The relationship ranging from distributing lipids and you may breast cancer risk: Good Mendelian randomization study

The relationship ranging from distributing lipids and you may breast cancer risk: Good Mendelian randomization study

Associations Boston Va Medical care System, Boston, Massachusetts, Usa, Center for Genomic Medicine, Massachusetts General Healthcare, Harvard Medical College, Boston, Massachusetts, United states, System for the Medical and you can Society Genetics, Wider Institute away from MIT and you can Harvard, Cambridge, Massachusetts, U . s .

Affiliations Corporal Michael Crescenz Virtual assistant Hospital, Philadelphia, Pennsylvania, https://datingranking.net/fr/brancher/ United states of america, Agencies away from Procedures, Perelman College away from Medicine, School of Pennsylvania, Philadelphia, Pennsylvania, United states

Associations Corporal Michael Crescenz Virtual assistant Medical, Philadelphia, Pennsylvania, United states, Agency out of Medication, Perelman College or university out-of Treatments, University regarding Pennsylvania, Philadelphia, Pennsylvania, Usa

Associations Va Palo Alto Healthcare Program, Palo Alto, California, United states, Department regarding Medication, Stanford College College out of Medicine, Stanford, Ca, Usa

Associations Virtual assistant Palo Alto Health care System, Palo Alto, Ca, Usa, Agencies out of Medication, Stanford College or university College or university from Drug, Stanford, California, Usa

Affiliations Service of Drug, Perelman University out of Drug, University regarding Pennsylvania, Philadelphia, Pennsylvania, Us, Agency from Genetics, Perelman University away from Medicine, University away from Pennsylvania, Philadelphia, Pennsylvania, United states

Roles Conceptualization, Studies curation, Certified study, Financial support order, Studies, Strategy, Investment administration, Resources, Supervision, Visualization, Creating – fresh write, Composing – feedback & modifying

Associations Corporal Michael Crescenz Va Medical center, Philadelphia, Pennsylvania, United states, Company away from Family genes, Perelman University away from Medication, College regarding Pennsylvania, Philadelphia, Pennsylvania, United states of america, Institution out-of Possibilities Pharmacology and you will Translational Therapeutics, Perelman School regarding Treatments, School off Pennsylvania, Philadelphia, Pennsylvania, United states, Institute to own Translational Medicine and you may Therapeutics, Perelman College regarding Medicine, School of Pennsylvania, Philadelphia, Pennsylvania, United states of america

  • Kelsey Elizabeth. Johnson,
  • Katherine M. Siewert,
  • Derek Klarin,
  • Scott Meters. Damrauer,
  • the fresh new Va Mil Seasoned System,
  • Kyong-Mi Chang,
  • Philip S. Tsao,
  • Themistocles L. Assimes,
  • Kara Letter. Maxwell,

History

A good amount of epidemiological and you can genetic research has made an effort to dictate if or not amounts of distributing lipids is on the risks of some cancer tumors, including cancer of the breast (BC). not, they stays undecided if good causal matchmaking is obtainable anywhere between lipids and BC. When the alteration regarding lipid membership along with quicker danger of BC, this might present a target to have disease prevention. This research lined up to evaluate a possible causal relationship between hereditary variations for the plasma lipid attributes (high-occurrence lipoprotein, HDL; low-occurrence lipoprotein, LDL; triglycerides, TGs) having exposure to own BC having fun with Mendelian randomization (MR).

Methods and you will conclusions

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.

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