Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer

Bica, Cláudia Giuliano; Silva, Leonardo Leiria de Moura da; Toscani, Nadima Vieira; Zettler, Cláudio Galleano; Gottlieb, Maria Gabriela Valle; Alexandre, Cláudio Osmar Pereira; Graudenz, Márcia Silveira; Cruz, Ivana Beatrice Mânica da

doi:10.1016/j.cancergencyto.2009.09.011

Cited by 20 publications

(10 citation statements)

References 27 publications

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“…Therefore, we postulated that an MnSOD gene presents a dual protective characteristic dependent on toxic agents (Figure 3). This dual characteristic is similar to that observed in the association between the Ala16Val MnSOD gene polymorphism and susceptibility to non-transmissible diseases (Bica et al, 2010).…”

Section: Discussionsupporting

confidence: 65%

“…Interestingly, in some cases, the disease risk is associated with the A allele or AA genotype -for example, in prostate cancer (Taufer et al, 2005), breast cancer (Bica et al, 2009), and other cancers. Disease risk is linked to the V allele or VV genotype in diabetes microvascular complications (Tian et al, 2011), obesity (Montano et al, 2009), hypercholesterolemia (Duarte et al, 2010), and metastatic potential of breast cancer (Bica et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury

Algarve¹,

Barbisan²,

Ribeiro³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Environmental contamination by methylmercury (MeHg)is an enormous public health problem in world regions such as Amazonia. MeHg toxic effects seem to be influenced by environmental and genetic factors. However, few studies have evaluated the genetic influences of MeHg toxicity in humans. Therefore, the aim of this study was to evaluate the genetic influence of Ala16Val manganese superoxide dismutase gene polymorphism (Ala16Val-MnSOD) on the cytotoxic effects of in vitro human leukocytes exposed to MeHg. Subjects were selected from 100 individuals aged 26.4 ± 7.3 years genotyped to Ala16Val-MnSOD Effects of Ala16Val MnSOD polymorphism on MeHg-exposed WBCs polymorphism (AA = 6, VV = 6, and AV = 12) to perform in vitro testing using white blood cells (WBCs). Reactive oxygen species production was measured using 2',7'-dichlorofluorescein diacetate fluorimetric assay, and cell viability was measured using MTT assay on WBC samples from the same subjects that were both exposed and not exposed to MeHg (2.5 µM for 6 h). The results showed that AA-and VV-WBCs exposed to MeHg did not display increased reactive oxygen species levels compared to those in cells that were not exposed. However, AVleukocytes exposed to MeHg displayed increased ROS levels. Cellular viability comparison among genotypes exposed to MeHg showed that the viability of AA-WBCs was lower than that of VV-WBC, with mean values of 3.46 ± 0.13 and 3.08 ± 0.77 (standard error), respectively (P = 0.033), whereas heterozygous cells (AV) displayed intermediate values.This difference was likely due to the higher basal H 2 O 2 production of AA-WBCs compared to that of other genotypes. These results suggest that the Ala16Val-MnSOD polymorphism has toxicogenetic effects in human cells exposed to MeHg.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury

Algarve¹,

Barbisan²,

Ribeiro³

et al. 2013

Genet. Mol. Res.

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“…Some studies suggest that the SOD2 polymorphism acts as a predictor of response to chemotherapy in cancer patients [2]–[5]. Research has also suggested that the Ala/Ala genotype may be associated with an approximately two-fold increase in risk of breast cancer [6]–[8], but that the Val/Val genotype may correlate with tumors with higher metastatic potential (lymph node positive disease) [9]. Its association with breast cancer recurrence is not clear because of conflicting findings from the seven former studies [10]–[15].…”

Section: Introductionmentioning

confidence: 99%

Manganese Superoxide Dismutase and Breast Cancer Recurrence: A Danish Clinical Registry-Based Case-Control Study, and a Meta-Analysis

et al. 2014

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BackgroundManganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses.MethodsWe conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non-metastatic breast cancer from 1990–2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95% confidence intervals (95% CI) of BCR. We used random-effects meta-analytic models to evaluate the association of SOD2 polymorphisms and BCR.ResultsThe frequency of the SOD2-Ala allele was 70% in cases versus 71% in controls; 40% versus 44% were heterozygotes, and 30% versus 25% were homozygotes, respectively. Heterozygote and homozygote carriers of the Ala allele had no increased rate of BCR (OR = 1.1, 95%CI = 0.65, 2.0, and OR = 0.87, 95%CI = 0.47, 1.6, respectively). Five studies informed the meta-analytic models; summary estimates associating BCR for homozygote, or any inheritance of the variant Ala allele were 1.18 (95%CI = 0.74, 1.88), and 1.18, (95%CI = 0.91, 1.54), respectively.ConclusionOur findings do not suggest that MnSOD enzymatic activity, as measured by SOD2 genotype, affects rates of BCR among patients treated with Cyclo.

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“…TIMP-1 overproduction slowed chemical carcinogenesis in skin and liver carcinogenesis in transgenic mice (Martin et al, 1996;Buck et al, 1999;Bica et al, 2010). TIMPs, aside from inhibition MMP (Valente et al, 1998), also could suppress receptor tyrosine kinase signaling independent of metalloproteinase inhibition (Stetler-Stevenson, 2008).…”

Section: Discussionmentioning

confidence: 99%

Curcumin Effect on MMPs and TIMPs Genes in a Breast Cancer Cell Line

Hassan¹,

Daghestani²

2012

Asian Pacific Journal of Cancer Prevention

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Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer

Cited by 20 publications

References 27 publications

In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury

In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury

Manganese Superoxide Dismutase and Breast Cancer Recurrence: A Danish Clinical Registry-Based Case-Control Study, and a Meta-Analysis

Curcumin Effect on MMPs and TIMPs Genes in a Breast Cancer Cell Line

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