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| 005 | 20250113113006.0 | ||
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| 100 | 1 | _ | |a Chan, Wing Ching |0 0000-0001-7090-6551 |b 0 |
| 245 | _ | _ | |a Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study. |
| 260 | _ | _ | |a Edinburgh |c 2025 |b Nature Publ. Group |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a 2025 Jan;132(1):103-110 |
| 520 | _ | _ | |a Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls). Our main analysis was a multivariable MR (MVMR) with mutual adjustments for LDL-C, HDL-C, and triglycerides. Secondary analyses, including MVMR additionally-adjusting for BMI or diabetes, were also performed.Genetically-predicted LDL-C was positively associated with CRC risk in the MVMR adjusted for HDL-C and triglycerides (OR = 1.09; 95%CI 1.02-1.16 per SD increase) and additionally-adjusted for BMI (OR = 1.12; 95%CI 1.05-1.21) or diabetes (OR = 1.09; 95%CI 1.02-1.17). Associations were generally consistent across anatomical subsites. No clear evidence of association was found for other lipids, lipoproteins, or LDL-lowering drug-targets.We found evidence of a weak positive association between LDL-C and CRC that did not appear to be explained by potential pleiotropic pathways such as via HDL-C, triglycerides, BMI, or diabetes. |
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| 700 | 1 | _ | |a Liu, Lili |b 1 |
| 700 | 1 | _ | |a Bouras, Emmanouil |0 0000-0003-1489-5506 |b 2 |
| 700 | 1 | _ | |a Zuber, Verena |b 3 |
| 700 | 1 | _ | |a Wen, Wanqing |b 4 |
| 700 | 1 | _ | |a Long, Jirong |b 5 |
| 700 | 1 | _ | |a Gill, Dipender |0 0000-0001-7312-7078 |b 6 |
| 700 | 1 | _ | |a Murphy, Neil |0 0000-0003-3347-8249 |b 7 |
| 700 | 1 | _ | |a Gunter, Marc J |b 8 |
| 700 | 1 | _ | |a Assimes, Themistocles L |0 0000-0003-2349-0009 |b 9 |
| 700 | 1 | _ | |a Bujanda, Luis |b 10 |
| 700 | 1 | _ | |a Gruber, Stephen B |0 0000-0001-8656-7822 |b 11 |
| 700 | 1 | _ | |a Küry, Sébastien |0 0000-0001-5497-0465 |b 12 |
| 700 | 1 | _ | |a Lynch, Brigid M |0 0000-0001-8060-547X |b 13 |
| 700 | 1 | _ | |a Qu, Conghui |b 14 |
| 700 | 1 | _ | |a Thomas, Minta |0 0000-0001-9337-7015 |b 15 |
| 700 | 1 | _ | |a White, Emily |b 16 |
| 700 | 1 | _ | |a Woods, Michael O |b 17 |
| 700 | 1 | _ | |a Peters, Ulrike |0 0000-0001-5666-9318 |b 18 |
| 700 | 1 | _ | |a Li, Christopher I |b 19 |
| 700 | 1 | _ | |a Chan, Andrew T |0 0000-0001-7284-6767 |b 20 |
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| 700 | 1 | _ | |a Tsilidis, Konstantinos K |0 0000-0002-8452-8472 |b 22 |
| 700 | 1 | _ | |a Zheng, Wei |b 23 |
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