Näytä suppeat kuvailutiedot

dc.contributor.authorSievänen, Tero
dc.contributor.authorJokela, Tiina
dc.contributor.authorHyvärinen, Matti
dc.contributor.authorKorhonen, Tia-Marje
dc.contributor.authorPylvänäinen, Kirsi
dc.contributor.authorMecklin, Jukka-Pekka
dc.contributor.authorKarvanen, Juha
dc.contributor.authorSillanpää, Elina
dc.contributor.authorSeppälä, Toni T.
dc.contributor.authorLaakkonen, Eija K.
dc.date.accessioned2024-10-24T04:53:14Z
dc.date.available2024-10-24T04:53:14Z
dc.date.issued2024
dc.identifier.citationSievänen, T., Jokela, T., Hyvärinen, M., Korhonen, T.-M., Pylvänäinen, K., Mecklin, J.-P., Karvanen, J., Sillanpää, E., Seppälä, T. T., & Laakkonen, E. K. (2024). Circulating microRNA signature predicts cancer incidence in Lynch syndrome : a pilot study. <i>Cancer Prevention Research</i>, <i>17</i>(6), 243-254. <a href="https://doi.org/10.1158/1940-6207.capr-23-0368" target="_blank">https://doi.org/10.1158/1940-6207.capr-23-0368</a>
dc.identifier.otherCONVID_207833194
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/97653
dc.description.abstractLynch syndrome (LS) is the most common autosomal dominant cancer syndrome and is characterized by high genetic cancer risk modified by lifestyle factors. This study explored whether a circulating microRNA (c-miR) signature predicts LS cancer incidence within a 4-year prospective surveillance period. To gain insight how lifestyle behavior could affect LS cancer risk, we investigated whether the cancer-predicting c-miR signature correlates with known risk-reducing factors such as physical activity, body mass index (BMI), dietary fiber or non-steroidal anti-inflammatory drug usage. The study included 110 c-miR samples from LS carriers, 18 of whom were diagnosed with cancer during a 4-year prospective surveillance period. Lasso regression was utilized to find c-miRs associated with cancer risk. Individual risk sum derived from the chosen c-miRs was used to develop a model to predict LS cancer incidence. This model was validated using 5-fold cross-validation. Correlation and pathway analyses were applied to inspect biological functions of c-miRs. Pearson correlation was used to examine the associations of c-miR risk sum and lifestyle factors. Hsa-miR-10b-5p, hsa-miR-125b-5p, hsa-miR-200a-3p, hsa-miR-3613-5p and hsa-miR-3615 were identified as cancer predictors by Lasso, and their risk sum score associated with higher likelihood of cancer incidence (HR 2.72, 95% CI 1.64-4.52, C-index=0.72). In cross-validation, the model indicated good concordance with the average C-index of 0.75 (0.6-1.0). Co-regulated hsa-miR-10b-5p, hsa-miR-125b-5p and hsa-miR-200a-3p targeted genes involved in cancer-associated biological pathways. The c-miR risk sum score correlated with BMI (r=0.23, p<0.01). In summary, BMI-associated c-miRs predict LS cancer incidence within four years, although further validation is required.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.relation.ispartofseriesCancer Prevention Research
dc.rightsCC BY-NC-ND 4.0
dc.titleCirculating microRNA signature predicts cancer incidence in Lynch syndrome : a pilot study
dc.typeresearch article
dc.identifier.urnURN:NBN:fi:jyu-202410246510
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosMatematiikan ja tilastotieteen laitosfi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.contributor.laitosDepartment of Mathematics and Statisticsen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.format.pagerange243-254
dc.relation.issn1940-6207
dc.relation.numberinseries6
dc.relation.volume17
dc.type.versionpublishedVersion
dc.rights.copyright© 2024 The Authors; Published by the American Association for Cancer Research
dc.rights.accesslevelopenAccessfi
dc.type.publicationarticle
dc.relation.grantnumber101026706
dc.relation.grantnumber101026706
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/H2020/101026706/EU//cmiRCan
dc.subject.ysoriskitekijät
dc.subject.ysosairastavuus
dc.subject.ysofyysinen aktiivisuus
dc.subject.ysoLynchin oireyhtymä
dc.subject.ysosyöpätaudit
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p13277
jyx.subject.urihttp://www.yso.fi/onto/yso/p3556
jyx.subject.urihttp://www.yso.fi/onto/yso/p23102
jyx.subject.urihttp://www.yso.fi/onto/yso/p23697
jyx.subject.urihttp://www.yso.fi/onto/yso/p678
dc.rights.urlhttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.relation.doi10.1158/1940-6207.capr-23-0368
dc.relation.funderEuropean Commissionen
dc.relation.funderEuroopan komissiofi
jyx.fundingprogramMSCA Individual Fellowship (IF)en
jyx.fundingprogramMSCA Individual Fellowship (IF)fi
jyx.fundinginformationWe would like to extend our gratitude to prof. Sarianna Sipilä (Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Finland) for the lifestyle data acquisition. E.K. Laakkonen was supported by grants from Päivikki and Sakari Sohlberg Foundation. T. Jokela was supported by European Commission Union Marie Skłodowska-Curie Individual Fellowships (Grant number: H2020- 447 MSCA-IF-2020 #101026706) T.T. Seppälä was supported by funding from the Academy of Finland and iCAN Precision Medicine Flagship of Academy of Finland, and research grants by Jane and Aatos Erkko Foundation, Finnish Medical Foundation, Sigrid Juselius Foundation, Emil Aaltonen Foundation, Cancer Foundation Finland, Relander Foundation, and state research funding from the Finnish Goverment, which is allocated as competed grants through employing institutions to researchers within their university hospital co-operation area (Tampere University Hospital / Helsinki University Hospital).
dc.type.okmA1


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