{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:37:59Z","timestamp":1782970679939,"version":"3.54.5"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Alterations in lipid metabolism are common in breast cancer (BRC) survivors on aromatase inhibitor therapy, and may increase the risk of cardiovascular complications. Long-chain n-3 and n-6 plasma fatty acids (PUFA) are substantial components of complex lipids, with important structural and regulatory functions. Their circulating levels are determined by both dietary intake and endogenous metabolism, of which the latter is influenced by polymorphisms in fatty acid desaturase (\n                      <jats:italic>FADS<\/jats:italic>\n                      ) genes. This study aimed to assess the association of\n                      <jats:italic>FADS<\/jats:italic>\n                      polymorphisms and plasma n-3 and n-6 PUFA levels in BRC survivors on AI therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fatty acid status was determined by gas chromatography, and\n                      <jats:italic>FADS<\/jats:italic>\n                      polymorphisms (rs174537, rs174576 and rs174602) were genotyped using real-time PCR. Dietary intake of n-3 and n-6 fatty acids was evaluated via three 24-h dietary recalls. Data were analyzed using a multiple linear regression model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All three polymorphisms were significantly associated with plasma arachidonic acid levels. Minor alleles of rs174537 (TT), rs174576 (AA) and rs174602 (CC) were associated with lower plasma arachidonic acid proportions. Moreover, positive association of rs174537 and rs174576 minor alleles with higher levels of linoleic acid, precursor of arachidonic acid and decreased estimated activities of delta-5 and delta-6 desaturases were observed, pointing out a lower conversion rate along the n-6 pathway. Lower levels of n-3 docosapentaenoic acid were associated with minor allele carriers of rs174576, while no significant differences were found for other n-3 PUFA. Dietary intake of n-3 and n-6 fatty acids did not differ significantly across the three genotypes, except for EPA for the rs174602 groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that\n                      <jats:italic>FADS<\/jats:italic>\n                      genotypes significantly influence plasma PUFA profiles independently of dietary intake in BRC survivors receiving AI therapy. This supports the potential relevance of considering genetic variability in future approaches aimed at optimizing PUFA balance and reducing CVD risk in this vulnerable population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1850476","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:25:21Z","timestamp":1782966321000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["FADS genotypes shape plasma polyunsaturated fatty acids independently of dietary intake in breast cancer survivors on aromatase inhibitors"],"prefix":"10.3389","volume":"13","author":[{"given":"Biljana","family":"Pokimica","sequence":"first","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]},{"name":"Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Vucic","sequence":"additional","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]},{"name":"Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snjezana","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]},{"name":"Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonida","family":"Bobic","sequence":"additional","affiliation":[{"name":"Clinic of Medical Oncology, Institute of Oncology and Radiology of Serbia","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Djurisic","sequence":"additional","affiliation":[{"name":"Department of Digestive Surgery, Institute of Oncology and Radiology of Serbia","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andjelija","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Milosevic","sequence":"additional","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.3390\/jcm13061818","article-title":"Aromatase inhibitors and plasma lipid changes in postmenopausal women with breast cancer: a systematic review and meta-analysis","volume":"13","author":"B\u00e9rczi","year":"2024","journal-title":"J Clin Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/978-3-319-70178-3_12","article-title":"Role of estrogens in the regulation of liver lipid metabolism","volume":"1043","author":"Palmisano","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"ref4","first-page":"785","article-title":"Genetic variants in the metabolism of omega-6 and omega-3 fatty acids: their role in the determination of nutritional requirements and chronic disease risk","volume-title":"Exp Biol Med (Maywood)","author":"Simopoulos","year":"2010"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.lfs.2018.04.049","article-title":"Omega-3 and omega-6 polyunsaturated fatty acids: dietary sources, metabolism, and significance \u2014 a review","volume":"203","author":"Saini","year":"2018","journal-title":"Life Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"965","DOI":"10.3390\/nu2090965","article-title":"Long-chain polyunsaturated fatty acids in inborn errors of metabolism","volume":"2","author":"Fekete","year":"2010","journal-title":"Nutrients"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"15873","DOI":"10.1038\/s41598-020-71948-1","article-title":"FADS genetic and metabolomic analyses identify the \u03945 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids","volume":"10","author":"Reynolds","year":"2020","journal-title":"Sci Rep"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1111624","DOI":"10.3389\/fnut.2023.1111624","article-title":"Impact of FADS gene variation and dietary fatty acid exposure on biochemical and anthropomorphic phenotypes in a Hispanic\/Latino cohort","volume":"10","author":"Sergeant","year":"2023","journal-title":"Front Nutr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1080\/00325481.2019.1607414","article-title":"The eicosapentaenoic acid:arachidonic acid ratio and its clinical utility in cardiovascular disease","volume":"131","author":"Nelson","year":"2019","journal-title":"Postgrad Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.atherosclerosis.2013.09.023","article-title":"Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: the Hisayama study","volume":"231","author":"Ninomiya","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1001\/jamacardio.2020.0246","article-title":"Association of FADS1\/2 locus variants and polyunsaturated fatty acids with aortic stenosis","volume":"5","author":"Chen","year":"2020","journal-title":"JAMA Cardiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.3390\/nu11123001","article-title":"Plasma phospholipid fatty acids, FADS1 and risk of 15 cardiovascular diseases: a Mendelian randomisation study","volume":"11","author":"Yuan","year":"2019","journal-title":"Nutrients"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"102155","DOI":"10.1016\/j.plefa.2020.102155","article-title":"Metabolic syndrome in postmenopausal women is associated with lower erythrocyte PUFA\/MUFA and n-3\/n-6 ratio: a case-control study","volume":"159","author":"Muzsik","year":"2020","journal-title":"Prostaglandins Leukot Essent Fat Acids"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12986-015-0010-9","article-title":"Ethnicity, sex, FADS genetic variation, and hormonal contraceptive use influence delta-5- and delta-6-desaturase indices and plasma docosahexaenoic acid concentration in young Canadian adults: a cross-sectional study","volume":"12","author":"Abdelmagid","year":"2015","journal-title":"Nutr Metab (Lond)"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.nutres.2020.08.010","article-title":"FADS2 polymorphisms are associated with plasma arachidonic acid and estimated desaturase-5 activity in a cross-sectional study","volume":"83","author":"Zec","year":"2020","journal-title":"Nutr Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"296","DOI":"10.3390\/nu13020296","article-title":"Is there a FADS2-modulated link between long-chain polyunsaturated fatty acids in plasma phospholipids and polyphenol intake in adult subjects who are overweight?","volume":"13","author":"Zec","year":"2021","journal-title":"Nutrients"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.3390\/cancers17132154","article-title":"Preliminary insights into quality of life and dietary intake in patients with breast cancer on adjuvant endocrine therapy","volume":"17","author":"Petrovic","year":"2025","journal-title":"Cancers (Basel)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1038\/sj.bjc.6605441","article-title":"Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial","volume":"101","author":"Bougnoux","year":"2009","journal-title":"Br J Cancer"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"892","DOI":"10.3389\/fphys.2019.00892","article-title":"Hydroxymethylglutaryl coenzyme a reductase inhibitors differentially modulate plasma fatty acids in rats with diet-induced hyperhomocysteinemia: is \u03c9-3 fatty acids supplementation necessary?","volume":"10","author":"Nikolic Turnic","year":"2019","journal-title":"Front Physiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1101\/gr.137323.112","article-title":"Annotation of functional variation in personal genomes using RegulomeDB","volume":"22","author":"Boyle","year":"2012","journal-title":"Genome Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12967-016-0834-8","article-title":"Polymorphisms in FADS1 and FADS2 alter plasma fatty acids and desaturase levels in type 2 diabetic patients with coronary artery disease","volume":"14","author":"Li","year":"2016","journal-title":"J Transl Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"4867","DOI":"10.3390\/ijms2610486723","article-title":"Nutrigenetics and omega-3 and gamma-linolenic acid intake and status in patients with cancer: a PRISMA scoping review of research trends and challenges","volume":"26","author":"Zikic","year":"2025","journal-title":"Int J Mol Sci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.plefa.2013.12.006","article-title":"Effect of sex hormones on n-3 polyunsaturated fatty acid biosynthesis in HepG2 cells and in human primary hepatocytes","volume":"90","author":"Sibbons","year":"2014","journal-title":"Prostaglandins Leukot Essent Fat Acids"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.jpain.2014.01.487","article-title":"Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer","volume":"15","author":"Henry","year":"2014","journal-title":"J Pain"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12263-024-00747-4","article-title":"Genetic association between FADS and ELOVL polymorphisms and the circulating levels of EPA\/DHA in humans: a scoping review","volume":"19","author":"Loukil","year":"2024","journal-title":"Genes Nutr"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1002\/pros.23205","article-title":"Impact of genetic and epigenetic variations within the FADS cluster on the composition and metabolism of polyunsaturated fatty acids in prostate cancer","volume":"76","author":"Cui","year":"2016","journal-title":"Prostate"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1850476\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:25:22Z","timestamp":1782966322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1850476\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":26,"alternative-id":["10.3389\/fnut.2026.1850476"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1850476","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1850476"}}