A Mendelian randomization analysis of circulating lipid traits and breast cancer risk

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Breast Canc Assoc Consortium , Beeghly-Fadiel , A , Khankari , N K , Delahanty , R J , Zheng , W , Blomqvist , C & Nevanlinna , H 2020 , ' A Mendelian randomization analysis of circulating lipid traits and breast cancer risk ' , International Journal of Epidemiology , vol. 49 , no. 4 , pp. 1117-1131 . https://doi.org/10.1093/ije/dyz242

Title: A Mendelian randomization analysis of circulating lipid traits and breast cancer risk
Author: Breast Canc Assoc Consortium; Beeghly-Fadiel, Alicia; Khankari, Nikhil K.; Delahanty, Ryan J.; Zheng, Wei; Blomqvist, Carl; Nevanlinna, Heli
Contributor organization: HUS Comprehensive Cancer Center
Department of Oncology
HUS Gynecology and Obstetrics
Department of Obstetrics and Gynecology
Date: 2020-08
Language: eng
Number of pages: 15
Belongs to series: International Journal of Epidemiology
ISSN: 0300-5771
DOI: https://doi.org/10.1093/ije/dyz242
URI: http://hdl.handle.net/10138/338505
Abstract: Background: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. Methods: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. Results: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. Conclusions: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.
Subject: Breast cancer
Mendelian randomization
instrumental variable
3142 Public health care science, environmental and occupational health
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion

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