Erika Korobeinikova, Rasa Ugenskiene, Ruta Insodaite, Viktoras Rudzianskas, Jurgita Gudaitiene, Elona Juozaityte
{"title":"氧化应激相关基因功能多态性在早期乳腺癌存活中的作用","authors":"Erika Korobeinikova, Rasa Ugenskiene, Ruta Insodaite, Viktoras Rudzianskas, Jurgita Gudaitiene, Elona Juozaityte","doi":"10.1177/17246008211011177","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer.</p><p><strong>Methods: </strong>The current study investigated the associations of functional single nucleotide polymorphisms in the <i>NFE2L2</i>, <i>HMOX1, P21</i>, <i>TXNRD2</i>, and <i>ATF3</i> genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I-II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays.</p><p><strong>Results: </strong>The CA+AA genotypes of <i>P21</i> rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (<i>P</i>=0.041 and <i>P</i>=0.022, respectively). The TT genotype in <i>ATF3</i> rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (<i>P</i>=0.023, <i>P</i>=0.046, and <i>P</i>=0.040, respectively). In both, univariate and multivariate Cox analysis, <i>TXNRD2</i> rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; <i>P</i>=0.025) and overall survival (multivariate HR 2.248; <i>P</i>=0.029). The <i>ATF3</i> rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; <i>P</i>=0.006), metastasis-free survival (multivariate HR 4.759; <i>P</i>=0.018), and overall survival (multivariate HR 3.280; <i>P</i>=0.048).</p><p><strong>Conclusion: </strong>Our findings suggest that <i>P21</i> rs1801270 is associated with lymph node metastasis and larger tumor size, and <i>ATF3</i> rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, <i>TXNRD2</i> rs1139793 and <i>ATF3</i> rs11119982, were detected. Further investigations are needed to confirm the results of the current study.</p>","PeriodicalId":50334,"journal":{"name":"International Journal of Biological Markers","volume":"36 2","pages":"14-21"},"PeriodicalIF":2.3000,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17246008211011177","citationCount":"4","resultStr":"{\"title\":\"The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival.\",\"authors\":\"Erika Korobeinikova, Rasa Ugenskiene, Ruta Insodaite, Viktoras Rudzianskas, Jurgita Gudaitiene, Elona Juozaityte\",\"doi\":\"10.1177/17246008211011177\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer.</p><p><strong>Methods: </strong>The current study investigated the associations of functional single nucleotide polymorphisms in the <i>NFE2L2</i>, <i>HMOX1, P21</i>, <i>TXNRD2</i>, and <i>ATF3</i> genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I-II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays.</p><p><strong>Results: </strong>The CA+AA genotypes of <i>P21</i> rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (<i>P</i>=0.041 and <i>P</i>=0.022, respectively). The TT genotype in <i>ATF3</i> rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (<i>P</i>=0.023, <i>P</i>=0.046, and <i>P</i>=0.040, respectively). In both, univariate and multivariate Cox analysis, <i>TXNRD2</i> rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; <i>P</i>=0.025) and overall survival (multivariate HR 2.248; <i>P</i>=0.029). The <i>ATF3</i> rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; <i>P</i>=0.006), metastasis-free survival (multivariate HR 4.759; <i>P</i>=0.018), and overall survival (multivariate HR 3.280; <i>P</i>=0.048).</p><p><strong>Conclusion: </strong>Our findings suggest that <i>P21</i> rs1801270 is associated with lymph node metastasis and larger tumor size, and <i>ATF3</i> rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, <i>TXNRD2</i> rs1139793 and <i>ATF3</i> rs11119982, were detected. Further investigations are needed to confirm the results of the current study.</p>\",\"PeriodicalId\":50334,\"journal\":{\"name\":\"International Journal of Biological Markers\",\"volume\":\"36 2\",\"pages\":\"14-21\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2021-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1177/17246008211011177\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Biological Markers\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17246008211011177\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/4/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Markers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17246008211011177","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/4/22 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival.
Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer.
Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I-II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays.
Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048).
Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.
期刊介绍：
IJBM is an international, online only, peer-reviewed Journal, which publishes original research and critical reviews primarily focused on cancer biomarkers. IJBM targets advanced topics regarding the application of biomarkers in oncology and is dedicated to solid tumors in adult subjects. The clinical scenarios of interests are screening and early diagnosis of cancer, prognostic assessment, prediction of the response to and monitoring of treatment.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
