Mendelian Randomization Study for Genetically Predicted Polyunsaturated Fatty Acids Levels on Overall Cancer Risk and Mortality

Liyanage, Upekha E.; Ong, Jue‐Sheng; An, Jiyuan; Gharahkhani, Puya; Law, Matthew H.; MacGregor, Stuart

doi:10.1158/1055-9965.epi-18-0940

Cited by 19 publications

(22 citation statements)

References 58 publications

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“…Our results based on data from UK Biobank and the International Lung Cancer Consortium, FinnGen consortium, and BioBank Japan provide further support for an association between higher AA concentrations and increased risk of lung cancer. As in our study, no association was observed between genetically predicted AA concentrations and risk of breast, prostate, and pancreatic cancer in a previous MR study in UK Biobank participants [25]. We are not aware of any previous study of genetically predicted AA concentrations or FADS1 polymorphisms in relation to esophageal cancer, and MR studies of AA and other cancers are scarce.…”

Section: Discussioncontrasting

confidence: 61%

“…With regard to lung cancer, a previous study showed that a variant in the FADS1 gene (rs174548) was statistically significantly associated with lung cancer risk in 13,821 Europeans and 18,471 Asians [26]. In addition, genetically predicted AA concentrations (per SD increase) were associated with an OR of lung cancer of 1.08 (95% CI 1.00e1.16) in UK Biobank (1863 lung cancer cases) [25]. Our results based on data from UK Biobank and the International Lung Cancer Consortium, FinnGen consortium, and BioBank Japan provide further support for an association between higher AA concentrations and increased risk of lung cancer.…”

Section: Discussionmentioning

confidence: 98%

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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

et al. 2021

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Background & aims: Arachidonic acid (AA) is metabolized by cyclooxygenases and lipoxygenases to proinflammatory 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 ¼ 3.0 Â 10 À971 ] and rs16966952 in PDXDC1 [P ¼ 2.4 Â 10 À10 ]) 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 ¼ 367,643), FinnGen consortium (n ¼ 135,638), International Lung Cancer Consortium (n ¼ 27,209), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (n ¼ 140,254), Breast Cancer Association Consortium (n ¼ 228,951), Ovarian Cancer Association Consortium (n ¼ 66,450), and BioBank Japan (n ¼ 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 1.05e1.11; P ¼ 6.3 Â 10 À8) for colorectal cancer and 1.07 (95%CI 1.05e1.10; P ¼ 3.5 Â 10 À7) for lung cancer. Genetically predicted AA concentrations had a suggestive positive association with esophageal cancer (odds ratio 1.09; 95% CI 1.02e1.17; P ¼ 0.016) but were not associated with cancers of the stomach, pancreas, bladder, prostate, breast, uterus, or ovary.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 98%

Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants: A mendelian randomization study

et al. 2021

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“…After excluding duplicate papers (n=5991) and studies that did not meet the inclusion criteria (n=6829), 53 full articles of potentially relevant studies were assessed for eligibility ( fig 1 ). After full text reviews, eight articles were excluded for being conducted on patients who required haemodialysis (n=1) 70 or critically ill patients (n=1), 71 having a case-control design (n=1), 72 assessing genetically predicted ALA levels rather than tissue levels (n=1), 73 and not reporting relative risk estimates (n=1) or 95% confidence intervals (n=3). 74 75 76 In addition, two different publications were found for the Nurses’ Health Study, 34 77 three for the Health Professionals Follow-up Study, 34 78 79 and two for the Cardiovascular Health Study.…”

Section: Resultsmentioning

confidence: 99%

Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies

Naghshi

Aune

Beyene

et al. 2021

BMJ

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Objective To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer. Design Systematic review and meta-analysis of prospective cohort studies. Data sources PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021. Study selection Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer. Data synthesis Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality. Results 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I 2 =77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I 2 =48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I 2 =5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I 2 =3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I 2 =76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I 2 =30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I 2 =8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I 2 =37.1%, n=14). Conclusions The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only. Systematic review registration PROSPERO CRD42021229487.

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“…. Given 6 individual cancers were considered, we set a significance threshold of 0.004/36=0.0001.” 83 …”

Section: Methodsmentioning

confidence: 99%

Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration

Skrivankova

Richmond

Woolf

et al. 2021

BMJ

653

478

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In observational epidemiology, mendelian randomisation (MR) studies provide an opportunity to study the causal association between an exposure and an outcome while reducing the risk of certain biases Little consensus exists around the reporting of MR studies, and the quality of reporting of these studies has been inconsistent; many MR study reports do not state or examine the various assumptions of MR and report insufficient details on the data sources STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomisation), a checklist of 20 reporting items, has been developed for the communication of MR studies This article explains the rationale of these checklist items and provides examples of transparent reporting MR study authors, reviewers, and journal editors are encouraged to use STROBE-MR to improve the reporting of these studies on 3 November 2021 by guest. Protected by copyright.

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Mendelian Randomization Study for Genetically Predicted Polyunsaturated Fatty Acids Levels on Overall Cancer Risk and Mortality

Cited by 19 publications

References 58 publications

Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants: A mendelian randomization study

Genetically predicted plasma phospholipid arachidonic acid concentrations and 10 site-specific cancers in UK biobank and genetic consortia participants: A mendelian randomization study

Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies

Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration

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