{"title":"Association of <i>RAD51</i>, <i>XRCC1</i>, <i>XRCC2</i>, and <i>XRCC3</i> Polymorphisms with Risk of Breast Cancer.","authors":"Priyanka Gupta, Vasudha Sambyal, Kamlesh Guleria, Manjit Singh Uppal, Meena Sudan","doi":"10.1089/gtmb.2023.0012","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, <i>RAD51</i> rs1801320, <i>XRCC1</i> rs25487, <i>XRCC2</i> rs3218536, and <i>XRCC3</i> rs861539 with the risk of breast cancer. <b><i>Materials and Methods:</i></b> In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. <b><i>Results:</i></b> The GC genotype (<i>p</i> = 0.018) and the combined GC+CC (<i>p</i> = 0.03) genotypes of <i>RAD51</i> rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype (<i>p</i> = 0.0001), the combined CT+TT genotypes (<i>p</i> = 0.0002), and the T allele (<i>p</i> = 0.0019) of <i>XRCC3</i> rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of <i>XRCC1</i> rs25487 and <i>XRCC2</i> rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between <i>XRCC3</i> and <i>XRCC2</i>. String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. <b><i>Conclusion:</i></b> <i>RAD51</i> rs1801320 and <i>XRCC3</i> rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among <i>XRCC1</i>, <i>XRCC2</i>, <i>XRCC3</i>, and <i>RAD51</i>.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2023.0012","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, RAD51 rs1801320, XRCC1 rs25487, XRCC2 rs3218536, and XRCC3 rs861539 with the risk of breast cancer. Materials and Methods: In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. Results: The GC genotype (p = 0.018) and the combined GC+CC (p = 0.03) genotypes of RAD51 rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype (p = 0.0001), the combined CT+TT genotypes (p = 0.0002), and the T allele (p = 0.0019) of XRCC3 rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of XRCC1 rs25487 and XRCC2 rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between XRCC3 and XRCC2. String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. Conclusion:RAD51 rs1801320 and XRCC3 rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among XRCC1, XRCC2, XRCC3, and RAD51.
期刊介绍:
Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results.
Genetic Testing and Molecular Biomarkers coverage includes:
-Diagnosis across the life span-
Risk assessment-
Carrier detection in individuals, couples, and populations-
Novel methods and new instrumentation for genetic testing-
Results of molecular, biochemical, and cytogenetic testing-
Genetic counseling