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Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants: A mendelian randomization study.
Larsson, Susanna C; Carter, Paul; Vithayathil, Mathew; Mason, Amy M; Michaëlsson, Karl; Baron, John A; Burgess, Stephen.
Afiliação
  • Larsson SC; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: susanna.larsson@surgsci.uu.se.
  • Carter P; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Electronic address: paul_richard_carter@outlook.com.
  • Vithayathil M; MRC Cancer Unit, University of Cambridge, Cambridge, UK. Electronic address: mat2k89@gmail.com.
  • Mason AM; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, UK. Ele
  • Michaëlsson K; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: karl.michaelsson@surgsci.uu.se.
  • Baron JA; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Epide
  • Burgess S; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK. Electronic address: sb452@medschl.cam.ac.uk.
Clin Nutr ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33199044
ABSTRACT
BACKGROUND &

AIMS:

Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to pro-inflammatory eicosanoids, which according to experimental research modulate tumor cell proliferation, differentiation, and apoptosis. We employed the Mendelian randomization design to test the hypothesis that higher plasma phospholipid AA concentrations are associated with increased risk of 10 site-specific cancers.

METHODS:

Two genetic variants associated with plasma phospholipid concentrations of AA (rs174547 in FADS1 [P = 3.0 × 10-971] and rs16966952 in PDXDC1 [P = 2.4 × 10-10]) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium were used as genetic instruments. The associations of those variants with cancer were taken from the UK Biobank (n = 367,643), FinnGen consortium (n = 135,638), International Lung Cancer Consortium (n = 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n = 140,254), Breast Cancer Association Consortium (n = 228,951), Ovarian Cancer Association Consortium (n = 66,450), and BioBank Japan (n = 212,453).

RESULTS:

Higher genetically predicted plasma phospholipid AA concentrations were associated with increased risk of colorectal and lung cancer. Results were consistent across data sources and variants. The combined odds ratios per standard deviation increase of AA concentrations were 1.08 (95% CI 1.05-1.11; P = 6.3 × 10-8) for colorectal cancer and 1.07 (95%CI 1.05-1.10; P = 3.5 × 10-7) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02-1.17; P = 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary.

CONCLUSION:

These results indicate that AA may be implicated in the development of colorectal and lung cancer and possibly esophageal cancer. Treatments with plasma AA-lowering properties should be evaluated for clinical benefit.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico / Fatores de risco Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Artigo

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo prognóstico / Fatores de risco Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Artigo
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