 | 1.00 (–) | 0.77 (0.43–1.38) | 1.00 (–) | 0.74 (0.40–1.37) | 20 | |
| AT and AA | 180 | 411 | 87 | 175 | 0.80 (0.55–1.15) | 0.96 (0.63–1.45) | 0.81 (0.55–1.19) | 0.97 (0.63–1.49) | 0.08 | 20 | |||
| rs3856806 | C1431T | CC | 175 | 374 | 78 | 176 | 1.00 (–) | 0.98 (0.71–1.36) | 1.00 (–) | 0.99 (0.71–1.38) | 20 | ||
| CT and TT | 65 | 138 | 32 | 58 | 0.98 (0.69–1.39) | 1.37 (0.86–2.20) | 1.01 (0.71–1.45) | 1.35 (0.83–2.21) | 0.23 | 20 | |||
| ABCB1 (MDR1) | rs1045642 | 3435 | CC | 32 | 41 | 39 | 79 | 1.00 (–) | 2.21 (1.17–4.17) | 1.00 (–) | 2.34 (1.22–4.48) | 14 | |
| CT-TT | 82 | 204 | 198 | 449 | 0.92 (0.60–1.41) | 0.83 (0.52–1.33) | 0.99 (0.63–1.54) | 0.86 (0.53–1.39) | 0.001 | 14 | |||
| rs3789243 | in 3 | GG | 27 | 54 | 64 | 160 | 1.00 (–) | 1.35 (0.77–2.35) | 1.00 (–) | 1.31 (0.74–2.32) | 14 | ||
| GA-AA | 87 | 191 | 173 | 368 | 1.65 (1.15–2.38) | 1.65 (1.09–2.49) | 1.66 (1.15–2.41) | 1.61 (1.06–2.46) | 0.26 | 14 | |||
| ABCG2 (BCRP) | rs2231142 | 421 | CC | 97 | 199 | 178 | 414 | 1.00 (–) | 1.20 (0.88–1.63) | 1.00 (–) | 1.18 (0.85–1.62) | 14 | |
| CA-AA | 17 | 46 | 59 | 114 | 0.86 (0.58–1.27) | 0.62 (0.35–1.10) | 0.86 (0.57–1.29) | 0.60 (0.33–1.08) | 0.09 | 14 | |||
| ABCC2 (MRP2) | rs717620 | C-24T | CC | 167 | 350 | 93 | 158 | 1.00 | 1.26 (0.99–1.61) | 1.00 | 1.23 (0.96–1.58) | 18 | |
| CT and TT | 96 | 195 | 33 | 85 | 1.08 (0.85–1.39) | 0.85 (0.58–1.24) | 1.09 (0.85–1.41) | 0.85 (0.58–1.25) | 0.05 | 18 | |||
| rs2273697 | G1249A | GG | 162 | 331 | 76 | 149 | 1.00 | 1.10 (0.84–1.44) | 1.00 | 1.10 (0.84–1.44) | 18 | ||
| AG and AA | 101 | 214 | 50 | 94 | 0.98 (0.77–1.26) | 1.05 (0.77–1.44) | 0.99 (0.77–1.27) | 1.01 (0.74–1.38) | 0.75 | 18 | |||
| rs3740066 | C3972T | CC | 92 | 201 | 51 | 100 | 1.00 | 1.18 (0.84–1.64) | 1.00 | 1.13 (0.81–1.58) | 18 | ||
| CT and TT | 171 | 344 | 75 | 143 | 1.11 (0.87–1.43) | 1.15 (0.85–1.56) | 1.12 (0.88–1.44) | 1.16 (0.86–1.58) | 0.70 | 18 | |||
| SLC22A4 (OCTN) | C1672T | CC | 76 | 208 | 45 | 75 | 1.00 (–) | 1.62 (1.02–2.57) | 1.00 (–) | 1.60 (1.00–2.55) | 20 | ||
| CT and TT | 164 | 304 | 65 | 159 | 1.39 (1.00–1.93) | 1.20 (0.81–1.78) | 1.36 (0.97–1.91) | 1.16 (0.78–1.75) | 0.01 | 20 | |||
| SLC220A5 (OCTN) | G-209C | GG | 65 | 182 | 34 | 61 | 1.00 (–) | 1.49 (0.89–2.49) | 1.00 (–) | 1.44 (0.85–2.42) | 20 | ||
| GC and CC | 175 | 330 | 76 | 173 | 1.42 (1.01–2.00) | 1.34 (0.91–1.99) | 1.38 (0.97–1.95) | 1.30 (0.87–1.96) | 0.10 | 20 | |||
| (OCTN) | rs4705950 | CC | 81 | 210 | 42 | 74 | 1.00 (–) | 1.38 (0.86–2.19) | 1.00 (–) | 1.35 (0.84–2.16) | 20 | ||
| CT and TT | 159 | 302 | 68 | 160 | 1.25 (0.90–1.73) | 1.19 (0.81–1.74) | 1.22 (0.87–1.70) | 1.15 (0.77–1.71) | 0.13 | 20 | |||
| NOD2/CARD15 | rs20668441 | C2104T | CC | 226 | 479 | 101 | 221 | 1.00 (–) | 1.06 (0.80–1.41) | 1.00 (–) | 1.06 (0.79–1.42) | 20 | |
| CT | 14 | 33 | 9 | 13 | 0.93 (0.48–1.80) | 1.46 (0.60–3.55) | 1.01 (0.52–1.98) | 1.32 (0.53–3.25) | 0.55 | 20 | |||
| G2722C | GG | 236 | 496 | 109 | 233 | 1.00 (–) | 1.08 (0.82–1.42) | 1.00 (–) | 1.06 (0.80–1.41) | 20 | |||
| GC | 4 | 16 | 1 | 1 | 0.77 (0.29–2.05) | 1.15 (0.07–18.74) | 0.64 (0.23–1.76) | 1.49 (0.09–25.09) | 0.75 | 20 | |||
| 3020insC | 0 | 231 | 496 | 108 | 225 | 1.00 (–) | 1.11 (0.84–1.47) | 1.00 (–) | 1.10 (0.83–1.47) | 20 | |||
| 1 | 9 | 16 | 2 | 9 | 1.04 (0.45–2.42) | 0.68 (0.17–2.64) | 1.00 (0.41–2.48) | 0.52 (0.13–2.18) | 0.16 | 20 | |||
| DLG5 | G113A/R30Q | GG | 191 | 416 | 99 | 188 | 1.00 (–) | 1.22 (0.90–1.64) | 1.00 (–) | 1.21 (0.88–1.64) | 20 | ||
| AG/AA | 49 | 96 | 11 | 46 | 1.10 (0.74–1.62) | 0.62 (0.32–1.20) | 1.14 (0.76–1.71) | 0.63 (0.32–1.25) | 0.02 | 20 | |||
| NFKB1 | rs28362491 | -94ins/del | II | 84 | 211 | 38 | 96 | 1.00 (–) | 1.09 (0.69–1.73) | 1.00 (–) | 1.05 (0.66–1.67) | 15 | |
| ID-DD | 175 | 318 | 86 | 138 | 1.46 (1.06–2.02) | 1.60 (1.09–2.35) | 1.43 (1.02–2.00) | 1.56 (1.05–2.32) | 0.87 | 15 | |||
| NR1I2 (PXR) | rs1523127 | A-24381C | AA | 86 | 176 | 45 | 85 | 1.00 (–) | 1.10 (0.70–1.73) | 1.00 (–) | 1.11 (0.70–1.76) | 15 | |
| AC-CC | 173 | 353 | 79 | 149 | 0.98 (0.71–1.36) | 1.08 (0.74–1.59) | 1.00 (0.72–1.40) | 1.07 (0.72–1.58) | 0.85 | 15 | |||
| rs2276707 | C8055T | CC | 161 | 303 | 76 | 145 | 1.00 (–) | 1.04 (0.74–1.47) | 1.00 (–) | 1.00 (0.70–1.43) | 15 | ||
| CT-TT | 98 | 226 | 48 | 89 | 0.87 (0.64–1.19) | 1.04 (0.69–1.58) | 0.88 (0.64–1.20) | 1.06 (0.69–1.61) | 0.42 | 15 | |||
| rs6785049 | A7635G | AA | 91 | 184 | 46 | 80 | 1.00 (–) | 1.10 (0.70–1.72) | 1.00 (–) | 1.07 (0.67–1.70) | 15 | ||
| AG-GG | 168 | 345 | 78 | 154 | 0.97 (0.70–1.34) | 1.07 (0.73–1.57) | 0.95 (0.68–1.33) | 1.03 (0.69–1.54) | 0.96 | 15 | |||
| NR1H2 (LXR) | rs1405655 | CC | 121 | 239 | 53 | 109 | 1.00 (–) | 0.98 (0.65–1.46) | 1.00 (–) | 0.93 (0.61–1.41) | 15 | ||
| CT-TT | 138 | 290 | 71 | 125 | 0.90 (0.67–1.23) | 1.10 (0.75–1.60) | 0.89 (0.65–1.22) | 1.08 (0.74–1.58) | 0.24 | 15 | |||
| rs2695121 | TT | 85 | 166 | 32 | 61 | 1.00 (–) | 1.08 (0.65–1.80) | 1.00 (–) | 1.02 (0.59–1.75) | 15 | |||
| CT-CC | 174 | 363 | 92 | 173 | 0.91 (0.65–1.26) | 1.02 (0.70–1.47) | 0.89 (0.63–1.24) | 0.98 (0.67–1.44) | 0.72 | 15 | |||
| rs6983267¶ | rs6983267 | GG | 127 | 221 | 111 | 184 | 1.00 | 0.99 (0.71–1.38) | 1.00 | 0.99 (0.70–1.40) | 46 | ||
| GT | 250 | 339 | 155 | 411 | 1.00 | 0.60 (0.47–0.76) | 1.00 | 0.61 (0.47–0.79) | 46 | ||||
| TT | 104 | 201 | 60 | 207 | 1.00 | 0.55 (0.38–0.81) | 1.00 | 0.52 (0.35–0.78) | 0.01 | 46 | |||
Nc, number of cases; Ns, number of sub-cohort members.
Adjusted for sex and age.
In addition, adjusted for smoking status, alcohol, HRT status (women only), BMI, intake of red and processed meat, and dietary fibre.
P-value for interaction between the polymorphisms and NSAID use for the adjusted risk estimates (IRR†). IRR† indicates the slope of the line of the association between genotype and use of NSAID (“No” and “Yes”). The P-values in Table 1 indicate whether the slopes of the two lines are statistically significantly different.
This study was adjusted for age, gender, body mass index, C-reactive protein level, pack years of smoking, cholesterol, physical activity, total energy intake, rheumatoid arthritis, osteoarthritis and hormone replacement therapy.
This study was adjusted for age, race, sex, regular nonsterioidal anti-inflammatory drug use (yes or no), body mass index (in tertiles), physical activity (in tertiles), history of colorectal cancer in a parent or sibling (yes or no), smoking (never, former or current smoker), alcohol consumption (0–4.9 g, 5–9.9 g, 10–14.9 g or ≥15.0 g per day), post-menopausal hormone use (pre-menopausal, never, former or current user), consumption of beef, pork or lamb as a main dish (0–3 times per month, once a week, 2–4 times per week or ≥5 times per week), and energy-adjusted calcium and folate intake (in tertiles).
None of the studies was adjusted for multiple testing.