Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population

Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population ahlem helaoui, Sana Sfar, Najet Boudhiba, Fariba Dehghanian, Moein Dehbashi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1540515/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Host genetic characteristics and environmental factors interactions may play a crucial role in cervical carcinogenesis. We investigated the impact of functional genetic variants of four xenobiotic-metabolizing genes (AhR, CYP1A1, GSTM1, and GSTT1) on cervical cancer development in Tunisian women. Methods: The AhR gene polymorphism was analyzed using the tetra-primer ARMS-PCR, whereas the CYP1A1 polymorphism genotypes were identified by PCR-RFLP. A multiplex ligation-dependent polymerase chain reaction approach was applied for the analysis of GSTM1 and GSTT1 polymorphisms. Results: The homozygous A/A genotype of the AhR gene (rs2066853) and the heterozygous T/C genotype of the CYP1A1 SNP (CYP1A1-MspI) appeared to be associated with an increased risk of cervical tumorigenesis (ORa = 2.81; ORa = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (ORa = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (ORa = 1.18; p = 0.784). Considering the combined effect, we noted a significantly higher association with cancer risk for individuals with at least two high-risk genotypes of CYP1A1/GSTT1 (ORa = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (ORa = 11.3) and individuals with at least two high-risk genotypes of CYP1A1/GSTM1/GSTT1/AhR exploitation low-risk genotype as a reference. Conclusion: This study indicated that the single-gene contribution and the combined effect of xenobioticmetabolizing gene polymorphisms (AhR, CYP1A1-MspI, GSTM1, and GSTT1) may have a considerable association with increased cervical cancer risk. Cervical cancer Xenobiotic-metabolizing genes AhR CYP1A1 GSTM1 and GSTT1. Full Text Tables Tables 1 to 4 are available in the Supplementary Files section. Supplementary Files TablelegendsAhlemHELAOUI.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 08 Jun, 2022 Reviews received at journal 27 Apr, 2022 Reviewers invited by journal 13 Apr, 2022 Editor assigned by journal 12 Apr, 2022 First submitted to journal 09 Apr, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1540515","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":98373041,"identity":"fd7d78e1-79ee-4c0d-8f51-85297862f365","order_by":0,"name":"ahlem helaoui","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYBACNgnmBiB1mIEPxEuokGAwIKSFX4IRooUNrOUMQosELi2SM5C1MLYxENZicLux8dENhsNybOyHj0k8nGdhby52gO1zYRtDnTkuLXcONhvnMPw3ZuNJS5NI3CaRuHN2AvPsmW0MEpYNOLTcSGyTzmE4nNjGkGMG0pJgcDuBmZkXqMXgAHYt9jcS238DtdS38b8BapkjYU9QC8gWZqCWBDYJkC0NEowbiNDSLJ1jcNiwTeJZskXCMZBfEpuZec5JSG7AqSX54OecisPy/PzJB2/+qKmzN5dOPszMU2bDj8sWqEYUHjimcEbLKBgFo2AUjAIiAABbZlWptv4jGQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-1647-5495","institution":"Universite de Monastir Faculte de Medecine de Monastir","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"ahlem","middleName":"","lastName":"helaoui","suffix":""},{"id":98373042,"identity":"736822e5-d522-441e-8c3a-bb4c0f30a54b","order_by":1,"name":"Sana Sfar","email":"","orcid":"","institution":"Universite de Monastir Faculte de Medecine de Monastir","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sana","middleName":"","lastName":"Sfar","suffix":""},{"id":98373043,"identity":"6085f932-12a0-48ce-aba4-9925616782a7","order_by":2,"name":"Najet Boudhiba","email":"","orcid":"","institution":"Universite de Monastir Faculte de Medecine de Monastir","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Najet","middleName":"","lastName":"Boudhiba","suffix":""},{"id":98373044,"identity":"f5152da9-faf8-46c4-9486-a6727ababc36","order_by":3,"name":"Fariba Dehghanian","email":"","orcid":"","institution":"University of Isfahan Faculty of Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fariba","middleName":"","lastName":"Dehghanian","suffix":""},{"id":98373045,"identity":"278c104e-251d-478e-817e-bc6e16cfcc54","order_by":4,"name":"Moein Dehbashi","email":"","orcid":"","institution":"University of Isfahan Faculty of 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Monastir","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Abderraouf","middleName":"","lastName":"KENANI","suffix":""}],"badges":[],"createdAt":"2022-04-09 13:04:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1540515/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1540515/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20356777,"identity":"af92221f-4f87-42d1-957b-f2e120766bbf","added_by":"auto","created_at":"2022-04-14 17:06:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":363522,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptAhlemHELAOUI.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1540515/v1_covered.pdf"},{"id":20356776,"identity":"ae4fa579-a25b-444c-80ce-c2e83d72855d","added_by":"auto","created_at":"2022-04-14 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section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"molecular-biology-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mole","sideBox":"Learn more about [Molecular Biology Reports](https://www.springer.com/journal/11033)","snPcode":"11033","submissionUrl":"https://submission.nature.com/new-submission/11033/3","title":"Molecular Biology Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cervical cancer, Xenobiotic-metabolizing genes, AhR, CYP1A1, GSTM1, and GSTT1.","lastPublishedDoi":"10.21203/rs.3.rs-1540515/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1540515/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Host genetic characteristics and environmental factors interactions may play a crucial role in cervical carcinogenesis. We investigated the impact of functional genetic variants of four xenobiotic-metabolizing genes (AhR, CYP1A1, GSTM1, and GSTT1) on cervical cancer development in Tunisian women. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The AhR gene polymorphism was analyzed using the tetra-primer ARMS-PCR, whereas the CYP1A1 polymorphism genotypes were identified by PCR-RFLP. A multiplex ligation-dependent polymerase chain reaction approach was applied for the analysis of GSTM1 and GSTT1 polymorphisms. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The homozygous A/A genotype of the AhR gene (rs2066853) and the heterozygous T/C genotype of the CYP1A1 SNP (CYP1A1-MspI) appeared to be associated with an increased risk of cervical tumorigenesis (ORa = 2.81; ORa = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (ORa = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (ORa = 1.18; p = 0.784). Considering the combined effect, we noted a significantly higher association with cancer risk for individuals with at least two high-risk genotypes of CYP1A1/GSTT1 (ORa = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (ORa = 11.3) and individuals with at least two high-risk genotypes of CYP1A1/GSTM1/GSTT1/AhR exploitation low-risk genotype as a reference. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This study indicated that the single-gene contribution and the combined effect of xenobioticmetabolizing gene polymorphisms (AhR, CYP1A1-MspI, GSTM1, and GSTT1) may have a considerable association with increased cervical cancer risk.\u003c/p\u003e","manuscriptTitle":"Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-14 17:06:01","doi":"10.21203/rs.3.rs-1540515/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2022-06-08T13:31:05+00:00","index":0,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-04-27T22:15:52+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-04-13T10:47:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-04-12T06:43:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Molecular Biology Reports","date":"2022-04-09T09:04:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"molecular-biology-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mole","sideBox":"Learn more about [Molecular Biology Reports](https://www.springer.com/journal/11033)","snPcode":"11033","submissionUrl":"https://submission.nature.com/new-submission/11033/3","title":"Molecular Biology Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1201e535-ce98-4a47-a903-29f191cb3efa","owner":[],"postedDate":"April 14th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-09-12T16:08:42+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-14 17:06:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1540515","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1540515","identity":"rs-1540515","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}