Background
Methods
European Prospective Investigation into Cancer and Nutrition
Study participants
Intercept weight loss pilot intervention
Study participants
Laboratory analysis
Statistical analysis
Metabolic signatures of greater body sizes
Metabolic signatures of greater body sizes and cancer risk
Metabolic signatures of greater body size and weight loss
Results
European Prospective Investigation into Cancer and Nutrition | Intercept* | ||||||
---|---|---|---|---|---|---|---|
Discovery | Replication | Colorectal cancer | Endometrial cancer | ||||
Cases | Controls | Cases | Control | ||||
(n = 3029) | (n = 1297) | (n = 423) | (n = 423) | (n = 635) | (n = 648) | (n = 17) | |
Age, mean (SD) | 55.5 (8.1) | 55.8 (8.2) | 55.7 (7.8) | 55.8 (7.9) | 53.96 (7.9) | 53.99 (7.9) | 37.5 (9.7) |
Sex, n (%) | |||||||
Women | 964 (31.8) | 431 (33.2) | 257 (60.8) | 253 (59.9) | 635 (100) | 648 (100) | 11 (64.7) |
Educational level, n (%) | |||||||
University or higher | 674 (22.2) | 296 (22.8) | 62 (14.6) | 65 (15.3) | 116 (18.2) | 92 (14.2) | 13 (76.4) |
Body mass index (kg/m2), mean (SD) | 26.45 (3.7) | 26.47 (3.7) | 27.1 (4.5) | 26.51 (3.6) | 28 (5.4) | 25.85 (4.2) | 34.2 (3.8) |
Categories of BMI, n (%) | |||||||
Normal weight | 1101 (36.3) | 467 (36.0) | 142 (33.6) | 141 (33.3) | 210 (33.1) | 315 (48.6) | – |
Overweight | 1456 (48.1) | 619 (47.7) | 182 (43.0) | 216 (51.0) | 226 (35.6) | 239 (36.8) | 1 (5.8) |
Obese | 472 (15.6) | 211 (16.3) | 99 (23.4) | 66 (15.6) | 199 (31.3) | 94 (14.5) | 16 (94.2) |
Waist circumference (cm), mean (SD) | 90.7 (12.0) | 90.4 (12.1) | 89.6 (13.3) | 87.8 (11.5) | 85.7 (12.1) | 81.5 (10.5) | 102.8 (8.0) |
Waist-hip ratio (cm), mean (SD) | 0.89 (0.09) | 0.89 (0.09) | 0.87 (0.09) | 0.86 (0.1) | 0.81 (0.06) | 0.80 (0.06) | 0.86 (0.7) |
Height (cm), mean (SD) | 169.0 (8.8) | 168.9 (8.9) | 164.3 (9.1) | 163.8 (9.4) | 160.2 (6.6) | 160.2 (6.8) | 170.6 (7.9) |
Physical activity, n (%) | |||||||
Inactive | 679 (22.4) | 296 (22.8) | 133 (31.4) | 122 (28.8) | 95 (14.9) | 86 (13.3) | NA |
Moderately inactive | 1026 (33.9) | 463 (35.7) | 183 (43.2) | 175 (41.4) | 189 (29.7) | 175 (27.0) | NA |
Moderately active | 670 (22.1) | 278 (21.4) | 63 (14.9) | 71 (16.8) | 18 (2.8) | 13 (2.0) | NA |
Active | 597 (19.7) | 237 (18.3) | 44 (10.4) | 54 (12.7) | 115 (18.1) | 126 (19.4) | NA |
Smoking status, n (%) | |||||||
Never smoker | 1224 (40.4) | 518 (39.9) | 198 (46.8) | 222 (52.5) | 82 (12.9) | 111 (17.1) | NA |
Current smoker | 703 (23.2) | 299 (23.0) | 90 (21.3) | 77 (18.2) | 417 (65.6) | 396 (61.1) | NA |
Meat intake (g/d), mean (SD) | 86.5 (55.2) | 88.9 (59.5) | 76.7 (81.7) | 77.6 (44.4) | 634.7 (378.8) | 646.2 (376.4) | NA |
Fish intake (g/d), mean (SD) | 37.1 (37.2) | 35.3 (33.7) | 36.3 (32.4) | 37.9 (36.5) | 523.9 (316.5) | 509.0 (312.9) | NA |
Fibre intake (g/d), mean (SD) | 23.7 (8.1) | 23.3 (7.8) | 22.9 (7.6) | 23.3 (8.0) | NA | ||
Alcohol intake (g/d), mean (SD) | 3.1 (1.3) | 3.1 (1.27) | 2.9 (1.4) | 2.7 (1.3) | 3.1 (1.2) | 3.1 (1.2) | NA |
Energy intake (g/d), mean (SD) | 2253 (654.7) | 2255 (643.0) | 2221 (829.0) | 2187 (627.9) | 661 (383.9) | 667 (380.1) | NA |
Fasting status, n (%) | |||||||
Non-fasting | 1351 (44.6) | 601 (46.3) | 23 (5.4) | 23 (5.4) | 99 (15.6) | 105 (16.2) | 17 (100) |
Sub-study, n (%) | |||||||
Breast cancer controls | 752 (24.8) | 332 (25.6) | n/a | n/a | n/a | n/a | n/a |
Kidney cancer controls | 346 (11.4) | 134 (10.3) | n/a | n/a | n/a | n/a | n/a |
Hepatobiliary cancer controls | 151 (4.9) | 65 (5.0) | n/a | n/a | n/a | n/a | n/a |
Prostate cancer controls | 1780 (58.7) | 766 (59.0) | n/a | n/a | n/a | n/a | n/a |
Metabolic signatures of greater body sizes
N | Metabolites | Association with: | |||||
---|---|---|---|---|---|---|---|
BMI | WC | WHR | |||||
β (95% CI) | p* | β (95% CI) | p* | β (95% CI) | p* | ||
1 | Asparagine | − 1.02 (− 1.25; − 0.79) | < .001 | − 1.11 (− 1.38; − 0.84) | < .001 | − 0.80 (− 1.15; − 0.45) | < .001 |
2 | Glutamine | − 0.83 (− 1.05; − 0.60) | < .001 | − 0.92 (− 1.18; − 0.65) | < .001 | − 0.69 (− 1.03; − 0.35) | < .001 |
3 | Glutamate | 1.03 (0.83; 1.23) | < .001 | 1.08 (0.84; 1.32) | < .001 | 0.64 (0.33; 0.95) | < .001 |
4 | Glycine | − 1.01 (− 1.24; − 0.79) | < .001 | − 1.31 (− 1.57; − 1.04) | < .001 | − 1.40 (− 1.74; − 1.05) | < .001 |
5 | Isoleucine | 1.04 (0.80; 1.27) | < .001 | 1.24 (0.95; 1.52) | < .001 | 1.03 (0.66; 1.39) | < .001 |
6 | Serine | − 0.93 (− 1.15; − 0.71) | < .001 | − 1.02 (− 1.29; − 0.76) | < .001 | − 1.04 (− 1.38; − 0.69) | < .001 |
7 | Valine | 1.35 (1.12; 1.58) | < .001 | 1.49 (1.22; 1.77) | < .001 | 1.17 (0.82; 1.53) | < .001 |
8 | LysoPC a C17:0 | − 1.14 (− 1.35; − 0.92) | < .001 | − 1.31 (− 1.56; − 1.05) | < .001 | − 0.82 (− 1.15; − 0.48) | < .001 |
9 | LysoPC a C18:1 | −1.36 (− 1.57; − 1.16) | < .001 | − 1.51 (− 1.75; − 1.27) | < .001 | − 0.97 (− 1.28; − 0.65) | < .001 |
10 | LysoPC a C18:2 | − 1.47 (− 1.68; − 1.25) | < .001 | − 1.59 (− 1.85; − 1.33) | < .001 | − 1.00 (− 1.34; − 0.66) | < .001 |
11 | PC aa C38:3 | 1.69 (1.46; 1.92) | < .001 | 1.85 (1.57; 2.12) | < .001 | 1.62 (1.27; 1.98) | < .001 |
12 | PC aa C38:4 | 1.06 (0.83; 1.30) | < .001 | 1.26 (0.98; 1.54) | < .001 | 1.20 (0.84; 1.56) | < .001 |
13 | PC aa C42:0 | − 0.22 (− 0.27; − 0.17) | < .001 | − 0.26 (− 0.32; − 0.20) | < .001 | − 0.23 (− 0.31; − 0.15) | < .001 |
14 | PC ae C34:3 | − 1.26 (− 1.49; − 1.03) | < .001 | − 1.7 (− 1.97; − 1.42) | < .001 | − 1.77 (− 2.12; − 1.42) | < .001 |
15 | PC ae C40:5 | − 1.06 (− 1.29; − 0.83) | < .001 | − 1.24 (− 1.51; − 0.97) | < .001 | − 0.99 (− 1.34; − 0.64) | < .001 |
16 | PC ae C42:5 | − 1.13 (− 1.35; − 0.91) | < .001 | − 1.34 (− 1.6; − 1.08) | < .001 | − 1.14 (− 1.48; − 0.8) | < .001 |
17 | Acylcarnitine C0 | 0.85 (0.61; 1.09) | < .001 | 0.92 (0.64; 1.21) | < .001 | – | – |
18 | Acylcarnitine C3 | 0.27 (0.14; 0.41) | < .001 | 0.34 (0.18; 0.49) | < .001 | – | – |
19 | Acylcarnitine C5 | 0.69 (0.51; 0.86) | < .001 | 0.63 (0.42; 0.83) | < .001 | – | – |
20 | Leucine | 1.09 (0.85; 1.33) | < .001 | 1.23 (0.95; 1.52) | < .001 | – | – |
21 | Phenylalanine | 0.78 (0.55; 1.01) | < .001 | 0.88 (0.61; 1.15) | < .001 | – | – |
22 | Tyrosine | 1.23 (0.98; 1.47) | < .001 | 1.22 (0.92; 1.51) | < .001 | – | – |
23 | Kynurenine | 1.10 (0.87; 1.33) | < .001 | 0.96 (0.68; 1.23) | < .001 | – | – |
24 | PC aa C32:1 | 0.58 (0.36; 0.81) | < .001 | 0.46 (0.20; 0.73) | 0.001 | – | – |
25 | PC aa C34:4 | 0.57 (0.32; 0.81) | <. 001 | 0.44 (0.15; 0.73) | 0.004 | – | – |
26 | PC aa C38:0 | − 0.46 (− 0.68; − 0.24) | <. 001 | − 0.62 (− 0.88; − 0.36) | < .001 | – | – |
27 | PC aa C40:2 | − 0.11 (− 0.17; − 0.05) | < .001 | − 0.14 (− 0.21; − 0.08) | < .001 | – | – |
28 | PC aa C40:4 | 0.61 (0.36; 0.85) | < .001 | 0.78 (0.50; 1.07) | < .001 | – | – |
29 | PC aa C40:6 | 0.73 (0.49; 0.96) | < .001 | 0.76 (0.49; 1.04) | < .001 | – | – |
30 | PC aa C42:1 | − 0.12 (− 0.15; − 0.09) | < .001 | − 0.15 (− 0.18; − 0.11) | < .001 | – | – |
31 | PC aa C42:2 | − 0.56 (− 0.72; − 0.40) | < .001 | − 0.61 (− 0.80; − 0.42) | < .001 | – | – |
32 | PC ae C32:1 | − 0.57 (− 0.78; − 0.37) | < .001 | − 0.9 (− 1.14; − 0.66) | < .001 | – | – |
33 | PC ae C34:2 | − 0.92 (− 1.14; − 0.71) | < .001 | − 1.24 (− 1.49; − 0.98) | < .001 | – | – |
34 | PC ae C36:2 | − 1.12 (− 1.35; − 0.90) | < .001 | − 1.32 (− 1.59; − 1.05) | < .001 | – | – |
35 | PC ae C36:3 | −0.87 (− 1.10; − 0.65) | < .001 | − 1.15 (− 1.42; − 0.88) | < .001 | – | – |
36 | PC ae C38:2 | − 1.05 (− 1.27; − 0.82) | < .001 | − 1.19 (− 1.46; − 0.92) | < .001 | – | – |
37 | PC ae C40:6 | − 0.89 (− 1.12; − 0.65) | < .001 | − 1.11 (− 1.38; − 0.83) | < .001 | – | – |
38 | PC ae C44:4 | − 1.05 (− 1.24; − 0.86) | < .001 | − 1.11 (− 1.34; − 0.89) | < .001 | – | – |
39 | SM C16:0 | − 0.58 (− 0.74; − 0.42) | < .001 | − 0.64 (− 0.83; − 0.45) | < .001 | – | – |
40 | PC ae C44:6 | − 0.64 (− 0.87; − 0.42) | < .001 | – | – | – | – |
41 | SM C18:1 | 0.49 (0.34; 0.64) | < .001 | – | – | – | – |
42 | Hexoses | 0.65 (0.44; 0.87) | < .001 | – | – | – | – |
43 | PC aa C32:2 | – | – | 0.45 (0.19; 0.72) | 0.002 | – | – |