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N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies.

ABSTRACT: Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86-0.98) compared to low blood levels of n-6 PUFAs. In the subgroup analyses by cancer site, type of n-6 PUFAs, and sex, the inverse associations were strong for breast cancer (RR = 0.87; 95% CI: 0.77-0.98), linoleic acid (LA) (RR = 0.91; 95% CI: 0.82-1.00), and women (RR = 0.88; 95% CI: 0.79-0.97). In the dose-response analysis, a 2% and 3% decrease in the risk of cancer was observed with a 5% increase in blood levels of n-6 PUFAs and LA, respectively. Thus, there was no significant association between n-6 PUFA intake and the risk of cancer. The pooled RR of cancer for the highest versus lowest category of n-6 PUFA intake was 1.02 (95% CI: 0.99-1.05). Evidence from prospective studies indicated that intake of n-6 PUFAs was not significantly associated with risk of cancer, but blood levels of n-6 PUFAs were inversely associated with risk of cancer.

SUBMITTER: Kim Y

PROVIDER: S-EPMC7551408 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies.

Kim Youngyo Y Kim Jeongseon J

Nutrients 20200820 9

Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86-0.98) compared t ...[more]

PMID: 32825393

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Project description:Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk.Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined.Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and ?-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses.Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk.Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.

Project description:BackgroundThe causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain.MethodsUsing a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures.FindingsGenetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding.InterpretationThe PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease.FundingCancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973).

Dataset Information

N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies.

Publications

N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies.

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