Background
Methods
Study population
Assessment of exposure, outcome, and covariates
Genotyping
Genetic instrument for serum CRP level
Statistical analysis
Results
Baseline characteristics
Overall (N=420,964) | No cancer (N=385,985) | Incident cancer (N=34,979) | |
---|---|---|---|
CRP at baseline,(mg/L) | 2.4 ± 3.3 | 2.4 ± 3.3 | 2.7 ± 3.6 |
Age at baseline,(years) | 56.2 ± 8.1 | 55.9 ± 8.1 | 60.2 ± 6.8 |
Male,n(%) | 197,223 (46.9) | 178,749 (46.3) | 18,474 (52.8) |
Ethnic,n(%) | |||
White | 395,650 (94.0) | 361,760 (93.7) | 33,890 (96.9) |
Asian | 9994 (2.4) | 9632 (2.5) | 362 (1.0) |
African | 6829 (1.6) | 6557 (1.7) | 272 (0.8) |
Mixed background | 2551 (0.6) | 2427 (0.6) | 124 (0.4) |
Unknown | 5940 (1.4) | 5609 (1.5) | 331 (0.9) |
Education,n(%) | |||
No degree | 278,328 (66.1) | 254,225 (65.9) | 24,103 (68.9) |
Degree | 137,610 (32.7) | 127,166 (33.0) | 10,444 (29.9) |
Unknown | 5026 (1.2) | 4594 (1.1) | 432 (1.2) |
Townsend deprivation index | −1.3 ± 3.1 | −1.3 ± 3.1 | −1.5 ± 3.0 |
Standing height, (cm) | 168.6 ± 9.3 | 168.6 ± 9.3 | 169.3 ± 9.1 |
BMI, (kg/m2) | 27.4 ± 4.8 | 27.4 ± 4.8 | 27.6 ± 4.7 |
Smoking status,n(%) | |||
Never | 230,940 (54.9) | 213,858 (55.4) | 17,082 (48.8) |
Previous | 143,521 (34.1) | 129,772 (33.6) | 13,749 (39.3) |
Current | 44,385 (10.5) | 40,431 (10.5) | 3954 (11.3) |
Unknown | 2118 (0.5) | 1924 (0.5) | 194 (0.6) |
Alcohol use,n(%) | |||
Never | 18,583 (4.4) | 17,311 (4.5) | 1272 (3.6) |
Previous | 14,892 (3.5) | 13,547 (3.5) | 1345 (3.9) |
Current | 386,411 (91.8) | 354,112 (91.7) | 32,299 (92.3) |
Unknown | 1078 (0.3) | 1015 (0.3) | 63 (0.2) |
Physical activity (MET/week),n(%) | |||
<600 | 63,447 (15.0) | 58,199 (15.1) | 5248 (15.0) |
600–3000 | 252,403 (60.0) | 231,494 (60.0) | 20,909 (59.8) |
≥3000 | 105,114 (25.0) | 96,292 (24.9) | 8822 (25.2) |
Having family cancer history,n(%) | 145,198 (34.5) | 131,509 (34.1) | 13,689 (39.1) |
Menopausal,n(%)a | |||
No | 55,655 (24.9) | 53,240 (25.7) | 2,415 (14.6) |
Yes | 133,190 (59.5) | 121,674 (58.7) | 11,516 (69.8) |
Not sure | 34,209 (15.3) | 31,665 (15.3) | 2544 (15.4) |
Unknown | 687 (0.3) | 657 (0.3) | 30 (0.2) |
Oral contraceptive use,n(%)a | |||
Never | 41,599 (18.6) | 38,025 (18.4) | 3574 (21.7) |
Ever | 181,103 (80.9) | 168,223 (81.2) | 12,880 (78.0) |
Unknown | 1039 (0.5) | 988 (0.5) | 51 (0.3) |
Hormone replacement therapy,n(%)a | |||
Never | 138,909 (62.1) | 130,148 (62.8) | 8761 (53.1) |
Ever | 83,657 (37.4) | 75,983 (36.7) | 7674 (46.5) |
Unknown | 1175 (0.5) | 1105 (0.5) | 70 (0.4) |
Assessment center,n(%) | |||
East Midlands | 28,471 (6.8) | 26,106 (6.8) | 2365 (6.8) |
London | 58,162 (13.8) | 54,306 (14.1) | 3856 (11.0) |
North Eastern England | 49,043 (11.7) | 44,883 (11.6) | 4160 (11.9) |
North West England | 88,420 (21.0) | 80,906 (21.0) | 7514 (21.5) |
Scotland | 55,745 (13.2) | 50,767 (13.2) | 4978 (14.2) |
South East England | 12,216 (2.9) | 10,874 (2.8) | 1342 (3.8) |
South west England | 36,372 (8.6) | 33,252 (8.6) | 3120 (8.9) |
Wales | 17,998 (4.3) | 16,483 (4.3) | 1515 (4.3) |
West Midlands England | 37,451 (8.9) | 34,445 (8.9) | 3006 (8.6) |
Yorkshire and the Humber | 37,086 (8.8) | 33,963 (8.8) | 3123 (8.9) |
Observational association evaluation
Low CRP (≤ 3mg/L) | High CRP (>3 mg/L) | FDR-adjusted Pheterogeneity | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
No (incident cases) | Person years | HR (95%CI) | P | No (incident cases) | Person years | HR (95%CI) | P | |||
Overall cancer | 327,031 (26,173) | 2,237,479 | 1.04 (1.03,1.06) | <0.001 | <0.001 | 93,933 (8,806) | 635,846 | 1.01 (1.01,1.01) | <0.001 | <0.001 |
Head & neck (C00–14) | 301,209 (351) | 2,137,461 | 1.08 (0.93,1.25) | 0.318 | 0.663 | 85,283 (156) | 603,797 | 1.02 (0.99,1.05) | 0.180 | 0.482 |
Esophagus (C15) | 301,201 (344) | 2,137,476 | 1.14 (0.99,1.32) | 0.078 | 0.434 | 85,273 (146) | 603,701 | 1.04 (1.01,1.07) | 0.014 | 0.217 |
Stomach (C16) | 301,087 (229) | 2,136,975 | 1.05 (0.87,1.26) | 0.614 | 0.873 | 85,232 (106) | 603,559 | 1.03 (0.99,1.07) | 0.154 | 0.833 |
Colorectal (C18–20) | 303,003 (2,145) | 2,144,527 | 1.11 (1.04,1.18) | 0.001 | 0.033 | 85,917 (791) | 605,899 | 1.02 (1.00,1.03) | 0.027 | 0.006 |
Liver (C22) | 301,037 (179) | 2,136,852 | 1.20 (0.98,1.47) | 0.080 | 0.235 | 85,230 (103) | 603,594 | 1.01 (0.97,1.05) | 0.788 | 0.096 |
Gallbladder (C23–24) | 300,952 (94) | 2,136,473 | 0.87 (0.65,1.17) | 0.351 | 0.873 | 85,172 (45) | 603,354 | 0.90 (0.82,0.99) | 0.035 | 0.808 |
Pancreas (C25) | 301,268 (410) | 2,137,813 | 1.14 (0.99,1.30) | 0.066 | 0.163 | 85,286 (159) | 603,798 | 0.99 (0.95,1.02) | 0.510 | 0.052 |
Lung (C33–34) | 301,995 (1,137) | 2,140,855 | 1.26 (1.16,1.36) | <0.001 | <0.001 | 85,882 (755) | 606,121 | 1.03 (1.02,1.05) | <0.001 | <0.001 |
Melanoma (C43) | 301,966 (1,111) | 2,140,358 | 0.98 (0.9,1.07) | 0.655 | 0.663 | 85,437 (310) | 604,460 | 1.01 (0.99,1.04) | 0.238 | 0.464 |
Non-melanotic skin (C44) | 309,450 (8,597) | 2,170,575 | 1.01 (0.97,1.04) | 0.729 | 0.945 | 87,430 (2,305) | 612,401 | 1.01 (1.00,1.02) | 0.128 | 0.945 |
Breast (C50) | 160,803 (3,644) | 1,130,896 | 1.07 (1.02,1.13) | 0.003 | 0.007 | 51,446 (1,371) | 361,233 | 0.99 (0.98,1.00) | 0.137 | 0.001 |
Uterus (C54-55) | 157,651 (491) | 1,119,136 | 1.13 (1.00,1.28) | 0.050 | 0.226 | 50,382 (306) | 357,326 | 1.01 (0.99,1.04) | 0.321 | 0.082 |
Ovary (C56) | 157,548 (388) | 1,118,715 | 1.12 (0.97,1.29) | 0.126 | 0.304 | 50,223 (147) | 356,717 | 1.00 (0.96,1.04) | 0.993 | 0.138 |
Prostate (C61) | 148,034 (4,337) | 1,035,523 | 0.99 (0.95,1.03) | 0.649 | 0.824 | 36,092 (1,043) | 250,894 | 1.00 (0.99,1.01) | 0.811 | 0.712 |
Kidney (C64) | 301,320 (463) | 2,137,990 | 1.13 (0.99,1.28) | 0.066 | 0.477 | 85,362 (235) | 604,047 | 1.05 (1.03,1.07) | <0.001 | 0.278 |
Bladder (C67) | 301,270 (412) | 2,137,591 | 1.05 (0.91,1.20) | 0.524 | 0.819 | 85,281 (154) | 603,785 | 1.01 (0.98,1.05) | 0.394 | 0.670 |
CNS (C70–72) | 301,185 (327) | 2,137,370 | 1.14 (0.98,1.33) | 0.092 | 0.154 | 85,232 (105) | 603,587 | 0.96 (0.92,1.01) | 0.113 | 0.037 |
Thyroid (C73) | 301,031 (173) | 2,136,726 | 1.07 (0.86,1.32) | 0.553 | 0.819 | 85,179 (52) | 603,385 | 1.01 (0.96,1.07) | 0.617 | 0.656 |
Non-Hodgkin lymphoma (C82–85, 96) | 301,634 (776) | 2,139,208 | 1.08 (0.98,1.20) | 0.123 | 0.477 | 85,447 (320) | 604,276 | 1.02 (1.00,1.05) | 0.040 | 0.282 |
Multiple myeloma (C90) | 301,172 (315) | 2,137,379 | 0.89 (0.76,1.05) | 0.182 | 0.625 | 85,211 (84) | 603,538 | 0.96 (0.91,1.02) | 0.178 | 0.398 |
CLL (C91) | 301,166 (308) | 2,137,248 | 0.83 (0.70,0.98) | 0.033 | 0.154 | 85,205 (78) | 603,491 | 1.00 (0.95,1.05) | 0.924 | 0.042 |
Low CRP (<1 mg/L) | Average CRP (1 to 3 mg/L) | High CRP (>3 mg/L) | FDR-adjusted Ptrend | ||||||
---|---|---|---|---|---|---|---|---|---|
No. (incident cases) | No. (incident cases) | HR (95%CI) | P | No (incident cases) | HR (95%CI) | P | |||
Overall cancer | 166,888 (12,380) | 160,143 (13,793) | 1.05 (1.02, 1.07) | 0.001 | <0.001 | 93,933 (8806) | 1.15 (1.12, 1.18) | <0.001 | <0.001 |
Head & neck (C00–14) | 154,674 (166) | 146,535 (185) | 1.06 (0.85, 1.31) | 0.617 | 0.006 | 85,283 (156) | 1.46 (1.15, 1.85) | 0.002 | 0.002 |
Esophagus (C15) | 154,643 (136) | 146,558 (208) | 1.20 (0.96, 1.49) | 0.115 | 0.064 | 85,273 (146) | 1.31 (1.01, 1.68) | 0.038 | 0.038 |
Stomach (C16) | 154,605 (97) | 146,482 (132) | 1.10 (0.84, 1.44) | 0.500 | 0.064 | 85,232 (106) | 1.38 (1.02, 1.87) | 0.034 | 0.035 |
Colorectal (C18–20) | 155,467 (959) | 147,536 (1186) | 1.11 (1.02, 1.21) | 0.019 | <0.001 | 85,917 (791) | 1.27 (1.14, 1.40) | <0.001 | <0.001 |
Liver (C22) | 154,584 (76) | 146,453 (103) | 1.10 (0.81, 1.50) | 0.523 | 0.003 | 85,230 (103) | 1.73 (1.25, 2.40) | 0.001 | 0.001 |
Gallbladder (C23–24) | 154,553 (45) | 146,399 (49) | 0.82 (0.54, 1.24) | 0.344 | 0.818 | 85,172 (45) | 1.06 (0.67, 1.68) | 0.805 | 0.818 |
Pancreas (C25) | 154,678 (170) | 146,590 (240) | 1.15 (0.94, 1.41) | 0.164 | 0.212 | 85,286 (159) | 1.18 (0.93, 1.50) | 0.162 | 0.154 |
Lung (C33–34) | 154,927 (419) | 147,068 (718) | 1.37 (1.21, 1.55) | <0.001 | <0.001 | 85,882 (755) | 2.08 (1.83, 2.36) | <0.001 | <0.001 |
Melanoma (C43) | 155,064 (559) | 146,902 (552) | 1.01 (0.89,1.14) | 0.936 | 0.792 | 85,437 (310) | 1.03 (0.89, 1.21) | 0.661 | 0.684 |
Non-melanotic skin (C44) | 158,800 (4294) | 150,650 (4,303) | 0.99 (0.95,1.04) | 0.743 | 0.818 | 87,430 (2305) | 0.99 (0.94, 1.05) | 0.814 | 0.785 |
Breast (C50) | 83,335 (1704) | 77,468 (1940) | 1.15 (1.08, 1.23) | <0.001 | <0.001 | 51,446 (1371) | 1.20 (1.11, 1.31) | <0.001 | <0.001 |
Uterus (C54–55) | 81,841 (210) | 75,810 (281) | 1.01 (0.84, 1.21) | 0.957 | 0.116 | 50,382 (306) | 1.20 (0.97, 1.47) | 0.087 | 0.074 |
Ovary (C56) | 81,804 (173) | 75,744 (215) | 1.27 (1.03, 1.56) | 0.028 | 0.024 | 50,223 (147) | 1.37 (1.07, 1.76) | 0.014 | 0.011 |
Prostate (C61) | 74,992 (2116) | 73,042 (2221) | 0.99 (0.93, 1.06) | 0.832 | 0.221 | 36,092 (1043) | 0.94 (0.87, 1.02) | 0.134 | 0.171 |
Kidney (C64) | 154,689 (181) | 146,631 (282) | 1.26 (1.04, 1.53) | 0.018 | <0.001 | 85,362 (235) | 1.64 (1.33, 2.03) | <0.001 | <0.001 |
Bladder (C67) | 154,689 (181) | 146,581 (231) | 1.01 (0.83, 1.23) | 0.929 | 0.562 | 85,281 (154) | 1.09 (0.87, 1.38) | 0.447 | 0.460 |
CNS (C70–72) | 154,662 (154) | 146,523 (173) | 1.11 (0.89, 1.40) | 0.346 | 0.185 | 85,232 (105) | 1.23 (0.94, 1.62) | 0.129 | 0.126 |
Thyroid (C73) | 154,590 (82) | 146,441 (91) | 1.09 (0.80, 1.49) | 0.596 | 0.818 | 85,179 (52) | 0.93 (0.63, 1.38) | 0.711 | 0.789 |
Non-Hodgkin lymphoma (C82–85, 96) | 154,862 (354) | 146,772 (422) | 1.14 (0.99, 1.32) | 0.078 | <0.001 | 85,447 (320) | 1.53 (1.30, 1.81) | <0.001 | <0.001 |
Multiple myeloma (C90) | 154,670 (163) | 146,502 (152) | 0.82 (0.65, 1.03) | 0.082 | 0.058 | 85,211 (84) | 0.74 (0.55, 0.98) | 0.039 | 0.029 |
CLL (C91) | 154,675 (167) | 146,491 (141) | 0.74 (0.58, 0.93) | 0.010 | 0.015 | 85,205 (78) | 0.69 (0.51, 0.92) | 0.012 | 0.006 |