{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T23:01:26Z","timestamp":1780268486817,"version":"3.54.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Suzhou \u201cScience and Education Revitalize Health\u201d Youth Science and Technology Project","award":["KJXW2023009"],"award-info":[{"award-number":["KJXW2023009"]}]},{"name":"First Affiliated Hospital of Soochow University BOXI Clinical Research Project","award":["BXLC012"],"award-info":[{"award-number":["BXLC012"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Surg Onc"],"DOI":"10.1186\/s12957-026-04360-0","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:48:53Z","timestamp":1776322133000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of interleukin-21 on HBV-related hepatocellular carcinoma, from the perspective of genetics"],"prefix":"10.1186","volume":"24","author":[{"given":"Xi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"4360_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209\u201349.","journal-title":"CA Cancer J Clin"},{"key":"4360_CR2","doi-asserted-by":"publisher","first-page":"445","DOI":"10.3748\/wjg.v7.i4.445","volume":"7","author":"ZY Tang","year":"2001","unstructured":"Tang ZY. Hepatocellular carcinoma\u2013cause, treatment and metastasis. World J Gastroenterol. 2001;7:445\u201354.","journal-title":"World J Gastroenterol"},{"key":"4360_CR3","first-page":"574","volume":"11","author":"ZZ Zhu","year":"2003","unstructured":"Zhu ZZ, Cong WM. [Roles of hepatitis B virus and hepatitis C virus in hepato-carcinogenesis]. Zhonghua Gan Zang Bing Za Zhi. 2003;11:574\u20136.","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"4360_CR4","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/(SICI)1097-0215(20000215)85:4<498::AID-IJC9>3.0.CO;2-F","volume":"85","author":"H Kuper","year":"2000","unstructured":"Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO, et al. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer. 2000;85:498\u2013502.","journal-title":"Int J Cancer"},{"key":"4360_CR5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/hep.510240108","volume":"24","author":"CJ Chen","year":"1996","unstructured":"Chen CJ, Wang LY, Lu SN, Wu MH, You SL, Zhang YJ, et al. Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma. Hepatology. 1996;24:38\u201342.","journal-title":"Hepatology"},{"key":"4360_CR6","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/0140-6736(92)91528-G","volume":"339","author":"RK Ross","year":"1992","unstructured":"Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet. 1992;339:943\u20136.","journal-title":"Lancet"},{"key":"4360_CR7","first-page":"3","volume":"3","author":"GS Qian","year":"1994","unstructured":"Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, Henderson BE, et al. A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People\u2019s Republic of China. Cancer Epidemiol Biomarkers Prev. 1994;3:3\u201310.","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"4360_CR8","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S1726-4901(09)70346-6","volume":"70","author":"CJ Liu","year":"2007","unstructured":"Liu CJ, Kao JH. Hepatitis B virus-related hepatocellular carcinoma: epidemiology and pathogenic role of viral factors. J Chin Med Assoc. 2007;70:141\u20135.","journal-title":"J Chin Med Assoc"},{"key":"4360_CR9","doi-asserted-by":"crossref","unstructured":"Jury E. EASL International Consensus Conference on Hepatitis B. 13\u201314 September, 2002: Geneva, Switzerland. Consensus statement (short version). J Hepatol 2003; 38:533\u2013540.","DOI":"10.1016\/S0168-8278(03)00083-7"},{"key":"4360_CR10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1056\/NEJMoa013215","volume":"347","author":"HI Yang","year":"2002","unstructured":"Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168\u201374.","journal-title":"N Engl J Med"},{"key":"4360_CR11","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3892\/br.2013.166","volume":"1","author":"F Gong","year":"2013","unstructured":"Gong F, Su Q, Pan YH, Huang X, Shen WH. The emerging role of interleukin-21 in allergic diseases (Review). Biomed Rep. 2013;1:837\u20139.","journal-title":"Biomed Rep"},{"key":"4360_CR12","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1126\/science.1176487","volume":"324","author":"LD Johnson","year":"2009","unstructured":"Johnson LD, Jameson SC. Immunology. A chronic need for IL-21. Science. 2009;324:1525\u20136.","journal-title":"Science"},{"key":"4360_CR13","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3892\/ol.2012.966","volume":"5","author":"XC Pan","year":"2013","unstructured":"Pan XC, Li L, Mao JJ, Yao W, Zheng JN, Liu M, et al. Synergistic effects of soluble PD-1 and IL-21 on antitumor immunity against H22 murine hepatocellular carcinoma. Oncol Lett. 2013;5:90\u20136.","journal-title":"Oncol Lett"},{"key":"4360_CR14","doi-asserted-by":"publisher","first-page":"351","DOI":"10.4161\/onci.19122","volume":"1","author":"C Stolfi","year":"2012","unstructured":"Stolfi C, Pallone F, Macdonald TT, Monteleone G. Interleukin-21 in cancer immunotherapy: Friend or foe? Oncoimmunology. 2012;1:351\u20134.","journal-title":"Oncoimmunology"},{"key":"4360_CR15","doi-asserted-by":"publisher","first-page":"R116","DOI":"10.1186\/ar3053","volume":"12","author":"JE Hollis-Moffatt","year":"2010","unstructured":"Hollis-Moffatt JE, Chen-Xu M, Topless R, Dalbeth N, Gow PJ, Harrison AA, et al. Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance. Arthritis Res Ther. 2010;12:R116.","journal-title":"Arthritis Res Ther"},{"key":"4360_CR16","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1007\/s10753-012-9497-7","volume":"35","author":"L Ding","year":"2012","unstructured":"Ding L, Wang S, Chen GM, Leng RX, Pan HF, Ye DQ. A single nucleotide polymorphism of IL-21 gene is associated with systemic lupus erythematosus in a Chinese population. Inflammation. 2012;35:1781\u20135.","journal-title":"Inflammation"},{"key":"4360_CR17","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3892\/etm.2014.1707","volume":"8","author":"H Zeng","year":"2014","unstructured":"Zeng H, Yan H, Zhang Z, Fang W, Ding R, Huang L, et al. Association between IL-21 gene rs907715 polymorphisms and Graves\u2019 disease in a Southern Chinese population. Exp Ther Med. 2014;8:213\u20138.","journal-title":"Exp Ther Med"},{"key":"4360_CR18","first-page":"19460","volume":"8","author":"L Liu","year":"2015","unstructured":"Liu L, Shi F, Li S, Liu X, Wei L, Zhang J, et al. IL-21 polymorphisms rs907715 and rs2221903 are associated with decreased non-small cell lung cancer susceptibility. Int J Clin Exp Med. 2015;8:19460\u20135.","journal-title":"Int J Clin Exp Med"},{"key":"4360_CR19","doi-asserted-by":"publisher","first-page":"4232","DOI":"10.3748\/wjg.v21.i14.4232","volume":"21","author":"JY Yao","year":"2015","unstructured":"Yao JY, Chao K, Li MR, Wu YQ, Zhong BH. Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population. World J Gastroenterol. 2015;21:4232\u20139.","journal-title":"World J Gastroenterol"},{"key":"4360_CR20","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.meegid.2014.08.021","volume":"27","author":"Q Peng","year":"2014","unstructured":"Peng Q, Li H, Lao X, Deng Y, Chen Z, Qin X, et al. Association of IL-2 polymorphisms and IL-2 serum levels with susceptibility to HBV-related hepatocellular carcinoma in a Chinese Zhuang population. Infect Genet Evol. 2014;27:375\u201381.","journal-title":"Infect Genet Evol"},{"key":"4360_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.meegid.2013.01.015","volume":"16","author":"Q Peng","year":"2013","unstructured":"Peng Q, Qin X, He Y, Chen Z, Deng Y, Li T, et al. Association of IL27 gene polymorphisms and HBV-related hepatocellular carcinoma risk in a Chinese population. Infect Genet Evol. 2013;16:1\u20134.","journal-title":"Infect Genet Evol"},{"key":"4360_CR22","first-page":"7","volume":"71","author":"RL Siegel","year":"2021","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7\u201333.","journal-title":"CA Cancer J Clin"}],"container-title":["World Journal of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12957-026-04360-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12957-026-04360-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12957-026-04360-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T22:37:25Z","timestamp":1780267045000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12957-026-04360-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4360"],"URL":"https:\/\/doi.org\/10.1186\/s12957-026-04360-0","relation":{},"ISSN":["1477-7819"],"issn-type":[{"value":"1477-7819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"3 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study has been approved by the Ethics Committee. Subjects in the two groups are all residents of Jiangsu Province, and there is no kinship between them. All subjects and their families are aware of this study and voluntarily sign informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All subjects and their families are aware of this study and voluntarily sign informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"235"}}