Breast cancer risk and polymorphisms in genes involved in metabolism of estrogens (CYP17, HSD17β1, COMT and MnSOD): Possible protective role of MnSOD gene polymorphism Val/Ala and Ala/Ala in women that never breast fed

Silva, Susana N.; Cabral, Marisa N; Castro, Guilherme Bezerra de; Pires, M. Rebordão; Azevedo, Ana Paula; Manita, Isabel; Pina, João Murta; Rueff, José; Gaspar, Jorge

doi:10.3892/or.16.4.781

Cited by 23 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, we validated this methodology towards its application for identification of genetic polymorphisms potentially associated with individual cancer risk. We generated seven different DNA pools with 50 DNA samples from a population previously genotyped for the MTHFR (C677T) polymorphism creating different amounts of each allele (10,20,40, 50, 60, 80, 90% for common allele). The results obtained (data not shown) demonstrated the reproducibility of this methodology when the allelic frequencies between individual and pooled genotyping were compared.…”

Section: Resultsmentioning

confidence: 99%

“…The studied DNA samples are routinely used in our laboratory for breast cancer association studies, including DNA samples from the Xavante Indian population which is characterized by an absolute absence of breast cancer (20). All DNA samples were extracted from 250 µl of whole blood using a commercially available kit according to the manufacturer's instructions (QIAamp DNA extraction kit; Qiagen, Hilden, Germany).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

SNPs/Pools: A methodology for the identification of relevant SNPs in breast cancer epidemiology

Silva

Guerreiro²,

Gomes³

et al. 2011

Oncol Rep

Self Cite

View full text Add to dashboard Cite

Abstract. The identification of allelic variants of human genes is of great importance when assessing genetic susceptibility. The emerging role of genetic polymorphisms in association studies has created the need for high throughput genotyping methodologies that allow a more rapid identification of relevant polymorphisms related to individual cancer risk enabling the extension to large-scale association studies. DNA pooling methodology may be of great importance considering the cost, time and labor that are involved in large-scale genotyping analysis carried out on individual samples. Alternatively, when using pooled samples which are made up of DNA from many individuals treated as a single sample, these factors are decrease drastically. In this way, the use of DNA pooling methodology, as a pre-selection tool, allows the identification of the most relevant polymorphisms to be studied, facilitating the estimation of the allelic frequency of each SNP in different populations. The present study initially aimed to validate the DNA pooling approach for the identification of genetic polymorphisms potentially associated with individual cancer risk generating pools with known allelic frequencies and using studies ongoing in the laboratory. Finally, our main aim was to test the accuracy of the pooled DNA analysis comparing the results of the allelic frequencies determined using pooled samples with the allelic frequency previously estimated by individual genotyping and previously published. In order to analyze the possibility of establishing differences between populations, we created DNA pools using a Portuguese control population, a breast cancer population and a Xavante Indian population characterized by a total absence of breast cancer cases. The pools were firstly created with known allelic frequencies, previously determined by individual genotyping, and, latter, randomly incremented in sample size to 200 patients and controls. Our results showed that the DNA pooling approach was a useful tool for the analysis of allelic distribution in the different populations studied. Ιn conclusion, our results showed that this methodology can be applied as an effective approach to identify SNPs of importance in genetic susceptibility to disease which may be used in association studies conducted subsequently by individual genotyping. IntroductionSingle nucleotide polymorphisms (SNPs) occur frequently throughout the human genome and are the most common type of markers used in genetic analysis (1,2). They are useful for epidemiologic studies to evaluate the role of genetic variants in the aetiology of human disease (3). The identification of allelic variants of human genes is thus fundamental to the assessment of genetic susceptibility in an individual genetic analysis. Consequently, more association studies are necessary to identify, in candidate genes, alleles that may confer small increments in individual susceptibility to disease (4).The case control studies carried out to date have shown that SNPs increase the disease risk by a...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

SNPs/Pools: A methodology for the identification of relevant SNPs in breast cancer epidemiology

Silva

Guerreiro²,

Gomes³

et al. 2011

Oncol Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several studies have postulated that Ala-9Val MnSOD polymorphism and cancer association are influenced by variables, such as food (vegetables and meat), high alcohol consumption, smoking habit, pesticide exposition (1,8,26,27) . Some studies reported possible gene-gene association, such as performed by Cox et al (5) , that described interaction MnSOD and glutathione peroxidase (GPX-1) gene polymorphisms associated with increased risk of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Association of manganese superoxide dismutase gene polymorphism (Ala-9Val) and breast cancer in males and females

Bica

Cruz²,

Silva³

et al. 2007

J. Bras. Patol. Med. Lab.

View full text Add to dashboard Cite

Introduction: One of the several metabolic pathways involved in breast carcinogenesis is the human polymorphism in the mitochondrial targeting sequence Ala-9Val of the manganese superoxide dismutase (MnSOD) gene, which has been previously associated with increased risk of breast cancer in females. Since there is no previous report on this polymorphism in male breast cancer, the objective of this study is to analyze MnSOD polymorphism in a population of males and females with breast cancer from the southernmost state of Brazil, compared to healthy controls. Methods: A case-control study of one hundred patients affected by breast cancer (11 men and 89 women) and 370 healthy age-adjusted database controls was performed. DNA was extracted from paraffin-embedded tumoral tissue. MnSOD polymorphism was determined by PCR-RFLP techniques using restriction enzyme Hae III. Chi-square test was used to compare MnSOD frequency distribution. Results: MnSOD genotypic frequencies in all patients with breast cancer were AA = 15%; AV = 56%; VV = 29% and controls AA = 6.5%; AV = 68.1% and VV = 25.4%. Both male and female patients with breast cancer presented significantly higher AA frequencies compared to controls (p = 0.035), suggesting strong association of this genotype with breast cancer. A 2.15-fold (95% confidence interval [CI] 1.393-4.541) risk of breast cancer was found among individuals carrying the MnSOD AA allele-containing genotypes compared with the MnSOD VV and AV genotypes. Discussion: These results confirm the already established association of MnSOD AA genotype with female breast cancer and further indicate a similar frequency distribution and increased risk in the male population.

show abstract

“…These genes are usually involved in the metabolism of environmental carcinogens, in the repair of DNA lesions induced by exogenous and endogenous carcinogens, and in the control of the cell cycle. Individual polymorphic forms in those genes have been associated with individual susceptibility to different types of cancer namely in breast and thyroid cancer (Conde et al, 2009;Gaspar et al, 2004;Pabalan et al, 2010;Peng et al, 2011;Silva et al, 2005;Silva et al, 2006b;Silva et al, 2006a;Silva et al, 2009;Silva et al, 2010;Silva et al, 2007). Several enzymes have evolved for the detoxification of xenobiotic compounds, and their gene expression is induced in response to the presence of numerous compounds (e.g., polycyclic aromatic hydrocarbons found in tobacco smoke).…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Perspectives in Thyroid and Breast Cancer: The Role of DNA Repair Polymorphisms

Silva

Gomes

Rueff

et al. 2011

DNA Repair and Human Health

View full text Add to dashboard Cite

Breast cancer risk and polymorphisms in genes involved in metabolism of estrogens (CYP17, HSD17β1, COMT and MnSOD): Possible protective role of MnSOD gene polymorphism Val/Ala and Ala/Ala in women that never breast fed

Cited by 23 publications

References 24 publications

SNPs/Pools: A methodology for the identification of relevant SNPs in breast cancer epidemiology

SNPs/Pools: A methodology for the identification of relevant SNPs in breast cancer epidemiology

Association of manganese superoxide dismutase gene polymorphism (Ala-9Val) and breast cancer in males and females

DNA Repair Perspectives in Thyroid and Breast Cancer: The Role of DNA Repair Polymorphisms

Contact Info

Product

Resources

About