The connection between dispersing lipids and you can cancer of the breast exposure: A beneficial Mendelian randomization studies
Associations Boston Va Medical care System, Boston, Massachusetts, United states, Cardiovascular system getting Genomic Medicine, Massachusetts General Medical, Harvard Scientific School, Boston, Massachusetts, Usa, System inside the Scientific and you will Society Family genes, Wider Institute out of MIT and you will Harvard, Cambridge, Massachusetts, Usa
Associations Corporal Michael Crescenz Virtual assistant Healthcare facility, Philadelphia, Pennsylvania, Us, Department off Surgery, Perelman School off Treatments, College or university out of Pennsylvania, Philadelphia, Pennsylvania, Usa
Associations Corporal Michael Crescenz Virtual assistant Medical facility, Philadelphia, Pennsylvania, Us, Agencies off Medicine, Perelman School off Drug, University regarding Pennsylvania, Philadelphia, Pennsylvania, United states
Associations Va Palo Alto Health care System, Palo Alto, California, Us, Service from Medication, Stanford University School out-of Medication, Stanford, Ca, U . s .
Associations Va Palo Alto Medical care System, Palo Alto, California, Us, Department out of Treatments, Stanford University School of Medicine, Stanford, Ca, U . s .
Associations Department out-of Medication, Perelman University off Drug, College or university away from Pennsylvania, Philadelphia, Pennsylvania, Us, Institution from Genetics, Perelman College or university from Treatments, College or university out of Pennsylvania, Philadelphia, Pennsylvania, United states of america
Positions Conceptualization, Data curation, Official studies, Money acquisition, Research, Strategy, Venture administration, Resources, Oversight, Visualization, Writing – fresh write, Writing – comment & editing
Affiliations Corporal Michael Crescenz Va Medical center, Philadelphia, Pennsylvania, United states, Company away from Genetics, Perelman School of Medicine, University regarding Pennsylvania, Philadelphia, Pennsylvania, United states, Company away from Assistance Pharmacology and you may Translational Therapeutics, Perelman University regarding Treatments, College or university out-of Pennsylvania, Philadelphia, Pennsylvania, Us, Institute getting Translational Medication and you will Therapeutics, Perelman School of Drug, University regarding Pennsylvania, Philadelphia, Pennsylvania, United states
- Kelsey Age. Johnson,
- Katherine Yards. Siewert,
- Derek Klarin,
- Scott Meters. Damrauer,
- the fresh new Va Million Seasoned Program,
- Kyong-Mi Chang,
- Philip S. Tsao,
- Themistocles L. Assimes,
- Kara N. Maxwell,
Records
A great amount of epidemiological and hereditary research has made an effort to determine if or not amounts of dispersing lipids are associated with the dangers of certain cancer, and additionally breast cancer (BC). However, it remains undecided whether or not an effective causal relationship is obtainable ranging from lipids and you will BC. In the event that customization out-of lipid membership in addition to shorter threat of BC, this could introduce a target to have condition avoidance. This research aimed to assess a prospective causal dating BDSM-Dating-Seiten in den USA ranging from hereditary variants for the plasma lipid attributes (high-thickness lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with exposure to possess BC using Mendelian randomization (MR).
Steps and you may 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.