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A Mendelian randomization study of the effects of blood lipids on breast cancer risk
Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.ORCID iD: 0000-0002-6933-4637
2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, no 1, article id 3957Article in journal (Refereed) Published
Abstract [en]

Observational studies have reported inconsistent associations between circulating lipids and breast cancer risk. Using results from >400,000 participants in two-sample Mendelian randomization, we show that genetically raised LDL-cholesterol is associated with higher risk of breast cancer (odds ratio, OR, per standard deviation, 1.09, 95% confidence interval, 1.02-1.18, P = 0.020) and estrogen receptor (ER)-positive breast cancer (OR 1.14 [1.05-1.24] P = 0.004). Genetically raised HDL-cholesterol is associated with higher risk of ER-positive breast cancer (OR 1.13 [1.01-1.26] P = 0.037). HDL-cholesterol-raising variants in the gene encoding the target of CETP inhibitors are associated with higher risk of breast cancer (OR 1.07 [1.03-1.11] P = 0.001) and ER-positive breast cancer (OR 1.08 [1.03-1.13] P = 0.001). LDL-cholesterol-lowering variants mimicking PCSK9 inhibitors are associated (P = 0.014) with lower breast cancer risk. We find no effects related to the statin and ezetimibe target genes. The possible risk-promoting effects of raised LDL-cholesterol and CETP-mediated raised HDL-cholesterol have implications for breast cancer prevention and clinical trials.

Place, publisher, year, edition, pages
2018. Vol. 9, no 1, article id 3957
National Category
Clinical Medicine
Research subject
Health and Welfare
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URN: urn:nbn:se:du-28660DOI: 10.1038/s41467-018-06467-9ISI: 000445819400008PubMedID: 30262900Scopus ID: 2-s2.0-85054088248OAI: oai:DiVA.org:du-28660DiVA, id: diva2:1253554
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-16Bibliographically approved

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Ärnlöv, Johan

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