Table 1.
Characteristics and main findings of meta-analyses of observational studies reporting unique cancer and cardiovascular outcomes (direction of comparison is high versus low)
| Outcome | Biomarker | Meta-analysis metric | No of studies in each MA | No of events | Total No | Relative risk (95% CI)* | P value | I2 (95% CI) | Egger test P value |
|---|---|---|---|---|---|---|---|---|---|
| Cancer outcomes | |||||||||
| Aggressive prostate cancer | 25OHD | OR | 6 | 871 | 4524 | 0.98 (0.84 to 1.15) | 0.81 | 33 (0 to 73) | 0.97 |
| Aggressive prostate cancer | 1,25(OH)2D | OR | 2 | 696 | 1488 | 0.75 (0.48 to 1.17) | 0.21 | 0 (NA) | NA |
| Breast cancer | 25OHD | OR | 21 | 11 771 | 26 317 | 0.55 (0.42 to 0.71) | 1.0×10−5 | 88 (83 to 91) | 0.06 |
| Breast cancer | 1,25(OH)2D | OR | 3 | 1802 | 3627 | 0.99 (0.68 to 1.44) | 0.96 | 47 (0 to 84) | 0.86 |
| Breast cancer: postmenopausal | 25OHD | RR | 9 | 3929 | 8766 | 0.99 (0.97 to 1.01) | 0.33 | 0 (0 to 54) | 0.92 |
| Breast cancer: premenopausal | 25OHD | RR | 6 | 1613 | 2890 | 1.01 (0.97 to 1.06) | 0.67 | 37 (0 to 74) | 0.76 |
| Colon cancer | 25OHD | OR | 10 | 1822 | 4578 | 0.78 (0.56 to 1.07) | 0.13 | 50 (0 to 74) | 0.15 |
| Colon cancer | 1,25(OH)2D | OR | 4 | No info | No info | 0.88 (0.57 to 1.35) | 0.57 | NA | NA |
| Colorectal cancer | 25OHD | RR | 10 | 2764 | 6712 | 0.70 (0.58 to 0.84) | 0.0002 | 0 (0 to 53) | 0.40 |
| Colorectal cancer | 1,25(OH)2D | OR | 4 | No info | No info | 1.01 (0.59 to 1.73) | 0.97 | NA | NA |
| Kidney cancer | 25OHD | OR | 6 | 740 | 1480 | 1.01 (0.65 to 1.58) | 0.97 | 0 (0 to 61) | 0.37 |
| Non-Hodgkin’s lymphoma (females) | 25OHD | OR | 4 | 18 | 39 | 0.81 (0.39 to 1.70) | 0.59 | 0 (0 to 68) | 0.56 |
| Non-Hodgkin’s lymphoma (males) | 25OHD | OR | 6 | 25 | 65 | 0.65 (0.35 to 1.23) | 0.18 | 13 (0 to 66) | 0.72 |
| Ovarian cancer | 25OHD | OR | 10 | 884 | 2489 | 0.83 (0.63 to 1.09) | 0.18 | 0 (0 to 53) | 0.31 |
| Pancreatic cancer | 25OHD | OR | 6 | 866 | 2113 | 2.13 (1.02 to 4.47) | 0.04 | 17 (0 to 67) | 0.90 |
| Prostate cancer | 1,25(OH)2D | OR | 7 | 1361 | 3640 | 0.99 (0.87 to 1.14) | 0.89 | 40 (0 to 74) | 0.43 |
| Prostate cancer | 25OHD | OR | 14 | 4353 | 28 988 | 1.04 (0.98 to 1.09) | 0.15 | 0 (0 to 47) | 0.79 |
| Rectal cancer | 25OHD | OR | 9 | 868 | 2050 | 0.50 (0.29 to 0.88) | 0.01 | 51 (0 to 75) | 0.10 |
| Sporadic colorectal adenoma | 25OHD | OR | 9 | 2923 | 6268 | 0.82 (0.69 to 0.97) | 0.02 | 66 (13 to 82) | 0.34 |
| Sporadic colorectal adenoma recurrence | 25OHD | OR | 3 | 586 | 1366 | 0.87 (0.57 to 1.33) | 0.53 | 55 (0 to 86) | 0.35 |
| Cardiovascular outcomes | |||||||||
| Cardiovascular disease (prevalent) | 25OHD | OR | 16 | 7600 | 64 722 | 0.67 (0.55 to 0.82) | 9.7×10−5 | 74 (54 to 83) | 0.51 |
| Cardiovascular disease | 25OHD | RR | 19 | 6123 | 66 488 | 0.66 (0.57 to 0.77) | 1.6×10−7 | 61 (28 to 75) | 0.98 |
| Cardiovascular disease mortality | 25OHD | RR | 5 | 2007 | 24 387 | 0.55 (0.36 to 0.85) | 0.006 | 81 (40 to 90) | 0.09 |
| Hypertension | 25OHD | RR | 7 | 4965 | 48 633 | 0.70 (0.58 to 0.86) | 0.0004 | 44 (0 to 75) | 0.92 |
| Ischaemic heart disease | 25OHD | HR | 19 | 8376 | 82 982 | 0.72 (0.65 to 0.81) | 4.1×10−9 | 80 (69 to 86) | 0.27 |
| Ischaemic stroke (HR) | 25OHD | HR | 4 | 1800 | 26 596 | 0.66 (0.55 to 0.80) | 2.1×10−5 | 71 (0 to 86) | 0.63 |
| Ischaemic stroke (OR) | 25OHD | OR | 5 | 844 | 31 858 | 0.52 (0.44 to 0.61) | 2.3×10−14 | 0 (0 to 64) | 0.97 |
| Stroke | 25OHD | RR | 7 | 1214 | 39 095 | 0.61 (0.50 to 0.75) | 1.8×10−6 | 0 (0 to 58) | 0.94 |
HR=hazard ratio; MA=meta-analysis; NA=not applicable; OR=odds ratio; RR=relative risk.
P values were estimated using formulas presented in Altman and Bland 2011.140
*Effect estimate and 95% CI estimated on basis of random effects model. Reported effect estimates and 95% CI are presented for colon cancer (1,25(OH)2D) and colorectal cancer (1,25(OH)2D).