Table 4.
Hazard ratios and 95% confidence intervals (CI) for heme iron and meat mutagen intake in the NIH-AARP Diet and Health Study 1
| Variable | Quintile of heme intake (mg/1,000 kcal) or daily meat mutagen intake (ng/1,000 kcal) | P trend3 | ||||
|---|---|---|---|---|---|---|
|
| ||||||
| 1 | 2 | 3 | 4 | 5 | ||
|
| ||||||
| Heme iron intake (mg/1,000 kcal) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 241/296,684 | 274/596,346 | 302/596,125 | 301/593,768 | 299/591,211 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.14 (0.96–1.35) | 1.28 (1.08–1.52) | 1.32 (1.11–1.56) | 1.38 (1.17–1.64) | <0.0001 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.07 (0.90–1.28) | 1.18 (0.99–1.40) | 1.17 (0.98–1.39) | 1.17 (0.97–1.41) | 0.08 |
| Men | ||||||
| Cases/person-years | 146/342,879 | 166/342,461 | 193/342,647 | 192/341,077 | 198/339,879 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.14 (0.91–1.43) | 1.36 (1.10–1.69) | 1.39 (1.12–1.73) | 1.52 (1.22–1.88) | <0.0001 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.06 (0.85–1.33) | 1.22 (0.98–1.53) | 1.21 (0.96–1.51) | 1.24 (0.98–1.57) | 0.07 |
| Women | ||||||
| Cases/person-years | 95/253,805 | 108/253,884 | 109/253,478 | 109/252,690 | 101/251,332 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.13 (0.86–1.49) | 1.16 (0.88–1.53) | 1.20 (0.91–1.58) | 1.18 (0.89–1.56) | 0.28 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.09 (0.83–1.44) | 1.10 (0.83–1.46) | 1.11 (0.84–1.48) | 1.06 (0.78–1.43) | 0.82 |
|
| ||||||
| Heme from red meat (mg/1,000 kcal) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 238/597,849 | 282/596,472 | 278/595,592 | 312/593,486 | 307/590,734 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.19 (1.00–1.41) | 1.20 (1.01–1.42) | 1.38 (1.16–1.63) | 1.43 (1.20–1.70) | <0.0001 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.12 (0.94–1.33) | 1.09 (0.91–1.30) | 1.21 (1.01–1.45) | 1.20 (0.99–1.44) | 0.04 |
| Men | ||||||
| Cases/person-years | 140/343,676 | 173/342,480 | 176/342,084 | 204/341,016 | 202/339,687 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.25 (1.00–1.56) | 1.30 (1.04–1.63) | 1.55 (1.25–1.92) | 1.62 (1.30–2.01) | <0.0001 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.16 (0.93–1.46) | 1.17 (0.93–1.47) | 1.34 (1.06–1.69) | 1.32 (1.04–1.69) | 0.02 |
| Women | ||||||
| Cases/person-years | 98/254,173 | 109/253,993 | 102/253,508 | 108/252,470 | 105/251,047 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.10 (0.84–1.45) | 1.04 (0.79–1.38) | 1.13 (0.86–1.49) | 1.16 (0.88–1.53) | 0.30 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.06 (0.80–1.39) | 0.97 (0.73–1.30) | 1.03 (0.77–1.38) | 1.02 (0.75–1.38) | 0.94 |
|
| ||||||
| Overall mutagenic activity (revertant colonies/1,000 kcal) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 258/595,113 | 297/593,480 | 290/593,917 | 281/594,746 | 291/596,878 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.18 (1.00–1.39) | 1.18 (1.00–1.40) | 1.18 (0.99–1.39) | 1.26 (1.06–1.49) | 0.03 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.11 (0.94–1.31) | 1.09 (0.92–1.29) | 1.07 (0.90–1.27) | 1.13 (0.95–1.34) | 0.28 |
| Men | ||||||
| Cases/person-years | 143/341,599 | 197/340,877 | 175/341,981 | 190/341,495 | 190/342,990 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.41 (1.13–1.75) | 1.28 (1.03–1.60) | 1.43 (1.15–1.77) | 1.47 (1.18–1.83) | 0.008 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.32 (1.06–1.64) | 1.17 (0.94–1.47) | 1.28 (1.03–1.60) | 1.30 (1.04–1.63) | 0.13 |
| Women | ||||||
| Cases/person-years | 115/253,513 | 100/252,603 | 115/251,937 | 91/253,251 | 101/253,887 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.89 (0.68–1.17) | 1.06 (0.82–1.37) | 0.86 (0.65–1.13) | 0.99 (0.75–1.29) | 0.98 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.85 (0.65–1.12) | 1.00 (0.76–1.30) | 0.80 (0.60–1.06) | 0.92 (0.70–1.21) | 0.71 |
|
| ||||||
| DiMeIQx** (ng/1,000 kcal) (quartiles) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 494/1,076,064 | 217/475,182 | 218/474,216 | 240/474,017 | 244/474,653 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.95 (0.81–1.12) | 0.98 (0.83–1.14) | 1.10 (0.95–1.29) | 1.16 (0.99–1.35) | 0.02 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.97 (0.82–1.13) | 0.96 (0.82–1.13) | 1.06 (0.91–1.24) | 1.09 (0.94–1.27) | 0.13 |
| Men | ||||||
| Cases/person-years | 306/602,034 | 134/277,205 | 132/276,672 | 158/276,640 | 165/276,392 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.93 (0.76–1.13) | 0.93 (0.75–1.12) | 1.14 (0.94–1.38) | 1.22 (1.01–1.48) | 0.007 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.94 (0.77–1.16) | 0.91 (0.74–1.12) | 1.09 (0.90–1.33) | 1.14 (0.95–1.38) | 0.07 |
| Women | ||||||
| Cases/person-years | 192/474,030 | 83/197,978 | 86/197,544 | 82/197,377 | 79/198,261 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.01 (0.78–1.30) | 1.06 (0.83–1.37) | 1.04 (0.81–1.35) | 1.04 (0.80–1.35) | 0.80 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.01 (0.78–1.31) | 1.05 (0.81–1.36) | 1.02 (0.78–1.32) | 1.00 (0.77–1.31) | 0.99 |
|
| ||||||
| MeIQx (ng/1,000 kcal) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 266/595,605 | 269/595,642 | 287/595,857 | 309/593,701 | 286/592,328 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.03 (0.87–1.22) | 1.11 (0.94–1.31) | 1.22 (1.04–1.44) | 1.16 (0.98–1.37) | 0.04 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.00 (0.84–1.18) | 1.04 (0.88–1.24) | 1.12 (0.95–1.32) | 1.02 (0.86–1.21) | 0.73 |
| Men | ||||||
| Cases/person-years | 162/342,183 | 162/343,158 | 181/342,592 | 205/341,273 | 185/339,735 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.02 (0.82–1.26) | 1.15 (0.93–1.42) | 1.32 (1.08–1.63) | 1.23 (1.00–1.52) | 0.03 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.98 (0.79–1.22) | 1.06 (0.86–1.32) | 1.19 (0.96–1.47) | 1.05 (0.84–1.31) | 0.54 |
| Women | ||||||
| Cases/person-years | 104/253,421 | 107/253,483 | 106/253,365 | 104/252,428 | 101/252,593 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.06 (0.81–1.38) | 1.06 (0.81–1.38) | 1.06 (0.81–1.39) | 1.05 (0.80–1.38) | 0.84 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.04 (0.79–1.36) | 1.02 (0.78–1.34) | 1.01 (0.76–1.33) | 0.97 (0.73–1.29) | 0.69 |
|
| ||||||
| PhIP (ng/1,000 kcal) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 282/592,538 | 286/594,293 | 289/594,297 | 268/595,216 | 292/597,790 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.03 (0.88–1.22) | 1.08 (0.91–1.27) | 1.02 (0.86–1.21) | 1.14 (0.97–1.35) | 0.10 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.99 (0.84–1.16) | 1.01 (0.85–1.19) | 0.95 (0.80–1.12) | 1.06 (0.89–1.25) | 0.39 |
| Men | ||||||
| Cases/person-years | 164/340,098 | 185/341,296 | 187/341,818 | 160/342,443 | 199/343,287 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 1.14 (0.93–1.41) | 1.19 (0.96–1.46) | 1.03 (0.83–1.29) | 1.32 (1.07–1.62) | 0.03 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 1.08 (0.87–1.34) | 1.10 (0.89–1.36) | 0.94 (0.76–1.18) | 1.20 (0.97–1.48) | 0.16 |
| Women | ||||||
| Cases/person-years | 118/252,440 | 101/252,996 | 102/252,479 | 108/252,772 | 93/254,504 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.88 (0.68–1.15) | 0.92 (0.71–1.20) | 1.01 (0.78–1.31) | 0.90 (0.68–1.18) | 0.72 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.85 (0.65–1.11) | 0.88 (0.67–1.15) | 0.95 (0.73–1.24) | 0.85 (0.64–1.12) | 0.52 |
|
| ||||||
| BaP (ng/1,000 kcal) | ||||||
| Men and women combined4 | ||||||
| Cases/person-years | 308/590,261 | 282/593,461 | 282/595,836 | 260/597,161 | 285/597,413 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.93 (0.79–1.09) | 0.94 (0.80–1.11) | 0.89 (0.76–1.05) | 1.04 (0.88–1.22) | 0.37 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.92 (0.78–1.08) | 0.95 (0.81–1.12) | 0.88 (0.74–1.04) | 0.98 (0.83–1.16) | 0.86 |
| Men | ||||||
| Cases/person-years | 199/338,320 | 178/341,441 | 172/342,464 | 162/343,290 | 184/343,427 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.90 (0.74–1.11) | 0.89 (0.72–1.09) | 0.85 (0.69–1.05) | 1.02 (0.83–1.25) | 0.46 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.90 (0.74–1.11) | 0.90 (0.73–1.11) | 0.84 (0.68–1.03) | 0.95 (0.78–1.17) | 0.94 |
| Women | ||||||
| Cases/person-years | 109/251,941 | 104/252,020 | 110/253,372 | 98/253,871 | 101/253,986 | |
| Age-adjusted HR (95% CI) | 1.00 (reference) | 0.98 (0.75–1.28) | 1.04 (0.80–1.36) | 0.97 (0.74–1.27) | 1.07 (0.81–1.40) | 0.27 |
| Multivariable HR (95% CI) 2 | 1.00 (reference) | 0.96 (0.73–1.25) | 1.05 (0.80–1.37) | 0.96 (0.73–1.26) | 1.04 (0.79–1.37) | 0.74 |
1
Cohort that successfully completed the meat module questions on the RFQ: n=322,846 subjects (1,417 cases), 187,265 men (895 cases), and 135,581 women (522 cases).
2
Cox proportional hazard models used to calculate hazard ratios. All nutrients are adjusted for energy by the density method with energy also in the model. Models are additionally adjusted for smoking (never, quit ≥10 y, quit 5 to 9 y ago, quit 1 to 4 y ago, quit <1 y ago or current and smoked ≤20 cigarettes/day, quit <1 y ago or current and smoked >20 cigarettes/day, and missing), BMI (kg/m2, <18.5, ≥18.5 and <25, ≥25 and <30, ≥30 and <35, ≥35, and missing), self-reported diabetes (yes, no), and energy-adjusted saturated fat (continuous). P value for interaction by sex: heme iron = 0.17, heme iron from red meat = 0.11, overall mutagenic activity = 0.15, DiMeIQx = 0.25, MeIQx = 0.32, PhIP = 0.12, BaP = 0.96
3
P trend calculated using median values for each quintile
4
Sex combined models additionally adjusted for sex.