{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:38:31Z","timestamp":1791661111819,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The reference interval (RI) for a tumor marker may vary between populations, detection systems, and the methods used to obtain their values. The aims of this study were to establish age\u2010 and sex\u2010specific RIs for the following nine common tumor markers and to validate the established RIs in Korean adults: alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)\u00a019\u20109, CA15\u20103, CA125, Human epididymis protein 4 (HE4), total prostate specific antigen, cytokeratin fragment (Cyfra) 21\u20101, and progastrin\u2010releasing peptide (ProGRP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross\u2010sectional study consecutively selected 214,159 individuals (aged 18\u201398 years) who underwent health checkups at 16 health\u2010promotion centers in 13 Korean cities. Finally, 62,752 examinees were used to establish the RIs after removing outliers. RIs were established using an indirect method according to the CLSI EP28\u2010A3C guideline. The established RIs were validated by calculating the proportion of individuals outside each RI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sex\u2010related differences were observed for AFP, CEA, CA19\u20109, Cyfra 21\u20101, and ProGRP (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05): AFP, CEA and Cyfra 21\u20101 were higher in males, and CA19\u20109 and proGRP were higher in females. Most of the tumor markers except CA15\u20103 and CA125 increased with age: CA125 decreased at \u226550 years of age (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), while CA15\u20103 did not vary with age. Less than 5% of subjects were outside all RIs (the 2.5th and 97.5th percentiles) established in the present study. Meanwhile, less than 3% of the healthy reference subjects fell outside the current and manufacturers' RIs of all tumor markers except Cyfra 21\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study has determined age\u2010 and sex\u2010specific RIs for nine common tumor markers in the healthy Korean population, which could be useful for clinicians making clinical decisions and assessments.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.1107","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T09:48:06Z","timestamp":1676108886000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Establishment and validation of reference intervals for tumor markers (AFP, CEA, CA19\u20109, CA15\u20103, CA125, PSA, HE4, Cyfra 21\u20101, and ProGRP) in primary care centers in Korea: A cross\u2010sectional retrospective study"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-4364","authenticated-orcid":false,"given":"Eun\u2010Hee","family":"Nah","sequence":"first","affiliation":[{"name":"Health Promotion Research Institute Korea Association of Health Promotion  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon","family":"Cho","sequence":"additional","affiliation":[{"name":"Health Promotion Research Institute Korea Association of Health Promotion  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeran","family":"Park","sequence":"additional","affiliation":[{"name":"Health Promotion Research Institute Korea Association of Health Promotion  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Health Promotion Research Institute Korea Association of Health Promotion  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunjoo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Health Promotion Research Institute Korea Association of Health Promotion  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Ik","family":"Cho","sequence":"additional","affiliation":[{"name":"MEDIcheck LAB Korea Association of Health Promotion  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"issue":"4","key":"e_1_2_12_2_1","first-page":"30","article-title":"The ecology of tumors: by perturbing the microenvironment, wounds and infection may be key to tumor development","volume":"20","author":"Kenny PA","year":"2006","journal-title":"Scientist (Philadelphia, Pa.)"},{"key":"e_1_2_12_3_1","article-title":"Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal \u201cunity of ecology and evolution: pathological ecosystem","author":"Luo W","year":"2022","journal-title":"Preprints"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2021.290"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/149014"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2006.12.001"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.5409"},{"issue":"6","key":"e_1_2_12_8_1","first-page":"1075","article-title":"Serum tumor markers","volume":"68","author":"Perkins GL","year":"2003","journal-title":"Am Fam Physician"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPN5BMTSF1CDYP"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000002915"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009734.2011.644873"},{"issue":"2","key":"e_1_2_12_12_1","first-page":"185","article-title":"Standardization of reference values among laboratories of Korean association of health promotion","volume":"24","author":"Lee KN","year":"2002","journal-title":"Lab Med Qual Assur"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3343\/kjlm.2008.28.3.179"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26129"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.7704\/kjhugr.2021.0058"},{"key":"e_1_2_12_16_1","first-page":"1","article-title":"User demonstration of performance for precision and accuracy; 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