Associations Boston Va Healthcare Program, Boston, Massachusetts, United states, Cardio to have Genomic Drug, Massachusetts General Hospital, Harvard Medical University, Boston, Massachusetts, Us, Program inside Medical and you may Populace Family genes, Wider Institute of MIT and you can Harvard, Cambridge, Massachusetts, United states
Affiliations Corporal Michael Crescenz Va Medical, Philadelphia, Pennsylvania, United states of america, Department from Operations, Perelman University away from Medication, College out of Pennsylvania, Philadelphia, Pennsylvania, United states of america
Affiliations Corporal Michael Crescenz Virtual assistant Medical facility, Philadelphia, Pennsylvania, Usa, Agency out of Medicine, Perelman School out-of Drug, College regarding Pennsylvania, Philadelphia, Pennsylvania, United states
Affiliations Va Palo Alto Medical care Program, Palo Alto, Ca, U . s ., Institution away from Medicine, Stanford College College or university regarding Drug, Stanford, California, United states of america
Associations Virtual assistant Palo Alto Healthcare System, Palo Alto, Ca, U . s ., Department away from Drug, Stanford College College or university away from Medicine, Stanford, California, Usa
Associations Department away from Medication, Perelman University of Medicine, School away from Pennsylvania, Philadelphia, Pennsylvania, Usa, Service out-of Genes, Perelman College of Treatments, School off Pennsylvania, Philadelphia, Pennsylvania, Us
Opportunities Conceptualization, Studies curation, Official studies, Funding purchase, Data, Methodology, Investment government, Information, Oversight, Visualization, Creating – brand new write, Writing – review & editing
Affiliations Corporal Michael Crescenz Va Medical facility, Philadelphia, Pennsylvania, U . s ., Department from Family genes, Perelman College or university out-of Medication, College or university out of Pennsylvania, Philadelphia, Pennsylvania, United states of america, Agencies off Systems Pharmacology and you may Translational Therapeutics, Perelman University regarding Treatments, College or university from Pennsylvania, Philadelphia, Pennsylvania, U . s ., Institute for Translational Treatments and Therapeutics, Perelman University out-of Drug, University off Pennsylvania, Philadelphia, Pennsylvania, Us
- Kelsey Age. Johnson,
- Katherine M. Siewert,
- Derek Klarin,
- Scott M. Damrauer,
- the new Va Mil Veteran Program,
- Kyong-Mi Chang,
- Philip S. Tsao,
- Themistocles L. Assimes,
- Kara Letter. Maxwell,
Record
A lot of epidemiological and you may hereditary research has attempted to determine if or not amounts of releasing lipids are associated with risks of some cancer tumors, plus cancer of the breast (BC). But not, they stays not sure if a beneficial causal citas sin gluten relationships is obtainable anywhere between lipids and BC. In the event the adjustment of lipid membership including shorter risk of BC, this may introduce an objective to possess situation reduction. This study aligned to assess a possible causal matchmaking anywhere between genetic variations regarding the plasma lipid qualities (high-density lipoprotein, HDL; low-occurrence lipoprotein, LDL; triglycerides, TGs) which have chance having BC using Mendelian randomization (MR).
Actions and findings
Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard–deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04–1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03–1.10, P = 4.9 ? 10 ?4 ) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01–1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06–1.16, P = 1.5 ? 10 ?6 ), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study.