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. 2023 Feb 9;128(8):1529–1540. doi: 10.1038/s41416-023-02164-7

Table 3.

Hazard ratios and 95% confidence intervals for iron intake and the risk of colorectal cancer by anatomical subsites, EPIC cohort study, 1992–2014.

Quintiles of intakea Ptrend Continuous, per SD incrementb,c,d
Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5
Men
Total iron
Median intake (IQR), mg/day 9.3 (8.1; 10.2) 12.0 (11.5; 12.6) 14.1 (13.6; 14.6) 16.4 (15.8; 17.2) 20.5 (19.1; 23.0) Per 4.7 mg
Colon cancer
n cases 351 321 304 336 282 1594
HR (95%CI) 1.00 (Ref.) 0.91 (0.78, 1.06) 0.83 (0.70, 0.99) 0.92 (0.76, 1.11) 0.75 (0.60, 0.95) 0.059 0.95 (0.88, 1.03)
Proximal colon cancer
n cases 137 128 125 147 122 659
HR (95%CI) 1.00 (Ref.) 0.94 (0.73, 1.20) 0.91 (0.69, 1.19) 1.08 (0.81, 1.45) 0.92 (0.65, 1.31) 0.922 1.04 (0.92, 1.17)
Distal colon cancer
n cases 175 149 150 159 124 757
HR (95%CI) 1.00 (Ref.) 0.85 (0.68, 1.07) 0.82 (0.64, 1.05) 0.86 (0.66, 1.12) 0.63 (0.45, 0.88) 0.036 0.91 (0.81, 1.02)
Rectal cancer
n cases 215 224 206 214 198 1057
HR (95%CI) 1.00 (Ref.) 1.06 (0.87, 1.28) 0.95 (0.77, 1.18) 1.01 (0.80, 1.27) 0.94 (0.71, 1.25) 0.634 0.97 (0.88, 1.07)
Heme iron
Median intake (IQR), mg/day 0.51 (0.2; 0.7) 1.2 (1.0; 1.3) 1.7 (1.6; 1.8) 2.2 (2.1; 2.4) 3.2 (2.9; 3.9) Per 1.2 mg
Colon cancer
n cases 286 323 346 319 320 1594
HR (95%CI) 1.00 (Ref.) 1.03 (0.87, 1.21) 1.03 (0.87, 1.21) 0.98 (0.83, 1.16) 1.00 (0.83, 1.19) 0.783 1.03 (0.97, 1.09)
Proximal colon cancer
n cases 111 120 146 156 126
HR (95%CI) 1.00 (Ref.) 0.97 (0.74, 1.25) 1.09 (0.84, 1.40) 1.22 (0.94, 1.57) 1.00 (0.75, 1.33) 0.414 1.11 (1.02, 1.20)
Distal colon cancer
n cases 139 158 166 140 154 757
HR (95%CI) 1.00 (Ref.) 1.05 (0.83, 1.33) 1.04 (0.82, 1.31) 0.89 (0.70, 1.14) 0.99 (0.77, 1.29) 0.525 0.95 (0.88, 1.04)
Rectal cancer
n cases 169 209 231 218 230 1057
HR (95%CI) 1.00 (Ref.) 1.13 (0.92, 1.39) 1.20 (0.97, 1.47) 1.18 (0.95, 1.45) 1.29 (1.03, 1.61) 0.036 1.05 (0.98, 1.12)
Non-heme iron
Median intake (IQR), mg/day 8.1 (7.0; 8.8) 10.5 (10.0; 11.0) 12.4 (11.9; 12.8) 14.4 (13.9; 15.1) 18.1 (16.8; 20.2) Per 4.1 mg
Colon cancer
n cases 366 316 309 319 284 1594
HR (95%CI) 1.00 (Ref.) 0.86 (0.74, 1.01) 0.82 (0.69, 0.97) 0.84 (0.69, 1.01) 0.73 (0.58, 0.92) 0.018 0.94 (0.86, 1.01)
Proximal colon cancer
n cases 142 135 122 132 128 659
HR (95%CI) 1.00 (Ref.) 0.96 (0.75, 1.23) 0.86 (0.65, 1.12) 0.94 (0.70, 1.26) 0.94 (0.66, 1.33) 0.680 0.98 (0.87, 1.12)
Distal colon cancer
n cases 182 145 153 151 126 757
HR (95%CI) 1.00 (Ref.) 0.80 (0.64, 1.01) 0.81 (0.64, 1.04) 0.79 (0.60, 1.03) 0.62 (0.45, 0.87) 0.021 0.92 (0.82, 1.04)
Rectal cancer
n cases 218 226 214 203 196 1057
HR (95%CI) 1.00 (Ref.) 1.05 (0.86, 1.28) 0.98 (0.80, 1.22) 0.95 (0.75, 1.19) 0.93 (0.70, 1.23) 0.419 0.96 (0.87, 1.06)
Women
Total iron
Median intake (IQR), mg/day 7.8 (6.9; 8.5) 10.1 (9.6; 10.5) 11.8 (11.4; 12.2) 13.7 (13.2; 14.3) 17.1 (15.9; 19.0) Per 3.8 mg
Colon cancer
n cases 495 465 491 527 425 2403
HR (95%CI) 1.00 (Ref.) 0.97 (0.85, 1.11) 1.06 (0.92, 1.22) 1.19 (1.02, 1.39) 1.03 (0.85, 1.24) 0.138 1.02 (0.96, 1.09)
Proximal colon cancer
n cases 244 251 237 258 207 1197
HR (95%CI) 1.00 (Ref.) 1.05 (0.87, 1.26) 1.01 (0.83, 1.23) 1.13 (0.91, 1.41) 0.95 (0.73, 1.25) 0.878 1.01 (0.92, 1.10)
Distal colon cancer
n cases 209 169 210 214 167 969
HR (95%CI) 1.00 (Ref.) 0.85 (0.69, 1.05) 1.11 (0.90, 1.38) 1.20 (0.94, 1.52) 1.02 (0.76, 1.37) 0.166 1.05 (0.95, 1.16)
Rectal cancer
n cases 192 226 211 214 203 1046
HR (95%CI) 1.00 (Ref.) 1.14 (0.93, 1.38) 1.10 (0.89, 1.36) 1.13 (0.90, 1.42) 1.06 (0.80, 1.39) 0.710 1.02 (0.93, 1.12)
Heme iron
Median intake (IQR), mg/day 0.3 (0.1; 0.4) 0.75 (0.7; 0.8) 1.1 (1.0; 1.2) 1.5 (1.4; 1.6) 2.2 (2.0; 2.7) Per 0.8 mg
Colon cancer
n cases 446 479 506 498 474 2403
HR (95%CI) 1.00 (Ref.) 1.05 (0.93, 1.20) 1.02 (0.90, 1.17) 1.03 (0.90, 1.17) 0.99 (0.86, 1.14) 0.774 0.99 (0.94, 1.03)
Proximal colon cancer
n cases 232 242 249 245 229 1197
HR (95%CI) 1.00 (Ref.) 1.02 (0.85, 1.22) 0.94 (0.78, 1.13) 0.95 (0.78, 1.15) 0.89 (0.73, 1.09) 0.208 0.95 (0.89, 1.01)
Distal colon cancer
n cases 174 196 210 197 192 969
HR (95%CI) 1.00 (Ref.) 1.13 (0.92, 1.38) 1.14 (0.93, 1.40) 1.10 (0.89, 1.36) 1.10 (0.88, 1.39) 0.515 1.02 (0.95, 1.09)
Rectal cancer
n cases 202 194 209 233 208 1046
HR (95%CI) 1.00 (Ref.) 0.90 (0.74, 1.10) 0.89 (0.73, 1.08) 0.99 (0.81, 1.20) 0.87 (0.71, 1.07) 0.475 0.97 (0.91, 1.04)
Non-heme iron
Median intake (IQR), mg/day 7.0 (6.1; 7.6) 9.0 (8.6; 9.4) 10.6 (10.2; 11.0) 12.4 (11.9; 12.9) 15.4 (14.4; 17.1) Per 3.4 mg
Colon cancer
n cases 503 455 512 510 423 2403
HR (95%CI) 1.00 (Ref.) 0.95 (0.83, 1.08) 1.10 (0.96, 1.26) 1.14 (0.98, 1.33) 1.01 (0.83, 1.22) 0.226 1.03 (0.96, 1.10)
Proximal colon cancer
n cases 241 245 257 243 211 1197
HR (95%CI) 1.00 (Ref.) 1.06 (0.88, 1.28) 1.15 (0.94, 1.40) 1.12 (0.90, 1.40) 1.04 (0.79, 1.36) 0.591 1.03 (0.94, 1.13)
Distal colon cancer
n cases 213 170 207 214 165 969
HR (95%CI) 1.00 (Ref.) 0.84 (0.68, 1.04) 1.06 (0.86, 1.32) 1.16 (0.91, 1.47) 0.97 (0.72, 1.31) 0.308 1.05 (0.94, 1.16)
Rectal cancer
n cases 208 239 220 231 210 1108
HR (95%CI) 1.00 (Ref.) 1.17 (0.96, 1.42) 1.09 (0.88, 1.35) 1.16 (0.93, 1.46) 1.08 (0.82, 1.43) 0.627 1.04 (0.94, 1.14)

IQR interquartile range.

aThe analyses were run using country-specific quintiles.

bFor the continuous analysis, all the models were adjusted for the same variables as the in quintiles analysis, but with additional stratification by country.

cP values for heterogeneity by sex (using continuous values) for total iron, heme iron, and non-heme iron, respectively, were for all colon cancer, 0.994, 0.181, 0.573; proximal colon cancer 0.453, 0.004, 0.779; distal colon cancer, 0.505, 0.384, 0.665; rectal cancer, 0.691, 0.275, 0.352.

dIn men, P for heterogeneity colon vs. rectal cancer were 0.274, 0.814, 0.274 for total iron, heme iron, and non-heme iron, respectively; and P for heterogeneity proximal colon cancer vs. distal colon cancer were 0.129, 0.008, 0.448 for total iron, heme iron, and non-heme iron, respectively. In women, P for heterogeneity colon vs. rectal cancer were 0.999, 0.579, 0.999 for total iron, heme iron, and non-heme iron, respectively; and P for heterogeneity proximal colon cancer vs. distal colon cancer were 0.671, 0.162, 0.999 for total iron, heme iron, and non-heme iron, respectively.

There were 178 and 239 overlapping and non-specified colon or rectal cancer cases in men and women, respectively.

Models were adjusted for BMI, height, education, physical activity, smoking, energy intakes from alcohol, and total energy minus energy from alcohol, intakes of vitamin C, calcium, tea, coffee, and stratified by age at recruitment. In women specifically menopause status and hormone use were included in the model. For heme iron, additional confounders included intakes of cereal, and cereal products, legumes, and vegetables whereas for non-heme iron it included intakes of red meat, processed meats, poultry, and fish and fish products for non-heme iron.