Table 2.
Association of circulating insulin-like growth factor-1 with incident total and site-specific cancers1
| Quintile of insulin-like growth factor-1 | ||||||
|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | Q5 | Ptrend | |
| Total cancer,2 women (N = 11,137) | ||||||
| Cases/person-years | 2,471/278,733 | 2,335/283,919 | 2,212/284,491 | 2,123/285,907 | 1,996/286,424 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.99 (0.93, 1.05) | 0.99 (0.93, 1.04) | 1.00 (0.95, 1.06) | 1.04 (0.98, 1.10) | 0.23 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.01 (0.95, 1.07) | 1.02 (0.96, 1.08) | 1.04 (0.98, 1.10) | 1.08 (1.02, 1.15) | 0.008 |
| Total cancer,2 men (N = 12,854) | ||||||
| Cases/person-years | 3,037/256,324 | 2,728/259,529 | 2,494/260,084 | 2,382/259,730 | 2,213/259,557 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.99 (0.94, 1.04) | 0.99 (0.93, 1.04) | 1.00 (0.95, 1.06) | 1.05 (1.00, 1.11) | 0.09 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.00 (0.95, 1.06) | 1.01 (0.95, 1.06) | 1.03 (0.98, 1.09) | 1.08 (1.02, 1.15) | 0.005 |
| Breast cancer (N = 4,666) | ||||||
| Cases/person-years | 901/289,734 | 884/294,022 | 966/294,238 | 943/295,019 | 972/295,111 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 1.00 (0.91, 1.09) | 1.12 (1.02, 1.23) | 1.13 (1.03, 1.23) | 1.22 (1.11, 1.34) | <0.001 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.00 (0.91, 1.10) | 1.13 (1.03, 1.24) | 1.13 (1.03, 1.25) | 1.24 (1.12, 1.36) | <0.001 |
| Prostate cancer (N = 5,548) | ||||||
| Cases/person-years | 1,214/266,774 | 1,195/269,067 | 1,114 /269,306 | 1,034/269,280 | 991/268,868 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 1.10 (1.02, 1.19) | 1.13 (1.04, 1.23) | 1.13 (1.04, 1.23) | 1.24 (1.14, 1.35) | <0.001 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.08 (0.99, 1.17) | 1.10 (1.01, 1.19) | 1.10 (1.01, 1.19) | 1.20 (1.10, 1.30) | <0.001 |
| Colorectal cancer (N = 2,975) | ||||||
| Cases/person-years | 666/575,984 | 656/579,238 | 591/579,403 | 528/578508 | 534/577,838 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 1.08 (0.97, 1.20) | 1.05 (0.94, 1.17) | 1.02 (0.91, 1.14) | 1.17 (1.04, 1.31) | 0.04 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.10 (0.98, 1.22) | 1.08 (0.96, 1.21) | 1.05 (0.94, 1.18) | 1.21 (1.08, 1.36) | 0.007 |
| Non-melanoma skin cancer (N = 11,879) | ||||||
| Cases/person-years | 2,771/558,945 | 2,531/564,215 | 2,466/564,584 | 2,185/565,210 | 1,926/566,431 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.99 (0.94, 1.05) | 1.04 (0.99, 1.10) | 1.00 (0.94, 1.06) | 0.99 (0.94, 1.05) | 0.97 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.96 (0.91, 1.01) | 0.99 (0.94, 1.05) | 0.95 (0.89, 1.00) | 0.94 (0.88, 1.00) | 0.04 |
| Melanoma (N = 1,502) | ||||||
| Cases/person-years | 300/577,378 | 311/580,780 | 295/580,129 | 295/579,507 | 301/578,746 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 1.08 (0.92, 1.27) | 1.07 (0.91, 1.26) | 1.12 (0.96, 1.32) | 1.23 (1.05, 1.45) | 0.01 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.04 (0.89, 1.23) | 1.02 (0.87, 1.20) | 1.06 (0.90, 1.25) | 1.15 (0.98, 1.36) | 0.09 |
| Lung cancer (N = 1,996) | ||||||
| Cases/person-years | 591/579,270 | 468/582,831 | 354/582,747 | 323/581,875 | 260/581,183 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.89 (0.78, 1.00) | 0.74 (0.65, 0.84) | 0.74 (0.65, 0.85) | 0.70 (0.60, 0.81) | <0.0001 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.96 (0.85, 1.09) | 0.85 (0.74, 0.97) | 0.87 (0.76, 1.00) | 0.84 (0.72, 0.97) | 0.005 |
| Hematopoietic cancer (N = 2,310) | ||||||
| Cases/person-years | 563/576,726 | 490/580,507 | 426/580,368 | 425/579,320 | 406/578,671 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.95 (0.84, 1.07) | 0.89 (0.78, 1.00) | 0.95 (0.84, 1.08) | 1.02 (0.90, 1.16) | 0.90 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.95 (0.84, 1.07) | 0.89 (0.78, 1.01) | 0.95 (0.84, 1.08) | 1.01 (0.89, 1.16) | 0.98 |
| Uterine cancer (N = 777) | ||||||
| Cases/person-years | 205/304,209 | 181/305,150 | 145/305,097 | 134/304,859 | 112/304,914 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.94 (0.77, 1.15) | 0.81 (0.65, 1.00) | 0.80 (0.64, 0.99) | 0.76 (0.60, 0.96) | 0.006 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.05 (0.86, 1.29) | 0.93 (0.75, 1.16) | 0.95 (0.76, 1.18) | 0.93 (0.73, 1.18) | 0.38 |
| Kidney cancer (N = 691) | ||||||
| Cases/person-years | 156/579,720 | 137/582,969 | 131/582,658 | 139/581,614 | 128/580,641 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.95 (0.76, 1.20) | 0.98 (0.78, 1.24) | 1.12 (0.89, 1.42) | 1.17 (0.92, 1.48) | 0.11 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.02 (0.81, 1.28) | 1.08 (0.85, 1.36) | 1.24 (0.98, 1.56) | 1.29 (1.01, 1.64) | 0.02 |
| Urothelial cancer (N = 677) | ||||||
| Cases/person-years | 173/579,213 | 145/582,637 | 127/582,641 | 111/581,590 | 121/580,793 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.93 (0.75, 1.17) | 0.90 (0.72, 1.14) | 0.87 (0.68, 1.10) | 1.10 (0.87, 1.40) | 0.72 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.97 (0.78, 1.21) | 0.96 (0.76, 1.21) | 0.93 (0.73, 1.19) | 1.20 (0.95, 1.52) | 0.27 |
| Head and neck cancer (N = 665) | ||||||
| Cases/person-years | 182/578,861 | 139/582,650 | 132/582,308 | 109/581,417 | 103/580,855 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.79 (0.64, 0.99) | 0.78 (0.62, 0.98) | 0.67 (0.53, 0.85) | 0.68 (0.53, 0.87) | 0.001 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.87 (0.70, 1.09) | 0.90 (0.72, 1.13) | 0.80 (0.63, 1.02) | 0.85 (0.66, 1.08) | 0.12 |
| Ovarian cancer (N = 532) | ||||||
| Cases/person-years | 129/305,001 | 134/305,942 | 104/305,484 | 99/305,470 | 66/305,313 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 1.10 (0.86, 1.40) | 0.90 (0.69, 1.17) | 0.91 (0.70, 1.18) | 0.66 (0.48, 0.89) | 0.004 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.10 (0.86, 1.41) | 0.89 (0.69, 1.16) | 0.90 (0.69, 1.17) | 0.64 (0.47, 0.87) | 0.002 |
| Pancreatic cancer (N = 569) | ||||||
| Cases/person-years | 136/580,292 | 114/583,588 | 106/583,323 | 127/582,394 | 86/581,678 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.93 (0.73, 1.19) | 0.94 (0.73, 1.22) | 1.24 (0.97, 1.59) | 0.98 (0.75, 1.29) | 0.47 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.97 (0.75, 1.24) | 1.00 (0.77, 1.29) | 1.32 (1.04, 1.69) | 1.05 (0.80, 1.39) | 0.15 |
| Esophageal cancer (N = 496) | ||||||
| Cases/person-years | 154/580,003 | 96/583,426 | 82/583,216 | 91/582,242 | 73/581,465 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.69 (0.54, 0.89) | 0.65 (0.49, 0.85) | 0.78 (0.60, 1.02) | 0.73 (0.55, 0.97) | 0.03 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.75 (0.58, 0.97) | 0.72 (0.55, 0.95) | 0.90 (0.69, 1.17) | 0.84 (0.63, 1.12) | 0.29 |
| Central nervous system cancer (N = 436) | ||||||
| Cases/person-years | 96/580,257 | 81/583,560 | 87/583,267 | 88/582,381 | 84/581,507 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.90 (0.67, 1.21) | 1.02 (0.76, 1.37) | 1.10 (0.82, 1.47) | 1.16 (0.86, 1.56) | 0.17 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.88 (0.66, 1.19) | 1.00 (0.75, 1.34) | 1.07 (0.80, 1.44) | 1.13 (0.83, 1.53) | 0.24 |
| Gastric cancer (N = 334) | ||||||
| Cases/person-years | 87/580,067 | 73/583,384 | 72/583,273 | 55/582,303 | 47/581,637 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.92 (0.68, 1.26) | 0.98 (0.72, 1.35) | 0.81 (0.58, 1.14) | 0.78 (0.54, 1.12) | 0.14 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.99 (0.72, 1.35) | 1.08 (0.79, 1.48) | 0.90 (0.64, 1.27) | 0.86 (0.60, 1.24) | 0.42 |
| Liver cancer (N = 238) | ||||||
| Cases/person-years | 123/580,259 | 47/583,635 | 24/583,448 | 27/582,497 | 17/581,694 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.41 (0.29, 0.58) | 0.22 (0.14, 0.35) | 0.27 (0.18, 0.41) | 0.19 (0.11, 0.32) | <0.001 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.44 (0.32, 0.62) | 0.25 (0.16, 0.38) | 0.30 (0.20, 0.46) | 0.21 (0.13, 0.36) | <0.001 |
| Mesothelioma (N = 240) | ||||||
| Cases/person-years | 58/580,351 | 46/583,669 | 48/583,415 | 48/582,477 | 40/581,709 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.91 (0.62, 1.34) | 1.07 (0.73, 1.57) | 1.20 (0.81, 1.76) | 1.18 (0.79, 1.77) | 0.23 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 0.91 (0.62, 1.34) | 1.08 (0.73, 1.59) | 1.21 (0.82, 1.77) | 1.18 (0.78, 1.78) | 0.23 |
| Thyroid cancer (N = 231) | ||||||
| Cases/person-years | 38/579,913 | 37/583,230 | 45/582,945 | 59/582,025 | 52/581,146 | |
| Model 1, HR (95% CI) | 1.00 (ref.) | 0.99 (0.63, 1.56) | 1.22 (0.79, 1.88) | 1.63 (1.08, 2.46) | 1.48 (0.96, 2.27) | 0.01 |
| Model 2, HR (95% CI) | 1.00 (ref.) | 1.00 (0.64, 1.58) | 1.24 (0.80, 1.92) | 1.66 (1.09, 2.51) | 1.50 (0.97, 2.32) | 0.01 |
Notes:
[1]
Model 1 adjusted for age (5-year categories), assessment center, and the first two principal components (as a proxy for genetic ancestry). Model 2 additionally adjusted for alcohol consumption (never, special occasions only, 1–3 times per month, 1–2 times per week, 3–4 times per week, daily/almost daily), smoking status (never, former, current), physical activity on the IPAQ scale (low, moderate, high, missing), height in cm (women: <155, 155–159, 160–164, 165–169, ≥170; men: <165, 165–169, 170–174, 175–179, ≥180), BMI in kg/m2 (<21, 21–24.9, 25–29.9, 30–34.9, ≥35), waist-to-hip ratio (women: ≤0.80, 0.81–0.85, >0.85; men: ≤0.90, 0.91–0.95, >0.95), average household income (less than £18,000, £18,000 to £30,999, £31,000 to £51,999, £52,000 to £100,000, greater than £100,000, refused, do not know). For female-specific cancers, we additionally adjusted for menopausal status (premenopausal, postmenopausal, unknown menopausal status), age at menarche (<12, 12–13, ≥14, missing), parity (nulliparous, 1, 2, 3, ≥4), age at first live birth (nulliparous, <20, 20–24, 25–29, ≥30), had prior breast cancer screening/mammograms (ever, never), ever used oral contraceptives (yes, no), ever used hormone replacement therapy (yes, no). For breast, prostate, colorectal, and lung cancer, we additionally adjusted for family history of the respective cancer in a first-degree relative.
[2]
Total cancer excludes non-melanoma skin cancer.