Table 2.
MR estimates for glycemic traits and risk of colorectal cancer
| Glycemic trait | IVW random effects | P heterogeneity a | Weighted median | MR-Egger | MR-Egger intercept | MR-PRESSO |
||
|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | OR (95% CI) | OR (95% CI) | P b | OR (95% CI) | SNPs excluded | |||
| Fasting insulinc | ||||||||
| Colorectal cancer | ||||||||
| All | 1.65 (1.15 to 2.36) | 1.60 × 10−7 | 1.48 (1.01 to 2.16) | 1.39 (0.43 to 4.57) | .78 | 1.52 (1.11 to 2.10) | rs11727676 | |
| Men | 1.72 (1.05 to 2.80) | 5.70 × 10−7 | 1.72 (1.05 to 2.80) | 2.32 (0.47 to 11.02) | .7 | 1.55 (1.00 to 2.39) | rs11727676 | |
| Women | 1.65 (1.14 to 2.39) | .05 | 1.05 (0.66 to 1.70) | 0.68 (0.21 to 2.16) | .11 | No outliers | ||
| Colon cancer | ||||||||
| All | 1.73 (1.16 to 2.59) | 8.70 × 10−6 | 1.60 (1.04 to 2.46) | 1.63 (0.44 to 6.05) | .93 | 1.57 (1.12 to 2.23) | rs11727676 | |
| Men | 1.57 (0.96 to 2.59) | .003 | 1.22 (0.69 to 2.16) | 1.80 (0.36 to 9.03) | .86 | 1.39 (0.91 to 2.14) | rs11727676 | |
| Women | 1.92 (1.21 to 3.06) | .01 | 1.55 (0.88 to 2.75) | 1.35 (0.30 to 6.17) | .63 | No outliers | ||
| Proximal colon cancer | ||||||||
| All | 1.77 (1.14 to 2.75) | .005 | 2.05 (1.22 to 3.46) | 1.55 (0.37 to 6.49) | .85 | 1.62 (1.08 to 2.41) | rs11727676 | |
| Men | 1.43 (0.81 to 2.56) | .07 | 1.60 (0.78 to 3.29) | 1.34 (0.20 to 9.03) | .94 | No outliers | ||
| Women | 2.23 (1.34 to 3.67) | .16 | 2.23 (1.15 to 4.35) | 1.77 (0.34 to 9.21) | .77 | No outliers | ||
| Distal colon cancer | ||||||||
| All | 1.79 (1.08 to 2.94) | 1.50 × 10−4 | 2.03 (1.16 to 3.56) | 2.10 (0.41 to 10.49) | .84 | 1.62 (1.02 to 2.53) | rs11727676 | |
| Men | 1.79 (1.02 to 3.10) | .07 | 1.70 (0.83 to 3.42) | 2.66 (0.44 to 16.28) | .65 | No outliers | ||
| Women | 1.79 (0.95 to 3.39) | .01 | 1.77 (0.79 to 3.90) | 1.46 (0.18 to 11.59) | .84 | No outliers | ||
| Rectal cancer | ||||||||
| All | 1.72 (1.14 to 2.56) | .04 | 1.79 (1.07 to 3.00) | 1.19 (0.32 to 4.39) | .57 | No outliers | ||
| Men | 2.08 (1.14 to 3.78) | .003 | 2.16 (1.09 to 4.31) | 2.66 (0.38 to 18.17) | .79 | 2.34 (1.34 to 4.06) | rs73013411 | |
| Women | 1.39 (0.81 to 2.39) | .3 | 1.86 (0.87 to 3.94) | 0.46 (0.08 to 2.56) | .18 | No outliers | ||
| 2-hour glucosec | ||||||||
| Colorectal cancer | ||||||||
| All | 1.02 (0.86 to 1.21) | 6.40 × 10−7 | 1.05 (0.92 to 1.20) | 0.82 (0.52 to 1.28) | .3 | 1.12 (0.99 to 1.27) | rs1260326, rs117643180 | |
| Men | 0.97 (0.81 to 1.17) | 9.90 × 10−4 | 1.06 (0.90 to 1.25) | 0.75 (0.45 to 1.23) | .26 | 1.02 (0.87 to 1.20) | rs1260326 | |
| Women | 1.06 (0.90 to 1.26) | .01 | 1.07 (0.90 to 1.26) | 0.90 (0.57 to 1.45) | .47 | No outliers | ||
| Colon cancer | ||||||||
| All | 1.00 (0.84 to 1.17) | 3 × 10−4 | 1.02 (0.88 to 1.19) | 0.79 (0.50 to 1.23) | .28 | 1.03 (0.89 to 1.20) | rs1260326 | |
| Men | 0.98 (0.84 to 1.15) | .14 | 1.02 (0.84 to 1.25) | 0.78 (0.50 to 1.22) | .28 | No outliers | ||
| Women | 1.02 (0.83 to 1.26) | .003 | 0.99 (0.81 to 1.21) | 0.81 (0.45 to 1.46) | .41 | No outliers | ||
| Proximal colon cancer | ||||||||
| All | 0.98 (0.85 to 1.12) | .26 | 0.90 (0.75 to 1.06) | 0.77 (0.54 to 1.11) | .17 | No outliers | ||
| Men | 0.95 (0.79 to 1.14) | .69 | 0.94 (0.73 to 1.21) | 0.90 (0.55 to 1.48) | .84 | No outliers | ||
| Women | 1.01 (0.84 to 1.22) | .22 | 1.00 (0.79 to 1.27) | 0.70 (0.43 to 1.16) | .13 | No outliers | ||
| Distal colon cancer | ||||||||
| All | 1.04 (0.84 to 1.30) | 5.00 × 10−4 | 1.03 (0.85 to 1.25) | 0.87 (0.47 to 1.58) | .52 | 1.11 (0.93 to 1.31) | rs1260326 | |
| Men | 1.04 (0.84 to 1.30) | .09 | 0.96 (0.75 to 1.23) | 0.79 (0.43 to 1.46) | .34 | No outliers | ||
| Women | 1.05 (0.77 to 1.42) | 9.00 × 10−4 | 0.97 (0.73 to 1.28) | 0.98 (0.40 to 2.36) | .86 | 1.12 (0.84 to 1.48) | rs1260326 | |
| Rectal cancer | ||||||||
| All | 1.05 (0.89 to 1.26) | .02 | 1.06 (0.89 to 1.27) | 0.84 (0.52 to 1.34) | .29 | No outliers | ||
| Men | 1.05 (0.84 to 1.32) | .03 | 1.03 (0.81 to 1.30) | 0.95 (0.50 to 1.82) | .74 | 1.12 (0.91 to 1.35) | rs1260326 | |
| Women | 1.05 (0.86 to 1.30) | .3 | 0.93 (0.71 to 1.21) | 0.74 (0.43 to 1.27) | .17 | No outliers | ||
| Fasting glucosec | ||||||||
| Colorectal cancer | ||||||||
| All | 1.04 (0.88 to 1.23) | 4.9 × 10−10 | 1.05 (0.89 to 1.25) | 1.01 (0.75 to 1.36) | .84 | 0.97 (0.84 to 1.12) | rs1260326, rs174583 | |
| Men | 0.90 (0.71 to 1.14) | 4.8 × 10−4 | 0.96 (0.72 to 1.30) | 1.03 (0.68 to 1.57) | .47 | 0.90 (0.76 to 1.07) | rs1260326, rs174583 | |
| Women | 1.11 (0.92 to 1.34) | .003 | 1.01 (0.80 to 1.28) | 1.02 (0.73 to 1.42) | .54 | 1.07 (0.90 to 1.27) | rs174583 | |
| Colon cancer | ||||||||
| All | 0.96 (0.79 to 1.16) | 1.40 × 10−7 | 0.90 (0.73 to 1.09) | 0.95 (0.68 to 1.34) | .96 | 0.93 (0.79 to 1.11) | rs174583 | |
| Men | 0.90 (0.71 to 1.14) | 4.80 × 10−4 | 0.97 (0.72 to 1.30) | 1.03 (0.68 to 1.57) | .47 | 0.90 (0.73 to 1.11) | rs1260326, rs174583 | |
| Women | 1.22 (0.83 to 1.26) | .02 | 0.87 (0.66 to 1.14) | 0.89 (0.61 to 1.30) | .37 | 0.99 (0.81 to 1.21) | rs174583 | |
| Proximal colon cancer | ||||||||
| All | 0.89 (0.73 to 1.06) | .04 | 0.82 (0.64 to 1.06) | 0.85 (0.61 to 1.19) | .78 | 0.87 (0.73 to 1.04) | rs174583 | |
| Men | 0.89 (0.68 to 1.16) | .1 | 0.92 (0.63 to 1.36) | 1.03 (0.64 to 1.65) | .47 | No outliers | ||
| Women | 0.88 (0.70 to 1.11) | .45 | 0.71 (0.51 to 1.00) | 0.72 (0.48 to 1.07) | .22 | No outliers | ||
| Distal colon cancer | ||||||||
| All | 1.05 (0.83 to 1.34) | 6 × 10−7 | 0.99 (0.75 to 1.30) | 0.97 (0.63 to 1.49) | .67 | 0.98 (0.80 to 1.20) | rs1260326, rs9348441, rs174583 | |
| Men | 0.94 (0.71 to 1.25) | .01 | 0.99 (0.68 to 1.43) | 0.98 (0.59 to 1.60) | .86 | 0.90 (0.70 to 1.16) | rs174583 | |
| Women | 1.19 (0.88 to 1.60) | .003 | 0.97 (0.66 to 1.42) | 0.94 (0.55 to 1.62) | .32 | 1.13 (0.85 to 1.51) | rs174583 | |
| Rectal cancer | ||||||||
| All | 1.17 (0.96 to 1.43) | .01 | 1.12 (0.85 to 1.48) | 1.03 (0.73 to 1.46) | .38 | 1.14 (0.94 to 1.38) | rs174583 | |
| Men | 1.11 (0.86 to 1.42) | .06 | 1.17 (0.83 to 1.65) | 1.05 (0.67 to 1.63) | .77 | No outliers | ||
| Women | 1.23 (0.96 to 1.60) | .54 | 1.00 (0.67 to 1.49) | 0.98 (0.63 to 1.54) | .21 | No outliers | ||
| Glycated hemoglobin (HbA1c)c | ||||||||
| Colorectal cancer | ||||||||
| All | 1.09 (1.00 to 1.19) | 2.80 × 10−21 | 1.06 (0.95 to 1.17) | 0.93 (0.78 to 1.11) | .04 | 1.06 (0.99 to 1.14) | rs9273363, rs174549, rs76895963, rs61927768, rs10784889, rs11065979 | |
| Men | 1.09 (0.98 to 1.21) | 4.80 × 10−9 | 1.06 (0.92 to 1.23) | 0.95 (0.77 to 1.18) | .16 | 1.07 (0.97 to 1.17) | rs3104369, rs76895963 | |
| Women | 1.09 (0.99 to 1.21) | 1.60 × 10−6 | 1.03 (0.90 to 1.20) | 0.91 (0.74 to 1.11) | .04 | 1.07 (0.97 to 1.17) | rs11065979 | |
| Colon cancer | ||||||||
| All | 1.06 (0.95 to 1.17) | 8.00 × 10−17 | 1.05 (0.92 to 1.20) | 0.94 (0.77 to 1.15) | .2 | 1.03 (0.95 to 1.13) | rs174549, rs61927768, rs10784889, rs11065979 | |
| Men | 1.08 (0.95 to 1.23) | 5.60 × 10−9 | 1.03 (0.86 to 1.23) | 0.95 (0.72 to 1.24) | .28 | 1.08 (0.95 to 1.22) | rs3104369, rs76895963 | |
| Women | 1.05 (0.94 to 1.17) | 9.80 × 10−4 | 1.01 (0.84 to 1.20) | 0.94 (0.75 to 1.18) | .28 | 1.03 (0.93 to 1.15) | rs11065979 | |
| Proximal colon cancer | ||||||||
| All | 1.06 (0.95 to 1.19) | 1.20 × 10−9 | 1.00 (0.85 to 1.17) | 0.87 (0.69 to 1.10) | .06 | 1.06 (0.95 to 1.17) | rs10784889, rs11065979 | |
| Men | 1.10 (0.94 to 1.28) | 2.40 × 10−4 | 1.06 (0.85 to 1.33) | 0.94 (0.67 to 1.26) | .19 | 1.08 (0.94 to 1.26) | rs3104369 | |
| Women | 1.03 (0.90 to 1.18) | .01 | 1.04 (0.84 to 1.30) | 0.83 (0.63 to 1.09) | .06 | No outliers | ||
| Distal colon cancer | ||||||||
| All | 1.08 (0.96 to 1.22) | 1.90 × 10−10 | 0.96 (0.82 to 1.14) | 1.07 (0.83 to 1.36) | .9 | 1.07 (0.96 to 1.19) | rs7766070, rs174549, rs61927768, rs11065979 | |
| Men | 1.07 (0.92 to 1.26) | 3.80 × 10−7 | 1.02 (0.81 to 1.29) | 0.99 (0.72 to 1.40) | .61 | 1.06 (0.90 to 1.24) | rs3104369 | |
| Women | 1.09 (0.94 to 1.26) | .01 | 1.06 (0.84 to 1.32) | 1.13 (0.83 to 1.53) | .79 | 1.08 (0.94 to 1.25) | rs11065979 | |
| Rectal cancer | ||||||||
| All | 1.19 (1.06 to 1.33) | 1.60 × 10−6 | 1.07 (0.95 to 1.30) | 1.03 (0.82 to 1.30) | .16 | 1.14 (1.03 to 1.27) | rs9273363, rs61927768, rs11065979 | |
| Men | 1.21 (1.05 to 1.40) | 5.90 × 10−4 | 1.37 (1.11 to 1.70) | 1.26 (0.94 to 1.69) | .77 | No outliers | ||
| Women | 1.16 (0.99 to 1.35) | .01 | 0.95 (0.75 to 1.22) | 0.78 (0.57 to 1.06) | .004 | 1.14 (0.98 to 1.32) | rs3130453 | |
| Type 2 diabetesd | ||||||||
| Colorectal cancer | ||||||||
| All | 1.04 (1.01 to 1.07) | 1.90 × 10−16 | 1.00 (0.96 to 1.04) | 0.97 (0.90 to 1.04) | .04 | 1.04 (1.01 to 1.07) | rs1260326, rs9379084, rs7756992, rs76895963 | |
| Men | 1.02 (0.98 to 1.06) | 1.30 × 10−6 | 1.00 (0.94 to 1.05) | 0.96 (0.88 to 1.05) | .15 | 1.02 (0.99 to 1.06) | rs76895963, rs2736177 | |
| Women | 1.06 (1.02 to 1.09) | 4.00 × 10−6 | 0.99 (0.94 to 1.05) | 0.98 (0.90 to 1.07) | .06 | 1.07 (1.03 to 1.11) | rs7756992 | |
| Colon cancer | ||||||||
| All | 1.03 (1.00 to 1.07) | 3.30 × 10−10 | 0.98 (0.94 to 1.03) | 0.97 (0.90 to 1.05) | .08 | 1.04 (1.01 to 1.08) | rs7756992, rs1561927 | |
| Men | 1.01 (0.97 to 1.06) | .002 | 0.98 (0.91 to 1.05) | 0.93 (0.85 to 1.03) | .08 | 1.02 (0.98 to 1.07) | rs76895963 | |
| Women | 1.05 (1.01 to 1.09) | 1.20 × 10−4 | 1.01 (0.94 to 1.07) | 1.01 (0.91 to 1.12) | .34 | 1.06 (1.02 to 1.11) | rs7756992 | |
| Proximal colon cancer | ||||||||
| All | 1.03 (0.99 to 1.07) | 4.20 × 10−5 | 0.97 (0.92 to 1.03) | 0.96 (0.88 to 1.05) | .1 | 1.03 (0.99 to 1.06) | rs6518681 | |
| Men | 1.01 (0.96 to 1.06) | .47 | 1.02 (0.94 to 1.11) | 0.93 (0.83 to 1.04) | .12 | No outliers | ||
| Women | 1.05 (1.00 to 1.11) | .002 | 1.00 (0.91 to 1.08) | 1.00 (0.89 to 1.13) | .31 | No outliers | ||
| Distal colon cancer | ||||||||
| All | 1.04 (1.00 to 1.08) | 1.25 × 10−7 | 1.04 (0.98 to 1.11) | 0.98 (0.89 to 1.08) | .19 | 1.05 (1.01 to 1.09) | rs7756992, rs2736177, rs10811647 | |
| Men | 1.02 (0.97 to 1.08) | .002 | 0.95 (0.88 to 1.04) | 0.95 (0.84 to 1.07) | .21 | No outliers | ||
| Women | 1.06 (1.01 to 1.13) | 1.70 × 10−4 | 1.02 (0.92 to 1.12) | 1.03 (0.90 to 1.17) | .56 | No outliers | ||
| Rectal cancer | ||||||||
| All | 1.04 (1.00 to 1.08) | 2.90 × 10−7 | 1.00 (0.93 to 1.07) | 0.97 (0.88 to 1.07) | .11 | 1.04 (1.00 to 1.08) | rs149717632 | |
| Men | 1.03 (0.97 to 1.08) | .001 | 1.03 (0.94 to 1.13) | 0.98 (0.87 to 1.11) | .41 | 1.02 (0.97 to 1.08) | rs149717632 | |
| Women | 1.06 (1.00 to 1.12) | .004 | 0.99 (0.90 to 1.08) | 0.96 (0.84 to 1.09) | .1 | No outliers | ||
a
Cochran’s Q statistics (2-sided) quantified heterogeneity across individual SNPs. CI = confidence interval; IVW = inverse-variance-weighted; MR = Mendelian randomization; OR = odds ratio; PRESSO = pleiotropy residual sum and outlier test; SNP = single nucleotide polymorphism.
b
MR-Egger intercept test (2-sided P value).
c
Odds ratios scaled to 1-SD increase in log of genetically predicted 2-hour glucose, fasting glucose, glycated hemoglobin, and fasting insulin levels.
d
Odds ratios scaled to 1-unit increase in log odds of genetic liability to type 2 diabetes.