A Mendelian randomization analysis of circulating lipid traits and breast cancer risk.
Breast cancer
Mendelian randomization
cholesterol
epidemiology
genetics
instrumental variable
lipids
Journal
International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
accepted:
05
11
2019
pubmed:
25
12
2019
medline:
28
4
2021
entrez:
25
12
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31872213
pii: 5686031
doi: 10.1093/ije/dyz242
pmc: PMC7750975
doi:
Substances chimiques
Lipids
0
Triglycerides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1117-1131Subventions
Organisme : Cancer Research UK
ID : 10124
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : HHSN268201600002C
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA070867
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA160056
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600003C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600004C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201600001C
Pays : United States
Organisme : Cancer Research UK
ID : 10118
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 10119
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 29186
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : HHSN268201600018C
Pays : United States
Informations de copyright
© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
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