Abstract
BackgroundObservational studies indicate that phospholipid fatty acids (FAs) have an impact on the etiology in cancers, but the results are conflicting. We aimed to investigate the causal association of phospholipid FAs with breast cancer and prostate cancer.MethodsFourteen single nucleotide polymorphisms (SNPs) were selected as instrumental variables to predict the level of 10 phospholipid FAs from Genome-wide association studies (GWAS). We obtained the summary statistics for the latest and largest GWAS datasets for breast cancer (113,789 controls and 133,384 cases) and prostate cancer (61,106 controls and 79,148 cases) from the Breast Cancer Association Consortium (BCAC) and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Two-sample Mendelian randomization analysis was applied.ResultsThe results demonstrate that the 10 individual plasma phospholipid FAs are not significantly associated with breast cancer risk and prostate cancer risk.ConclusionThe evidence is insufficient to support the causal association of the 10 individual plasma phospholipid FAs with breast cancer and prostate cancer.
Highlights
Fatty acids (FAs) are involved in various physiological processes, including maintaining cell membrane stability, forming raft lipid to regulate signal transduction, the process of inflammation, and even hormone synthesis (Lands, 2014; Fritsche, 2015; Calder, 2020)
We used IVW method as primary analysis, the results of which show that the 10 individual FAs examined are not significantly associated with breast cancer: α-linolenic acid (ALA) (OR = 0.66, 95%Confidence interval (CI): 0.35, 1.24), Eicosapentaenoic acid (EPA) (OR = 1.07, 95%CI: 0.93, 1.23), Docosapentaenoic acid (DPA) (OR = 1.08, 95%CI: 0.94, 1.23), Docosahexaenoic acid (DHA) (OR = 1.01, 95%CI: 0.91, 1.13), linoleic acid (LA) (OR = 1.00, 95%CI: 0.99, 1.00), Arachidonic acid (AA) (OR = 1.00, 95%CI:1.00, 1.01), Palmitoleic acid (POA) (OR = 0.91, 95%CI: 0.63, 1.32), Oleic acid (OA) (OR = 0.97, 95%CI: 0.91, 1.02), Palmitic acid (PA) (OR = 1.03, 95%CI: 0.97, 1.11), Stearic acid (SA) (OR = 1.01, 95%CI: 0.97, 1.06) (Figure 2)
The results of IVW analysis demonstrate that the FAs are not causally associated with prostate cancer: ALA (OR = 0.87, 95%CI: 0.38, 1.99), EPA (OR = 1.12, 95%CI: 0.93, 1.36), DPA (OR = 1.10, 95%CI: 0.91, 1.32), DHA (OR = 0.89, 95%CI: 0.77, 1.03), LA (OR = 1.00, 95%CI: 0.98, 1.02), AA (OR = 1.00, 95%CI:0.98, 1.02), POA (OR = 0.88, 95%CI: 0.57, 1.35), OA (OR = 1.00, 95%CI: 0.93, 1.07), PA (OR = 1.01, 95%CI: 0.93, 1.11), SA (OR = 1.01, 95%CI: 0.95, 1.07) (Figure 3)
Summary
Fatty acids (FAs) are involved in various physiological processes, including maintaining cell membrane stability, forming raft lipid to regulate signal transduction, the process of inflammation, and even hormone synthesis (Lands, 2014; Fritsche, 2015; Calder, 2020). Several studies indicate that both the above FAs and monounsaturated fatty acids (MUFA) are not associated with breast cancer risk (Sanders, 2014; Cao et al, 2016; Zhou et al, 2016). These contradictory results are largely based on observational studies that are prone to reverse causality and residual confounding. A recent large randomized control trial (RCT, n = 25,871) with follow-up for an average of 5.3 years concluded that ω-3 PUFA supplementation did not reduce major cardiovascular events and overall cancer incidence (Manson et al, 2019), while the specific data of large RCT investigating the effects of PUFA, MUFA, and SFA on the two hormone-related cancer is limited. We aimed to investigate the causal association of phospholipid FAs with breast cancer and prostate cancer
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