{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T22:14:28Z","timestamp":1774908868459,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cValidation of risk assessment model for breast cancer based on genetic polymorphisms of low penetrance to assess breast cancer risk\u201d","award":["PTDC\/DTPPIC\/4743\/2014"],"award-info":[{"award-number":["PTDC\/DTPPIC\/4743\/2014"]}]},{"name":"\u201cValidation of risk assessment model for breast cancer based on genetic polymorphisms of low penetrance to assess breast cancer risk\u201d","award":["POCI-01-0145-FEDER-16620"],"award-info":[{"award-number":["POCI-01-0145-FEDER-16620"]}]},{"name":"\u201cValidation of risk assessment model for breast cancer based on genetic polymorphisms of low penetrance to assess breast cancer risk\u201d","award":["SFRH\/BD146395\/2019"],"award-info":[{"award-number":["SFRH\/BD146395\/2019"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["PTDC\/DTPPIC\/4743\/2014"],"award-info":[{"award-number":["PTDC\/DTPPIC\/4743\/2014"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["POCI-01-0145-FEDER-16620"],"award-info":[{"award-number":["POCI-01-0145-FEDER-16620"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["SFRH\/BD146395\/2019"],"award-info":[{"award-number":["SFRH\/BD146395\/2019"]}]},{"name":"CICS-UBI\u2019s core funding DOI: 10.54499\/UIDB\/00709\/2020","award":["PTDC\/DTPPIC\/4743\/2014"],"award-info":[{"award-number":["PTDC\/DTPPIC\/4743\/2014"]}]},{"name":"CICS-UBI\u2019s core funding DOI: 10.54499\/UIDB\/00709\/2020","award":["POCI-01-0145-FEDER-16620"],"award-info":[{"award-number":["POCI-01-0145-FEDER-16620"]}]},{"name":"CICS-UBI\u2019s core funding DOI: 10.54499\/UIDB\/00709\/2020","award":["SFRH\/BD146395\/2019"],"award-info":[{"award-number":["SFRH\/BD146395\/2019"]}]},{"DOI":"10.13039\/501100001871","name":"FCT PhD fellowship","doi-asserted-by":"publisher","award":["PTDC\/DTPPIC\/4743\/2014"],"award-info":[{"award-number":["PTDC\/DTPPIC\/4743\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT PhD fellowship","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-16620"],"award-info":[{"award-number":["POCI-01-0145-FEDER-16620"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"FCT PhD fellowship","doi-asserted-by":"publisher","award":["SFRH\/BD146395\/2019"],"award-info":[{"award-number":["SFRH\/BD146395\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood\/surrounding\/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood\/surrounding tissue (p-value = 0.023) and tumour\/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.<\/jats:p>","DOI":"10.3390\/cancers16132411","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:17:29Z","timestamp":1719821849000},"page":"2411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Micaela","family":"Almeida","sequence":"first","affiliation":[{"name":"Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Clinical Academic Centre of Beiras (CACB), Edif\u00edcio UBImedical, Estrada Municipal 506, 6200 Covilh\u00e3, Portugal"},{"name":"Department of Pathology, Ipatimup Diagnostics, Rua J\u00falio Amaral de Carvalho, 45, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-2604","authenticated-orcid":false,"given":"Catarina L.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Clinical Academic Centre of Beiras (CACB), Edif\u00edcio UBImedical, Estrada Municipal 506, 6200 Covilh\u00e3, Portugal"}]},{"given":"Rosa Maria","family":"Tom\u00e9","sequence":"additional","affiliation":[{"name":"Clinical Academic Centre of Beiras (CACB), Edif\u00edcio UBImedical, Estrada Municipal 506, 6200 Covilh\u00e3, Portugal"},{"name":"Cova da Beira Local Health Unit, Alameda P\u00earo da Covilh\u00e3, 6200-251 Covilh\u00e3, Portugal"}]},{"given":"Jos\u00e9","family":"Fonseca-Moutinho","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Clinical Academic Centre of Beiras (CACB), Edif\u00edcio UBImedical, Estrada Municipal 506, 6200 Covilh\u00e3, Portugal"},{"name":"Cova da Beira Local Health Unit, Alameda P\u00earo da Covilh\u00e3, 6200-251 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8312-1681","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Pol\u00f3nia","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ipatimup Diagnostics, Rua J\u00falio Amaral de Carvalho, 45, 4200-135 Porto, Portugal"},{"name":"Escola de Medicina e Ci\u00eancias Biom\u00e9dicas, Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, Funda\u00e7\u00e3o Fernando Pessoa (FP-I3ID), Avenida Fernando Pessoa, 150, 4420-096 Gondomar, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4783-665X","authenticated-orcid":false,"given":"Ana Cristina","family":"Ramalhinho","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Clinical Academic Centre of Beiras (CACB), Edif\u00edcio UBImedical, Estrada Municipal 506, 6200 Covilh\u00e3, Portugal"},{"name":"Cova da Beira Local Health Unit, Alameda P\u00earo da Covilh\u00e3, 6200-251 Covilh\u00e3, Portugal"}]},{"given":"Luiza","family":"Breitenfeld","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"Clinical Academic Centre of Beiras (CACB), Edif\u00edcio UBImedical, Estrada Municipal 506, 6200 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,29]]},"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 A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.tcb.2012.08.001","article-title":"The nuclear factor kappa B signaling pathway: Integrating metabolism with inflammation","volume":"22","author":"Tornatore","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Smolarz, B., Nowak, A.Z., and Romanowicz, H. (2022). 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