Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials

Hanson, Sarah; Thorpe, Gabrielle; Winstanley, L.; Abdelhamid, Asmaa; Hooper, Lee

doi:10.1038/s41416-020-0761-6

Cited by 81 publications

(68 citation statements)

References 43 publications

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“…Essential fatty acids, including linoleic and LC n–3 fatty acids, must be obtained from the diet as they are not endogenously synthesized. The relation between the status of these fatty acids and breast cancer risk continues to be unclear ( 64 ). Statistical interactions for linoleic acid, ALA, and total LC n–3 suggested inverse associations in postmenopausal women compared with premenopausal women in ATP.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Analysis of Plasma Phospholipid Fatty Acids and Breast Cancer Risk in 2 Provinces in Canada

Newell

Ghosh

Goruk

et al. 2021

Current Developments in Nutrition

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Background Studies suggest that fatty acid status influences breast cancer etiology, yet the roles of individual fatty acids in breast cancer risk are unclear, specifically when central adiposity and menopausal status are considered. Objectives This study examined the associations of fatty acid status with breast cancer risk including location, menopausal status and waist-to-hip ratio as key variables. Methods Pre-diagnostic plasma phospholipid fatty acids were measured in women with breast cancer (n = 393) and age-matched controls (n = 786) from a nested case-control prospective study within Alberta's Tomorrow Project (ATP) and British Columbia Generations Project (BCGP) cohorts. Binary logistic regression models were used to evaluate associations of fatty acids and breast cancer risk with subgroup analysis for menopausal status and waist-to-hip ratio. Results Women from BCGP had a higher n-3 fatty acid status compared to ATP (6.4 ± 0.08% vs. 5.3 ± 0.06%, P < 0.001) so subsequent analysis was blocked by cohort. Overall, fatty acids had inconsistent associations with risk. In ATP among premenopausal women, total long chain n-3 fatty acids (ORQ4vsQ1 = 1.78; 95% CI, 0.58–5.43, Ptrend = 0.007, Pint = 0.07) were positively associated with breast cancer risk whereas in BCGP, docosahexaenoic acid (ORQ4vsQ1 = 0.66; 95% CI, 0.28–1.53, Ptrend = 0.03, Pint = 0.05) and total long chain n-3 (ORQ4vsQ1 = 0.66; 95% CI, 0.28–1.54, Ptrend = 0.03) were associated with decreased cancer risk when the waist-to-hip ratio was < 0.85. Conclusions Our findings suggest that regional variations in fatty acid status influence breast cancer risk, resulting in positive associations of total long chain n-3 fatty acids in premenopausal ATP women and negative associations of these fatty acids in BCGP women with a waist-to-hip ratio below guidelines. This study highlights the complexity and difficulty in using fatty acid status to predict breast cancer risk in diverse populations without the consideration of other risk factors.

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Section: Discussionmentioning

confidence: 99%

A Prospective Analysis of Plasma Phospholipid Fatty Acids and Breast Cancer Risk in 2 Provinces in Canada

Newell

Ghosh

Goruk

et al. 2021

Current Developments in Nutrition

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“…Notably, high expression of the GCNT1 has been previously reported in multiple cancers, including in prostate cancer [ 51 – 55 ]. Consumption of omega-6 fatty acids has been shown to increase risk of developing prostate cancer from randomized trials [ 56 ], human cell experiment [ 57 ], and mice model [ 58 ]. Two other genes that were found in this study to interact in association with GCNT1 are SCN2B and SCN4B , components of voltage-gated sodium channels, and both of these factors have been previously associated with the developing prostate cancer [ 59 , 60 ] and promoting cancer metastasis [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of gene-gene interactions in cardiac traits and serum fatty acid levels in the LURIC Health Study

et al. 2020

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Epistasis analysis elucidates the effects of gene-gene interactions (G×G) between multiple loci for complex traits. However, the large computational demands and the high multiple testing burden impede their discoveries. Here, we illustrate the utilization of two methods, main effect filtering based on individual GWAS results and biological knowledge-based modeling through Biofilter software, to reduce the number of interactions tested among single nucleotide polymorphisms (SNPs) for 15 cardiac-related traits and 14 fatty acids. We performed interaction analyses using the two filtering methods, adjusting for age, sex, body mass index (BMI), waist-hip ratio, and the first three principal components from genetic data, among 2,824 samples from the Ludwigshafen Risk and Cardiovascular (LURIC) Health Study. Using Biofilter, one interaction nearly met Bonferroni significance: an interaction between rs7735781 in XRCC4 and rs10804247 in XRCC5 was identified for venous thrombosis with a Bonferroni-adjusted likelihood ratio test (LRT) p: 0.0627. A total of 57 interactions were identified from main effect filtering for the cardiac traits G×G (10) and fatty acids G×G (47) at Bonferroni-adjusted LRT p < 0.05. For cardiac traits, the top interaction involved SNPs rs1383819 in SNTG1 and rs1493939 (138kb from 5' of SAMD12) with Bonferroni-adjusted LRT p: 0.0228 which was significantly associated with history of arterial hypertension. For fatty acids, the top interaction between rs4839193 in KCND3 and rs10829717 in LOC107984002 with Bonferroni-adjusted LRT p: 2.28×10 −5 was associated with 9-trans 12-trans octadecanoic acid, an omega-6 trans fatty acid. The model inflation factor for the interactions under different filtering methods was evaluated from the standard median and the linear regression approach. Here, we applied filtering approaches to identify numerous genetic interactions related to cardiac-related outcomes as potential targets for therapy. The

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“…This systematic review and meta-analysis is part of a series of systematic reviews commissioned by the World Health Organization (WHO) assessing health effects of omega-3, omega-6 and total PUFA. [15][16][17][18][19][20][21][22][23] Its protocol was registered (International Prospective Register of Systematic Reviews identifier: CRD42017056092). Specific methods for this review are discussed below, and detailed methods for the review series are reported elsewhere, including detailed search strategies, list of variables data extracted and the wider database of trials.…”

Section: Methodsmentioning

confidence: 99%

“…We assessed Cochrane risk-of-bias domains, 25 and also assessed risk from adherence problems and attention bias specifically for our reviews. [15][16][17][18][19][20][21][22][23] Included trials were judged at low summary risk of bias where randomisation, allocation concealment, blinding of participants, personnel and outcome assessors were adequate (all other trials were at moderate or high risk of bias).…”

Section: Assessment Of Risk Of Bias In Included Studiesmentioning

confidence: 99%

“…We have formally systematically reviewed effects of omega-3, omega-6 and total PUFA on cancer, diabetes, cognition, inflammatory bowel disease, cardiovascular disease, functional outcomes, mortality, adiposity and lipids in sister reviews, so these outcomes are not reported here. [15][16][17][18][19][20][21][22][23] Discussion GRADE assessment of our meta-analytic data suggests that increasing LCn3 probably has little or no effect on risk of depression or anxiety symptoms in those without depression or anxiety at baseline (moderate-quality evidence), but effects on depression severity and risk of remission in depression were unclear. Increasing ALA may increase risk of depression symptoms very slightly (1000 people would need to increase their ALA intake for one additional 10.7 3.5 Fig.…”

Section: Secondary Outcomesmentioning

confidence: 99%

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Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials

et al. 2019

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BackgroundThere is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety.AimsTo assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms.MethodWe searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment.ResultsWe included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92–1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05–0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000).ConclusionsLong-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.Declaration of interestL.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.

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Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials

Cited by 81 publications

References 43 publications

A Prospective Analysis of Plasma Phospholipid Fatty Acids and Breast Cancer Risk in 2 Provinces in Canada

A Prospective Analysis of Plasma Phospholipid Fatty Acids and Breast Cancer Risk in 2 Provinces in Canada

Investigation of gene-gene interactions in cardiac traits and serum fatty acid levels in the LURIC Health Study

Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials

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