{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:48:17Z","timestamp":1776919697165,"version":"3.51.2"},"reference-count":115,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Cervical cancer (CC) is the fourth most common cancer diagnosis in women worldwide. Infection with high-risk human papillomavirus (HPV) is a critical but not determinative condition for CC development, as several co-factors modulate the progression of HPV-associated cervical lesions. Interleukin-8 (IL-8) and Interleukin-16 (IL-16) are chemokine-like interleukins involved in the pathogenesis of various cancers. Singular studies in Asian populations have suggested a potential role of IL-8 rs4073 (\u2212251 A&gt;T) and IL-16 rs1131445 (3\u2032UTR T&gt;C) in cervical carcinogenesis. Methods: A case-control study was conducted in a European cohort of 339 women, including 126 CC patients and 213 controls. Four common IL-8 SNPs, rs4073 (\u2212251 A&gt;T), rs2227306 (+781 C&gt;T), rs1126647 (+2767 A&gt;T), and rs2227543 (+1633 C&gt;T), and four IL-16 polymorphism, rs4778889 (\u2212295 T&gt;C), rs11556218 (3441 T&gt;G), rs4072111 (1300 C&gt;T), and rs1131445 (3\u2032UTR T&gt;C), were assessed using RFLP-PCR and analyzed under seven inheritance models. Subgroup analyses were stratified by menopausal status (age threshold 51 years), disease stage, and histological subtype. Results: IL-16 rs4072111 was significantly associated with an increased CC risk in premenopausal women in the co-dominant (p = 0.038), dominant (p = 0.022), and heterozygote (p = 0.045) models, identifying the T allele as the risk allele (OR 2.31, CI95% 1.17\u20134.56; p = 0.017). In women aged over 51, IL-16 rs4778889 was associated with CC in the heterozygote (p = 0.048) and overdominant (p = 0.042) models but not in the co-dominant model (p = 0.092). None of the analyzed SNPs significantly increased CC risk in the entire cohort. Specifically, neither IL-16 rs1131445 nor IL-8 rs4073, previously reported as risk factors in Asian populations, were associated with CC risk in this European cohort. Conclusions: These findings highlight the role of age stage in immunity and cancer susceptibility, suggest that IL-8 and IL-16 SNPs may function differently in cervical carcinogenesis compared with other cancers, and emphasize the importance of ethnic background in cancer risk, warranting further research.<\/jats:p>","DOI":"10.3390\/life15020135","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T04:19:51Z","timestamp":1737433191000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic Variants of Interleukin-8 and Interleukin-16 and Their Association with Cervical Cancer Risk"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-1887","authenticated-orcid":false,"given":"Rafa\u0142","family":"Watrowski","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Helios Hospital Muellheim, Teaching Hospital of the University of Freiburg, Heliosweg 1, 79379 Muellheim, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Schuster","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Polterauer","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2564-721X","authenticated-orcid":false,"given":"Toon","family":"Van Gorp","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, University Hospital Leuven, 3000 Leuven, Belgium"},{"name":"Leuven Cancer Institute, Catholic University of Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerda","family":"Hofstetter","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"},{"name":"Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, Dr.-Karl-Dorrek-Stra\u00dfe 30, 3500 Krems, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Mahner","sequence":"additional","affiliation":[{"name":"Department of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6771-4591","authenticated-orcid":false,"given":"Robert","family":"Zeillinger","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-2961","authenticated-orcid":false,"given":"Eva","family":"Obermayr","sequence":"additional","affiliation":[{"name":"Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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. 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