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      Altered Red Blood Cell Membrane Fatty Acid Profile in Cancer Patients

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          Abstract

          The fatty acid (FA) composition of red blood cell (RBC) membrane phospholipids of cancer patients can reflect tumor status, dietary intakes, and cancer type or therapy. However, the characteristic membrane profiles have so far not yet defined as a potential biomarker to monitor disease evolution. The present work provides the first evidence of cancer metabolic signatures affecting cell membranes that are independent of nutritional habits. From the Oncology Outpatient Unit of the Onkologikoa hospital, two groups of cancer patients ( n = 54) and healthy controls ( n = 37) were recruited, and mature RBCs membrane phospholipids were analyzed for FA profiling (GC-MS). Dietary habits were evaluated using a validated food frequency questionnaire. The adjusted Analysis of Covariance Test (ANCOVA) model revealed cancer patients to have a lower relative percentage of saturated fatty acids (SFA) (C16:0 (5.7%); C18:0 (15.9%)), and higher monounsaturated fatty acids (MUFA) (9c-C18:1 (12.9%) and 11c-C18:1 (54.5%)), compared to controls. In line with this, we observe that the desaturase enzymatic index (delta-9 desaturase (Δ9D), +28.3%) and the membrane saturation index (SI = SFA/MUFA; −27.3%) were similarly modulated. Polyunsaturated fatty acids (PUFA) families showed an increase of n-6 C18:2 and C20:3 (15.7% and 22.2% respectively), with no differences in n-6 C20:4 and n-3 PUFA (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)). Importantly, these changes were found independent of foods and fat intakes from the diet. The membrane lipid profile in RBC was useful to ascertain the presence of two main metabolic signatures of increased desaturation activity and omega-6 in cancer patients, statistically independent from dietary habits.

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          Most cited references37

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          Adiposity and cancer at major anatomical sites: umbrella review of the literature

          Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer. Design Umbrella review of systematic reviews and meta-analyses. Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references. Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer. Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2 increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality. Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.
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            Comparison between plasma and erythrocyte fatty acid content as biomarkers of fatty acid intake in US women.

            Erythrocyte fatty acids may be superior to plasma fatty acids for reflecting long-term fatty acid intake because of less sensitivity to recent intake and a slower turnover rate. The objective was to compare the fatty acid content of erythrocytes with that of plasma with respect to their abilities to reflect usual fatty acid intake. Fatty acids in plasma and erythrocytes were measured by capillary gas-liquid chromatography in 306 US women aged 43-69 y. Fatty acid intake was assessed with a food-frequency questionnaire, which was validated for measuring intakes of various fatty acids. Docosahexaenoic acid (DHA, 22:6n-3) in erythrocytes and plasma provided the strongest correlations with its intake, but erythrocyte DHA concentrations [Spearman's partial correlation coefficient (r(s))=0.56] were better than plasma DHA concentrations (r(s)=0.48) as a biomarker. Total trans fatty acids (r(s)=0.43) and total 18:1 trans isomers (r(s)=0.42) in erythrocytes were also more strongly correlated with intake than were those in plasma (r(s)=0.30 and r(s)=0.29, respectively). Moderate correlations were observed for linoleic acid (18:2n-6; erythrocytes, r(s)=0.24; plasma, r(s)=0.25), alpha-linolenic acid (18:3n-3; erythrocytes, r(s)=0.18; plasma, r(s)=0.23), and eicosapentaenoic acid (20:5 n-3; erythrocytes, r(s)=0.38; plasma, r(s)=0.21). For polyunsaturated and trans fatty acids, correlations between intakes and biomarkers improved moderately when average intakes over previous years were used. Erythrocyte n-3 fatty acids of marine origin and trans fatty acid content are suitable biomarkers for long-term intake.
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              Metabolism of glycerolipides; a comparison of lecithin and triglyceride synthesis.

              W E Lands (1958)
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                01 December 2018
                December 2018
                : 10
                : 12
                : 1853
                Affiliations
                [1 ]AZTI, Food and Health, Parque Tecnológico de Bizkaia, Astondo Bidea, 609, 48160 Derio, Bizkaia, Spain; jamezaga@ 123456azti.es (J.A.); sarranz@ 123456azti.es (S.A.); mauriarte@ 123456azti.es (M.U.)
                [2 ]Onkologikoa Foundation, Paseo Doctor Begiristain, 121, 20014 San Sebastián, Gipuzkoa, Spain; anderu@ 123456onkologikoa.org (A.U.); gugartemendia@ 123456onkologikoa.org (G.U.); alarraioz@ 123456onkologikoa.org (A.L.)
                [3 ]Lipinutragen, Via di Corticella, 181/4, 40128 Bologna, Italy; maria.louka@ 123456lipinutragen.it
                [4 ]ISOF, Consiglio Nazionale delle Ricerche, Via Piero Gobetti, 101, 40129 Bologna, Italy
                Author notes
                [* ]Correspondence: carla.ferreri@ 123456isof.cnr.it (C.F.); itueros@ 123456azti.es (I.T.); Tel.: +39 051 639 8289 (C.F.); +34-667 174 290 (I.T.)
                Author information
                https://orcid.org/0000-0003-1829-111X
                https://orcid.org/0000-0002-7008-2406
                https://orcid.org/0000-0002-1359-0869
                https://orcid.org/0000-0002-7609-5435
                Article
                nutrients-10-01853
                10.3390/nu10121853
                6315925
                30513730
                ddecd3f4-6a87-41cd-97c5-09631abb5ffc
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 August 2018
                : 26 November 2018
                Categories
                Article

                Nutrition & Dietetics
                cancer,membrane lipidome,red blood cell,unsaturated fatty acids,saturation index,desaturase index

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