{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:53:44Z","timestamp":1761490424939,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T00:00:00Z","timestamp":1511827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium-infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and\/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.<\/jats:p>","DOI":"10.3390\/ijms18122560","type":"journal-article","created":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T11:23:50Z","timestamp":1511868230000},"page":"2560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Estrogen Metabolism-Associated CYP2D6 and IL6-174G\/C Polymorphisms in Schistosoma haematobium Infection"],"prefix":"10.3390","volume":"18","author":[{"given":"Rita","family":"Cardoso","sequence":"first","affiliation":[{"name":"Department of Health Promotion and Chronic Diseases, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal"}]},{"given":"Pedro","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6125-7000","authenticated-orcid":false,"given":"Paulo","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS\/UP), Universidade do Porto, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto, Portugal"}]},{"given":"Ana","family":"Machado","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS\/UP), Universidade do Porto, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR\/CIMAR), Universidade do Porto, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"given":"Andr\u00e9","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Santo Antonio Hospital\u2014Centro Hospitalar do Porto (CHP), Largo do Prof. Abel Salazar, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9637-6541","authenticated-orcid":false,"given":"Adriano","family":"Bordalo","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS\/UP), Universidade do Porto, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR\/CIMAR), Universidade do Porto, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3984","authenticated-orcid":false,"given":"Ruben","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Escola Superior de Sa\u00fade, Instituto Polit\u00e9cnico do Porto, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 400, 4200-079 Porto, Portugal"},{"name":"Unit of Metabolism, Nutrition and Endocrinology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o da Universidade do Porto (i3S), Rua Alfredo Allen, 4200-135 Porto, Portugal"}]},{"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"Unit of Metabolism, Nutrition and Endocrinology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o da Universidade do Porto (i3S), Rua Alfredo Allen, 4200-135 Porto, Portugal"},{"name":"Departamento de Biomedicina, Unidade de Bioqu\u00edmica, Faculdade de Medicina, Universidade do Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Joachim","family":"Richter","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine and International Health, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}]},{"given":"Helena","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Chronic Diseases, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal"},{"name":"Funda\u00e7\u00e3o Professor Ernesto Morais, Rua de Monsanto 512, 4250-288 Porto, Portugal"}]},{"given":"Monica","family":"Botelho","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Chronic Diseases, National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandre Herculano 321, 4000-055 Porto, Portugal"},{"name":"Unit of Metabolism, Nutrition and Endocrinology, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o da Universidade do Porto (i3S), Rua Alfredo Allen, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.pt.2015.03.005","article-title":"The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: The case of schistosomes","volume":"31","author":"Botelho","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4161\/viru.2.4.16734","article-title":"Targeting molecular signaling pathways of Schistosoma haemotobium infection in bladder cancer","volume":"2","author":"Botelho","year":"2011","journal-title":"Virulence"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Koslowski, N., Sombetzki, M., Loebermann, M., Engelmann, R., Grabow, N., \u00d6sterreicher, C.H., Trauner, M., Mueller-Hilke, B., and Reisinger, E.C. 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