{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:01:57Z","timestamp":1786982517614,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Macao Polytechnic University","award":["RP\/FCA-15\/2022"],"award-info":[{"award-number":["RP\/FCA-15\/2022"]}]},{"name":"Macao Polytechnic University","award":["RP\/FCA-15\/2022"],"award-info":[{"award-number":["RP\/FCA-15\/2022"]}]},{"name":"Macao Polytechnic University","award":["RP\/FCA-15\/2022"],"award-info":[{"award-number":["RP\/FCA-15\/2022"]}]},{"name":"Macao Polytechnic University","award":["RP\/FCA-15\/2022"],"award-info":[{"award-number":["RP\/FCA-15\/2022"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-024-01684-9","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T10:08:40Z","timestamp":1734516520000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comprehensive Mendelian randomization analysis of low-density lipoprotein cholesterol and multiple cancers"],"prefix":"10.1007","volume":"15","author":[{"given":"Hengchang","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinquan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"1684_CR1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12944-020-01204-y","volume":"19","author":"M Hedayatnia","year":"2020","unstructured":"Hedayatnia M, Asadi Z, Zare-Feyzabadi R, et al. Dyslipidemia and cardiovascular disease risk among the MASHAD study population. Lipids Health Dis. 2020;19:42. https:\/\/doi.org\/10.1186\/s12944-020-01204-y.","journal-title":"Lipids Health Dis"},{"key":"1684_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.803473","volume":"12","author":"C-F Deng","year":"2022","unstructured":"Deng C-F, Zhu N, Zhao T-J, Li H-F, Gu J, Liao D-F, Qin L. Involvement of LDL and ox-LDL in cancer development and its therapeutical potential. Front Oncol. 2022;12: 803473. https:\/\/doi.org\/10.3389\/fonc.2022.803473.","journal-title":"Front Oncol"},{"key":"1684_CR3","unstructured":"World Health Organization. Cancer. 2024. https:\/\/www.who.int\/health-topics\/cancer#tab=tab_1"},{"key":"1684_CR4","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12944-021-01562-1","volume":"20","author":"G Mazzuferi","year":"2021","unstructured":"Mazzuferi G, Bacchetti T, Islam MO, et al. High density lipoproteins and oxidative stress in breast cancer. Lipids Health Dis. 2021;20:143. https:\/\/doi.org\/10.1186\/s12944-021-01562-1.","journal-title":"Lipids Health Dis"},{"key":"1684_CR5","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13058-022-01508-0","volume":"24","author":"L Sun","year":"2022","unstructured":"Sun L, Ding H, Jia Y, et al. Associations of genetically proxied inhibition of HMG-CoA reductase, NPC1L1, and PCSK9 with breast cancer and prostate cancer. Breast Cancer Res. 2022;24:12. https:\/\/doi.org\/10.1186\/s13058-022-01508-0.","journal-title":"Breast Cancer Res"},{"issue":"10","key":"1684_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046691","volume":"7","author":"D Bansal","year":"2012","unstructured":"Bansal D, Undela K, D\u2019Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS ONE. 2012;7(10): e46691. https:\/\/doi.org\/10.1371\/journal.pone.0046691.","journal-title":"PLoS ONE"},{"issue":"11","key":"1684_CR7","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1002\/cncr.20271","volume":"100","author":"DM Boudreau","year":"2004","unstructured":"Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR. The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case-control study. Cancer. 2004;100(11):2308\u201316. https:\/\/doi.org\/10.1002\/cncr.20271.","journal-title":"Cancer"},{"issue":"R1","key":"1684_CR8","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","volume":"23","author":"GD Smith","year":"2014","unstructured":"Smith GD, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23(R1):R89\u201398. https:\/\/doi.org\/10.1093\/hmg\/ddu328.","journal-title":"Hum Mol Genet"},{"issue":"8","key":"1684_CR9","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/sim.3034","volume":"27","author":"DA Lawlor","year":"2008","unstructured":"Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey SG. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133\u201363. https:\/\/doi.org\/10.1002\/sim.3034.","journal-title":"Stat Med"},{"key":"1684_CR10","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","volume":"362","author":"NM Davies","year":"2018","unstructured":"Davies NM, Holmes MV, Davey SG. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018;362: k601. https:\/\/doi.org\/10.1136\/bmj.k601.","journal-title":"BMJ"},{"issue":"22","key":"1684_CR11","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1056\/nejmoa1604304","volume":"375","author":"BA Ference","year":"2016","unstructured":"Ference BA, Robinson JG, Brook RD, Catapano AL, Chapman MJ, Neff D, Sabatine MS. Variation inpcsk9andhmgcrand risk of cardiovascular disease and diabetes. N Engl J Med. 2016;375(22):2144\u201353. https:\/\/doi.org\/10.1056\/nejmoa1604304.","journal-title":"N Engl J Med"},{"issue":"8","key":"1684_CR12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1089\/154099903322447710","volume":"12","author":"JA Cauley","year":"2003","unstructured":"Cauley JA, Zmuda JM, Lui LY, Hillier TA, Ness RB, Stone KL, Bauer DC. Lipid-lowering drug use and breast cancer in older women: a prospective study. J Women\u2019s Health. 2003;12(8):749\u201356. https:\/\/doi.org\/10.1089\/154099903322447710.","journal-title":"J Women's Health"},{"key":"1684_CR13","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1186\/s13046-022-02477-0","volume":"41","author":"L Wang","year":"2022","unstructured":"Wang L, Li S, Luo H, et al. PCSK9 promotes the progression and metastasis of colon cancer cells through regulation of EMT and PI3K\/AKT signaling in tumor cells and phenotypic polarization of macrophages. J Exp Clin Cancer Res. 2022;41:303. https:\/\/doi.org\/10.1186\/s13046-022-02477-0.","journal-title":"J Exp Clin Cancer Res"},{"key":"1684_CR14","doi-asserted-by":"publisher","unstructured":"Elsworth B, Lyon M, Alexander T, Liu Y, Matthews P, Hallett J, Hemani G. The mrc ieu opengwas data infrastructure. 2020. https:\/\/doi.org\/10.1101\/2020.08.10.244293","DOI":"10.1101\/2020.08.10.244293"},{"key":"1684_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114654","volume":"196","author":"KK Patel","year":"2022","unstructured":"Patel KK, Kashfi K. Lipoproteins and cancer: the role of hdl-c, ldl-c, and cholesterol-lowering drugs. Biochem Pharmacol. 2022;196: 114654. https:\/\/doi.org\/10.1016\/j.bcp.2021.114654.","journal-title":"Biochem Pharmacol"},{"key":"1684_CR16","doi-asserted-by":"publisher","first-page":"11153","DOI":"10.3390\/ijms241311153","volume":"24","author":"G Revilla","year":"2023","unstructured":"Revilla G, Ruiz-Auladell L, Vallverd\u00fa NF, Santamar\u00eda P, Moral A, P\u00e9rez JI, Li C, Fuste V, Lerma E, Corcoy R, et al. Low-density lipoprotein receptor is a key driver of aggressiveness in thyroid tumor cells. Int J Mol Sci. 2023;24:11153. https:\/\/doi.org\/10.3390\/ijms241311153.","journal-title":"Int J Mol Sci"},{"key":"1684_CR17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s12672-016-0262-5","volume":"7","author":"AE Baek","year":"2016","unstructured":"Baek AE, Nelson ER. The contribution of cholesterol and its metabolites to the pathophysiology of breast cancer. HORM CANC. 2016;7:219\u201328. https:\/\/doi.org\/10.1007\/s12672-016-0262-5.","journal-title":"HORM CANC"},{"key":"1684_CR18","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1200\/JCO.2010.31.5200","volume":"29","author":"CM Kitahara","year":"2011","unstructured":"Kitahara CM, et al. Total cholesterol and cancer risk in a large prospective study in Korea. JCO. 2011;29:1592\u20138. https:\/\/doi.org\/10.1200\/JCO.2010.31.5200.","journal-title":"JCO"},{"key":"1684_CR19","doi-asserted-by":"publisher","first-page":"e052373","DOI":"10.1136\/bmjopen-2021-052373","volume":"12","author":"Z Yang","year":"2022","unstructured":"Yang Z, Tang H, Lu S, et al. Relationship between serum lipid level and colorectal cancer: a systemic review and meta-analysis. BMJ Open. 2022;12:e052373. https:\/\/doi.org\/10.1136\/bmjopen-2021-052373.","journal-title":"BMJ Open"},{"key":"1684_CR20","doi-asserted-by":"publisher","first-page":"104847","DOI":"10.1016\/j.phrs.2020.104847","volume":"158","author":"KS Abdelwahed","year":"2020","unstructured":"Abdelwahed KS, Siddique AB, Mohyeldin MM, Qusa MH, Goda AA, Singh SS, Sayed KAE. Pseurotin a as a novel suppressor of hormone dependent breast cancer progression and recurrence by inhibiting pcsk9 secretion and interaction with ldl receptor. Pharmacol Res. 2020;158:104847. https:\/\/doi.org\/10.1016\/j.phrs.2020.104847.","journal-title":"Pharmacol Res"},{"issue":"1","key":"1684_CR21","doi-asserted-by":"publisher","DOI":"10.21542\/gcsp.2017.2","volume":"2017","author":"NG Seidah","year":"2017","unstructured":"Seidah NG. The PCSK9 revolution and the potential of PCSK9-based therapies to reduce LDL-cholesterol. Glob Cardiol Sci Pract. 2017;2017(1): e201702. https:\/\/doi.org\/10.21542\/gcsp.2017.2.","journal-title":"Glob Cardiol Sci Pract"},{"key":"1684_CR22","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/genes15010132","volume":"15","author":"W Wang","year":"2024","unstructured":"Wang W, Li W, Zhang D, Mi Y, Zhang J, He G. The causal relationship between PCSK9 inhibitors and malignant tumors: a mendelian randomization study based on drug targeting. Genes. 2024;15:132. https:\/\/doi.org\/10.3390\/genes15010132.","journal-title":"Genes"},{"issue":"1","key":"1684_CR23","doi-asserted-by":"publisher","first-page":"3971","DOI":"10.1038\/s41467-022-31663-z.PMID:35803966;PMCID:PMC9270407","volume":"13","author":"CC Wong","year":"2022","unstructured":"Wong CC, Wu JL, Ji F, Kang W, Bian X, Chen H, Chan LS, Luk STY, Tong S, Xu J, Zhou Q, Liu D, Su H, Gou H, Cheung AH, To KF, Cai Z, Shay JW, Yu J. The cholesterol uptake regulator PCSK9 promotes and is a therapeutic target in APC\/KRAS-mutant colorectal cancer. Nat Commun. 2022;13(1):3971. https:\/\/doi.org\/10.1038\/s41467-022-31663-z.PMID:35803966;PMCID:PMC9270407.","journal-title":"Nat Commun"},{"issue":"7","key":"1684_CR24","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","volume":"37","author":"S Burgess","year":"2013","unstructured":"Burgess S, Butterworth AS, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658\u201365. https:\/\/doi.org\/10.1002\/gepi.21758.","journal-title":"Genet Epidemiol"},{"issue":"7414","key":"1684_CR25","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JPT Higgins","year":"2003","unstructured":"Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557\u201360. https:\/\/doi.org\/10.1136\/bmj.327.7414.557.","journal-title":"BMJ"},{"issue":"21","key":"1684_CR26","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1056\/nejmoa0807646","volume":"359","author":"PM Ridker","year":"2008","unstructured":"Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Glynn RJ. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med. 2008;359(21):2195\u2013207. https:\/\/doi.org\/10.1056\/nejmoa0807646.","journal-title":"N Engl J Med"},{"key":"1684_CR27","doi-asserted-by":"publisher","first-page":"4502","DOI":"10.3390\/cancers15184502","volume":"15","author":"L Lippi","year":"2023","unstructured":"Lippi L, Turco A, Moalli S, Gallo M, Curci C, Maconi A, de Sire A, Invernizzi M. Role of prehabilitation and rehabilitation on functional recovery and quality of life in thyroid cancer patients: a comprehensive review. Cancers. 2023;15:4502. https:\/\/doi.org\/10.3390\/cancers15184502.","journal-title":"Cancers"},{"issue":"2","key":"1684_CR28","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden J. George Davey Smith, Stephen Burgess, Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512\u201325. https:\/\/doi.org\/10.1093\/ije\/dyv080.","journal-title":"Int J Epidemiol"},{"key":"1684_CR29","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","volume":"32","author":"S Burgess","year":"2017","unstructured":"Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377\u201389. https:\/\/doi.org\/10.1007\/s10654-017-0255-x.","journal-title":"Eur J Epidemiol"},{"issue":"4","key":"1684_CR30","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden J, Smith GD, Haycock P, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304\u201314. https:\/\/doi.org\/10.1002\/gepi.21965.","journal-title":"Genet Epidemiol"},{"key":"1684_CR31","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/nrc1751","volume":"5","author":"MF Demierre","year":"2005","unstructured":"Demierre MF, Higgins P, Gruber S, et al. Statins and cancer prevention. Nat Rev Cancer. 2005;5:930\u201342. https:\/\/doi.org\/10.1038\/nrc1751.","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"1684_CR32","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1093\/carcin\/bgx058","volume":"38","author":"KH Stopsack","year":"2017","unstructured":"Stopsack KH, Gerke TA, Andr\u00e9n O, Andersson SO, Giovannucci EL, Mucci LA, Rider JR. Cholesterol uptake and regulation in high-grade and lethal prostate cancers. Carcinogenesis. 2017;38(8):806\u201311. https:\/\/doi.org\/10.1093\/carcin\/bgx058.","journal-title":"Carcinogenesis"},{"key":"1684_CR33","doi-asserted-by":"publisher","first-page":"527","DOI":"10.3390\/nu16040527","volume":"16","author":"S Pietrzak","year":"2024","unstructured":"Pietrzak S, Marciniak W, Derkacz R, Matuszczak M, Kilja\u0144czyk A, Baszuk P, Bry\u015bkiewicz M, Sikorski A, Gronwald J, S\u0142ojewski M, et al. Correlation between selenium and zinc levels and survival among prostate cancer patients. Nutrients. 2024;16:527. https:\/\/doi.org\/10.3390\/nu16040527.","journal-title":"Nutrients"},{"key":"1684_CR34","doi-asserted-by":"publisher","first-page":"841","DOI":"10.3390\/antiox13070841","volume":"13","author":"M Matuszczak","year":"2024","unstructured":"Matuszczak M, Kilja\u0144czyk A, Marciniak W, Derkacz R, Stempa K, Baszuk P, Bry\u015bkiewicz M, Cybulski C, D\u0119bniak T, Gronwald J, et al. Antioxidant properties of zinc and copper\u2014blood zinc-to copper-ratio as a marker of cancer risk BRCA1 mutation carriers. Antioxidants. 2024;13:841. https:\/\/doi.org\/10.3390\/antiox13070841.","journal-title":"Antioxidants"},{"key":"1684_CR35","doi-asserted-by":"publisher","first-page":"3373","DOI":"10.3390\/cancers13133373","volume":"13","author":"M Matuszczak","year":"2021","unstructured":"Matuszczak M, Schalken JA, Salagierski M. Prostate cancer liquid biopsy biomarkers\u2019 clinical utility in diagnosis and prognosis. Cancers. 2021;13:3373. https:\/\/doi.org\/10.3390\/cancers13133373.","journal-title":"Cancers"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-024-01684-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-024-01684-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-024-01684-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T11:17:30Z","timestamp":1734520650000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-024-01684-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1684"],"URL":"https:\/\/doi.org\/10.1007\/s12672-024-01684-9","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]},"assertion":[{"value":"23 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol and data collection for the original GWAS were approved by the relevant ethics committees and written informed consent was obtained from each participant prior to data collection. Therefore, no additional ethical approval was required for the use of data in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"798"}}