Table IV.
Association between iron intake and advanced colorectal adenoma and colorectal cancer risk stratified by genotypes possessing iron–SNP interactions P ≤ 0.10
| Gene | SNP | Genotype | Q1 | Q2 | Q3 | Q4 | P trend c | P trend b,c | P interaction c | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases/ controls | REF | Cases/ controls | OR (95% CI)a | OR (95% CI)b | Cases/ controls | OR(95% CI)a | OR (95% CI)b | Cases/ controls | OR(95% CI)a | OR (95% CI)b | ||||||
| Advanced colorectal adenoma | ||||||||||||||||
| Dietary iron | ||||||||||||||||
| HEPHL1 | rs7946162 | AA | 108/111 | 1.00 | 120/103 | 1.20 (0.82, 1.74) | 1.44 (0.94, 2.19) | 86/111 | 0.80 (0.54, 1.18) | 1.19 (0.73, 1.94) | 113/110 | 1.06 (0.72, 1.55) | 2.22 (1.15, 4.27) | 0.87 | 0.03 | 0.10 |
| AG+GG | 227/214 | 1.00 | 199/235 | 0.78 (0.60, 1.02) | 0.88 (0.66, 1.18) | 169/245 | 0.63 (0.48, 0.83) | 0.81 (0.57, 1.15) | 166/228 | 0.64 (0.48, 0.85) | 0.98 (0.62, 1.55) | 0.002 | 0.93 | |||
| HEPHL1 | rs2460063 | TT | 111/124 | 1.00 | 129/114 | 1.27 (0.89, 0.82) | 1.51 (1.01, 2.26) | 90/118 | 0.85 (0.58, 1.25) | 1.26 (0.78, 2.03) | 116/113 | 1.15 (0.79, 1.68) | 2.39 (1.26, 4.54) | 0.82 | 0.02 | 0.04 |
| TC+CC | 225/211 | 1.00 | 197/230 | 0.79 (0.60, 1.03) | 0.89 (0.66, 1.19) | 169/244 | 0.63 (0.48, 0.83) | 0.15 (0.57, 1.15) | 163/229 | 0.63 (0.47, 0.84) | 0.95 ( 0.60, 1.50) | 0.001 | 0.94 | |||
| HEPHL1 | rs7127348 | GG | 105/108 | 1.00 | 113/105 | 1.11 (0.76, 1.63) | 1.37 (0.90, 2.10) | 83/108 | 0.79 (0.53, 1.18) | 1.26 (0.76, 2.07) | 109/108 | 1.05 (0.71, 1.57) | 2.40 (1.23, 4.67) | 0.96 | 0.02 | 0.09 |
| GA+GG | 232/228 | 1.00 | 214/239 | 0.86 (0.66, 1.12) | 0.97 (0.73, 1.29) | 176/255 | 0.66 (0.50, 0.86) | 0.83 (0.59, 1.17) | 173/237 | 0.68 (0.51, 0.90) | 0.83 (0.64, 1.58) | 0.03 | 0.95 | |||
| TFR2 | rs4729598 | CC | 269/283 | 1.00 | 255/277 | 0.95 (0.75, 1.21) | 1.05 (0.81, 1.37) | 199/289 | 0.70 (0.54, 0.89) | 0 .91 (0.66, 1.24) | 221/255 | 0.86 (0.66, 1.10) | 1.31 (0.86, 1.98) | 0.11 | 0.21 | 0.07 |
| CT+TT | 68/53 | 1.00 | 72/68 | 0.84 (0.51, 1.37) | 1.08 (0.62, 1.89) | 60/74 | 0.68 (0.41, 1.13) | 1.09 (0.57, 2.08) | 61/88 | 0.58 (0.35, 0.96) | 1.37 (0.59, 3.20) | 0.03 | 0.45 | |||
| Heme iron | ||||||||||||||||
| ACO1 | rs1041320 | AA | 262/338 | 1.00 | 286/328 | 1.12 (0.89, 1.41) | 1.05 (0.83, 1.34) | 312/331 | 1.30 (1.03, 1.64) | 1.20 (0.93, 1.54) | 328/358 | 1.24 (0.98, 1.57) | 1.14 ( 0.85, 1.54) | 0.10 | 0.42 | 0.03 |
| AC+CC | 4/14 | 1.00 | 4/9 | 2.21 (0.34, 14.5) | 7.25 (0.30, 175.87) | 4/7 | 3.67 ( 0.50, 14.52) | 82.20 (0.60, 2492.20) | 5/2 | 19.27 (1.66, 223.07) | 118440.40 (29.66, 4.73e+08) | 0.02 | 0.004 | |||
| CYBRD1 | rs16859443 | GG | 243/332 | 1.00 | 274/324 | 1.15 (0.91, 1.46) | 1.09 (0.86, 1.40) | 302/327 | 1.35 (1.07, 1.71) | 1.25 (0.97, 1.62) | 324/345 | 1.36 (1.07, 1.73) | 1.26 (0.93, 1.70) | 0.02 | 0.16 | 0.08 |
| GA+AA | 23/20 | 1.00 | 15/13 | 0.80 (0.29, 2.22) | 0.66 (0.20, 2.19) | 14/11 | 0.98 ( 0.33, 2.86) | 0.49 (0.20, 2.19) | 9/15 | 0.36 (0.11, 1.19) | 0.26 (0.04, 1.56) | 0.10 | 0.15 | |||
| HFE | rs1799945 | CC | 203/277 | 1.00 | 214/266 | 1.06 (0.82. 1.23) | 1.01 (0.77, 1.32) | 228/262 | 1.25 (0.96, 1.63) | 1.17 (0.88, 1.56) | 248/258 | 1.33 (1.02, 1.76) | 1.33 (0.95, 1.86) | 0.03 | 0.07 | 0.09 |
| CG+GG | 63/75 | 1.00 | 76/71 | 1.36 (0.85, 2.19) | 1.30 (0.80, 2.13) | 88/76 | 1.53 (0.95, 2.45) | 1.36 (0.81, 2.28) | 85/102 | 1.13 (0.70, 1.84) | 0.80 (0.43, 1.48) | 0.93 | 0.19 | |||
| IREB2 | rs7183034 | CC | 72/125 | 1.00 | 78/90 | 1.46 (0.95, 2.24) | 1.41 (0.90, 2.21) | 95/101 | 1.75 (1.16, 2.65) | 1.58 (1.01, 2.47) | 98/94 | 1.86 (1.22, 2.86) | 1.55 (0.90, 2.66) | 0.009 | 0.200 | 0.03 |
| CT+TT | 193/227 | 1.00 | 212/247 | 1.01 (0.77, 1.32) | 0.95 (0.72, 1.26) | 220/236 | 1.16 (0.88, 1.53) | 1.10 (0.81, 1.48) | 235/266 | 1.09 (0.82, 1.45) | 1.06 (0.74, 1.51) | 0.52 | 0.66 | |||
| Colorectal cancer | ||||||||||||||||
| Total iron | ||||||||||||||||
| IGFBP3 | rs2453839 | TT | 66/77 | 1.00 | 57/52 | 1.34 (0.81, 2.22) | 1.53 (0.87, 2.68) | 57/58 | 1.14 (0.70, 1.87) | 1.24 (0.72, 2.12) | 51/46 | 1.29 (0.76, 2.17) | 1.62 (0.86, 3.05) | 0.47 | 0.28 | 0.08 |
| TC+CC | 41/40 | 1.00 | 36/28 | 1.24 (0.63, 2.42) | 1.13 (0.53, 2.41) | 27/53 | 0.47 (0.24, 0.90) | 0.42 (0.21, 0.83) | 35/46 | 0.68 (0.36, 1.29) | 0.62 (0.28, 1.35) | 0.05 | 0.03 | |||
| Dietary iron | ||||||||||||||||
| CYBRD1 | rs12052537 | CC | 49/64 | 1.00 | 62/74 | 0.98 (0.60, 1.61) | 1.18 (0.67, 2.08) | 48/71 | 1.54 (0.91, 2.59) | 2.17 (1.10, 4.29) | 65/45 | 1.14 (0.67. 1.93) | 2.00 (0.80, 5.04) | 0.43 | 0.10 | 0.04 |
| CA+AA | 37/30 | 1.00 | 40/38 | 1.41 (0.70, 2.83) | 1.46 (0.69, 3.12) | 36/35 | 0.75 (0.37, 1.50) | 0.64 (0.28, 1.47) | 28/34 | 0.74 (0.37, 1.49) | 0.53 (0.19, 1.50) | 0.19 | 0.12 | |||
| FTL | rs8104760 | TT | 79/87 | 1.00 | 96/109 | 1.24 (0.83, 1.86) | 1.26 (0.81, 1.97) | 76/97 | 1.14 (0.75, 1.75) | 1.14 (0.67, 1.93) | 84/76 | 0.94 (0.61, 1.45) | 0.92 (0.46, 1.84) | 0.63 | 0.66 | 0.06 |
| TG+GG | 8/8 | 1.00 | 8/6 | 1.17 (0.23, 5.99) | 1.49 (0.19, 11.84) | 9/11 | 2.69 (0.53, 13.74) | 6.77 (0.72, 63.93) | 10/17 | 2.34 (0.48, 11.42) | 11.81 ( 0.61, 228.94) | 0.21 | 0.06 | |||
| HAMP | rs916145 | GG | 67/76 | 1.00 | 79/88 | 1.31 (0.84, 20.4) | 1.51 (0.92, 2.47) | 60/94 | 1.50 (0.95, 2.38) | 1.85 (1.03, 3.31) | 67/65 | 1.25 (0.77, 2.03) | 1.74 (0.81, 3.77) | 0.36 | 0.20 | 0.10 |
| GC+CC | 20/19 | 1.00 | 25/27 | 1.02 (0.42, 2.45) | 0.77 (0.29, 2.06) | 25/14 | 0.75 (0.37, 1.50) | 0.38 (0.13, 1.17) | 27/18 | 0.74 (0.37, 1.49) | 0.26 (0.07, 1.05) | 0.06 | 0.04 | |||
| TFRC | rs7645812 | CC | 74/83 | 1.00 | 87/99 | 1.27 (0.83, 0.95) | 1.38 (0.86, 2.19) | 74/93 | 1.35 (0.86, 2.11) | 1.55 (0.90, 2.68) | 85/71 | 1.28 (0.82, 2.01) | 1.57 (0.77, 3.19) | 0.34 | 0.27 | 0.02 |
| CT+TT | 13/12 | 1.00 | 17/16 | 1.37 (0.48, 3.96) | 1.58 (0.43, 5.78) | 11/15 | 0.65 (0.22, 1.994) | 0.70 (0.17, 2.88) | 9/12 | 0.22 (0.06, 0.79) | 0.30 (0.04, 2.23) | 0.02 | 0.16 | |||
| Heme iron | ||||||||||||||||
| ACO1 | rs10970985 | GG | 27/44 | 1.00 | 43/50 | 1.32 (0.70, 2.50) | 1.51 (0.75, 3.02) | 42/43 | 1.84 (0.96, 3.56) | 2.50 (1.21, 5.13) | 50/40 | 2.45 (1.23, 4.85) | 3.40 (1.43, 8.06) | 0.009 | 0.004 | 0.05 |
| GC+CC | 60/51 | 1.00 | 60/63 | 0.82 (0.49, 1.40) | 0.74 (0.42, 1.29) | 43/64 | 0.56 (0.32, 0.97) | 0.50 (0.27, 0 .92) | 43/42 | 0.85 (0.45, 1.58) | 0.56 (0.25, 1.25) | 0.58 | 0.15 | |||
| HMOX1 | rs737777 | GG | 81/84 | 1.00 | 88/93 | 0.95(0.62, 1.46) | 0.94 (0.60, 1.47) | 73/88 | 0.92 (0.59, 1.43) | 0.97 (0.60, 1.56) | 74/71 | 1.17 (0.72, 1.90) | 1.08 (0.59, 1.96) | 0.46 | 0.74 | 0.10 |
| GT+TT | 5/11 | 1.00 | 16/22 | 1.85 (0.53, 6.57) | 2.66 (0.60, 11.85) | 12/20 | 1.41 (0.38, 5.20) | 2.29 (0.49, 10.59) | 19/12 | 4.39 (1.09, 17.65) | 14.91 (2.13, 104.69) | 0.03 | 0.008 | |||
aAssuming a dominant model, adjusted for age, race and ethnicity.
bAssuming a dominant model, adjusted for age, race, ethnicity, education, body mass index, cigarette smoking, use of aspirin and ibuprofen, physical activity, study center, total calories, dietary fiber, dietary calcium, alcohol and family history of colorectal cancer.
cNo associations were significant after adjustment for multiple comparison testing.