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1Department of Preventive Medicine, Chonnam National University Medical School, Hwasun, Korea
2Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
© 2023, Korean Society of Epidemiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
SNP | Chr | Nearby gene | Position |
EA | RA | CRP GWAS |
CRC GWAS |
|||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EAF | F | Beta | p-value | EAF | Overall mortality HD (/1,000 PY) | p-value | CRC mortality HD (/1,000 PY) | p-value | ||||||
rs2794520 | 1 | CRP | 159678816 | C | T | 0.365 | 961.9 | 0.247 | 7.23×10-200 | 0.366 | -0.230 | 0.887 | 0.018 | 0.989 |
rs12133641 | 1 | IL6R | 154428283 | G | A | 0.433 | 197.0 | -0.116 | 3.52×10-47 | 0.429 | -1.860 | 0.210 | -0.454 | 0.701 |
rs71086917 | 1 | LINC02819 | 159455503 | insA | - | 0.452 | 61.2 | -0.064 | 6.54×10-16 | 0.414 | 0.127 | 0.938 | 0.934 | 0.493 |
rs1260326 | 2 | GCKR | 27730940 | C | T | 0.450 | 133.0 | -0.090 | 1.31×10-29 | 0.452 | 3.017 | 0.050 | 1.535 | 0.201 |
rs7383869 | 7 | IL6 | 22748190 | A | G | 0.362 | 164.1 | 0.105 | 3.53×10-37 | 0.365 | 0.571 | 0.693 | 0.562 | 0.620 |
rs79320731 | 12 | HNF1A | 121422449 | CTGACTGGCACTCAGCA | T | 0.455 | 461.1 | -0.169 | 1.22×10-99 | 0.454 | -0.929 | 0.530 | -1.999 | 0.095 |
rs429358 | 19 | APOE | 45411941 | C | T | 0.096 | 587.6 | -0.321 | 3.53×10-125 | 0.057 | 8.684 | 0.011 | 7.331 | 0.014 |
Variables | Main analysis (7 serum CRP level-related SNPs) |
Sensitivity analysis (excluding rs429358) |
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---|---|---|---|---|---|---|---|---|---|
Overall mortality | p-value | CRC-specific | p-value | Overall mortality | p-value | CRC-specific mortality | p-value | ||
Using summary statistics |
|||||||||
IVW | -2.92 (-14.05, 8.21) | 0.607 | -0.76 (-9.61, 8.08) | 0.866 | 1.11 (-8.18, 10.40) | 0.815 | 2.40 (-4.51, 9.31) | 0.497 | |
Simple median | -0.93 (-13.67, 11.81) | 0.886 | 0.07 (-10.64, 10.78) | 0.989 | 2.25 (-9.74, 14.24) | 0.713 | 2.00 (-7.80, 11.80) | 0.689 | |
Weighted median | 1.43 (-8.96, 11.81) | 0.788 | 1.70 (-7.00, 10.41) | 0.701 | 3.39 (-7.00, 13.78) | 0.523 | 2.71 (-5.97, 11.39) | 0.540 | |
MR-Egger intercept | 0.92 (-3.29, 5.12) | 0.669 | 0.27 (-3.11, 3.65) | 0.876 | -0.57 (-4.21, 3.08) | 0.760 | -1.02 (-3.52, 1.49) | 0.426 | |
Using individual GRS |
|||||||||
GRS per 1 SD increment | -3.18 (-5.77, -0.59) | 0.016 | -2.09 (-4.26, 0.08) | 0.056 | 0.17 (-1.82, 2.16) | 0.870 | 0.11 (-1.49, 1.70) | 0.897 | |
GRS quintile | |||||||||
1st | 8.53 (1.12, 15.94) | 0.024 | 5.51 (-0.71, 11.73) | 0.082 | 1.94 (-4.47, 8.34) | 0.554 | 2.39 (-2.17, 6.95) | 0.349 | |
2nd | 1.86 (-5.16, 8.88) | 0.603 | 1.04 (-4.85, 6.93) | 0.730 | -2.15 (-8.56, 4.27) | 0.512 | -1.41 (-5.96, 3.14) | 0.598 | |
3rd | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||||
4th | -2.64 (-9.13, 3.85) | 0.425 | -1.54 (-6.68, 3.60) | 0.557 | -0.52 (-6.74, 5.70) | 0.870 | -2.06 (-6.53, 2.40) | 0.417 | |
5th | 1.14 (-5.17, 7.45) | 0.723 | 0.99 (-4.12, 6.09) | 0.705 | 2.00 (-4.45, 8.45) | 0.554 | 3.16 (-1.45, 7.77) | 0.229 |
Variables | Non-metastatic CRC |
Metastatic CRC |
|||||||
---|---|---|---|---|---|---|---|---|---|
Overall mortality | p-value | CRC-specific mortality | p-value | Overall mortality | p-value | CRC-specific mortality | p-value | ||
Using summary statistics |
|||||||||
IVW | 1.73 (-6.95, 10.41) | 0.697 | 3.37 (-3.41, 10.15) | 0.330 | -27.69 (-95.81, 40.43) | 0.426 | -28.19 (-91.79, 35.42) | 0.385 | |
Simple median | 3.57 (-6.96, 14.09) | 0.506 | 2.96 (-5.93, 11.85) | 0.514 | -24.08 (-121.25, 73.10) | 0.627 | 8.90 (-85.99, 103.79) | 0.854 | |
Weighted median | 4.73 (-3.69, 13.16) | 0.271 | 5.11 (-1.29, 11.51) | 0.117 | -42.26 (-125.36, 40.83) | 0.319 | -30.04 (-108.51, 48.43) | 0.453 | |
MR-Egger intercept | 0.04 (-3.37, 3.44) | 0.984 | -0.68 (-3.24, 1.89) | 0.605 | 12.62 (-10.94, 36.18) | 0.294 | 12.53 (-9.56, 34.62) | 0.266 | |
Using individual GRS |
|||||||||
GRS per 1 SD increment | -1.74 (-3.95, 0.46) | 0.121 | -0.45 (-2.20, 1.30) | 0.613 | -18.65 (-42.48, 5.17) | 0.125 | -22.65 (-45.57, 0.27) | 0.053 | |
GRS quintile | |||||||||
1st | 3.00 (-3.48, 9.49) | 0.364 | 0.37 (-4.51, 5.26) | 0.881 | 61.88 (-5.52, 129.29) | 0.072 | 60.52 (-4.77, 125.81) | 0.069 | |
2nd | -2.96 (-8.76, 2.84) | 0.317 | -3.08 (-7.39, 1.22) | 0.160 | 45.84 (-14.95, 106.64) | 0.139 | 37.64 (-21.03, 96.31) | 0.209 | |
3rd | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |||||
4th | -0.76 (-6.00, 4.49) | 0.778 | 0.61 (-3.21, 4.43) | 0.755 | -31.00 (-80.02, 18.02) | 0.215 | -30.44 (-72.34,11.46) | 0.155 | |
5th | -0.87 (-6.38, 4.65) | 0.758 | -0.07 (-3.94, 3.80) | 0.972 | 17.10 (-35.25, 69.44) | 0.522 | 2.43 (-43.66, 48.53) | 0.918 |
SNP, single-nucleotide polymorphism; CRP, C-reactive protein; Chr, chromosome; CRC, colorectal cancer; EA, effective allele; EAF, effective allele frequency; GWAS, genome-wide association study; HD, hazard difference; PY, person-year; RA, reference allele. The positions of the SNPs were derived from GRCh37. Age, sex, study centers, survey years, and first 10 principal components were adjusted in all models. Age, sex, genotyping array, tumor, node, metastasis stage, and first 10 principal components were adjusted in all models.
Values are presented as hazard difference per 1,000 person-year (95% confidence interval). CRC, colorectal cancer; CRP, C-reactive protein; GRS, genetic risk score; IVW, inverse-variance weighted method; SD, standard deviation; SNP, single-nucleotide polymorphism. Results are expressed per 2-fold increase in serum CRP levels. Age, sex, genotyping array, and tumor, node, metastasis stage were adjusted.
Values are presented as hazard difference per 1,000 person-year (95% confidence interval). CRC, colorectal cancer; CRP, C-reactive protein; GRS, genetic risk score; IVW, inverse-variance weighted method; SD, standard deviation. Results are expressed per 2-fold increase in serum CRP levels. Age, sex, and genotyping array were adjusted.