Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer

Bielińska, Beata; Gaj, Paweł; Kluska, Anna; Nowakowska, Dorota; Bałabas, Aneta; Dąbrowska, Michalina; Niwińska, Anna; Gruchota, Jakub; Zub, Renata; Skasko, E.; Steffen, Jan; Ostrowski, Jerzy; Siedlecki, Janusz A.

doi:10.1007/s10689-013-9647-6

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Of notice, these findings parallel the recent findings by Hitchins and colleagues described above [38] with respect to MLH1 methylation in a colorectal cancer family. Notably, while BRCA1 promoter variants influencing breast and ovarian cancer risk have been reported earlier [141, 142], the finding by Evans et al is the first to link such variants to BRCA1 methylation status.…”

Section: Normal Tissue Brca1/2 Methylation and Risk Of Breast And Ovamentioning

confidence: 95%

Constitutional Mosaic Epimutations – a hidden cause of cancer?

Lønning¹,

Eikesdal²,

Løes³

et al. 2019

CST

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Silencing of tumor suppressor genes by promoter hypermethylation is a key mechanism to facilitate cancer progression in many malignancies. While promoter hypermethylation can occur at later stages of the carcinogenesis process, constitutional methylation of key tumor suppressors may be an initiating event whereby cancer is started. Constitutional BRCA1 methylation due to cis -acting germline genetic variants is associated with a high risk of breast and ovarian cancer. However, this seems to be a rare event, restricted to a very limited number of families. In contrast, mosaic constitutional BRCA1 methylation is detected in 4-7% of newborn females without germline BRCA1 mutations. While the cause of such methylation is poorly understood, mosaic normal tissue BRCA1 methylation is associated with a 2-3 fold increased risk of high-grade serous ovarian cancer (HGSOC). As such, BRCA1 methylation may be the cause of a significant number of ovarian cancers. Given the molecular similarities between HGSOC and basal-like breast cancer, the findings with respect to HGSOC suggest that constitutional BRCA1 methylation could be a risk factor for basal-like breast cancer as well. Similar to BRCA1 , some specific germline variants in MLH1 and MSH2 are associated with promoter methylation and a high risk of colorectal cancers in rare hereditary cases of the disease. However, as many as 15% of all colorectal cancers are of the microsatellite instability (MSI) “high” subtype, in which commonly the tumors harbor MLH1 hypermethylation. Constitutional mosaic methylation of MLH1 in normal tissues has been detected but not formally evaluated as a potential risk factor for incidental colorectal cancers. However, the findings with respect to BRCA1 in breast and ovarian cancer raises the question whether mosaic MLH1 methylation is a risk factor for MSI positive colorectal cancer as well. As for MGMT , a promoter variant is associated with elevated methylation across a panel of solid cancers, and MGMT promoter methylation may contribute to an elevated cancer risk in several of these malignancies. We hypothesize that constitutional mosaic promoter methylation of crucial tumor suppressors may trigger certain types of cancer, similar to germline mutations inactivating the same particular genes. Such constitutional methylation events may be a spark to ignite cancer development, and if associated with a significant cancer risk, screening for such epigenetic alterations could be part of cancer prevention programs to reduce cancer mortality in the future.

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Section: Normal Tissue Brca1/2 Methylation and Risk Of Breast And Ovamentioning

confidence: 95%

Constitutional Mosaic Epimutations – a hidden cause of cancer?

Lønning¹,

Eikesdal²,

Løes³

et al. 2019

CST

View full text Add to dashboard Cite

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“…Several recent studies suggested the possible of gene polymorphism (Bielinska et al, 2013;Liu et al, 2013;Ramalhinho et al, 2013) or JAK2/STAT3 pathway alteration (Teng et al, 2013) as the risk of breast cancer in population. In addition to genetic factors, there are a number of distinctive environmental that may contribute to the variable rates of incidence in this population.…”

Section: 3815 Age Distribution Of Breast Cancer From a Thailand Popumentioning

confidence: 99%

Age Distribution of Breast Cancer from a Thailand Population-Based Cancer Registry

Kotepui¹,

Chupeerach²

2013

Asian Pacific Journal of Cancer Prevention

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“…Our study did not exclude the possible contribution of other SNPs within this gene in BC nor substantial contribution These studies had NOS scores of 6 to 9 and assessed rs11655505 [9, [13][14][15][16], rs1799966 [4,8,17], rs3737559 [10,18], rs1799950 [8,10,17,19,20], rs799917 [4,17,[21][22][23] or rs16941 [17,24]. Assessment of genotype distribution in control groups of all included researches showed their compliance with HWE.…”

Section: Resultsmentioning

confidence: 99%

Meta-Analysis of BRCA1 Polymorphisms and Breast Cancer Susceptibility

Ghafouri‐Fard¹,

Dianatpour²,

Faramarzi³

2018

Klin Onkol

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Background: BRCA1 codes for a tumor suppressor protein involved in DNA repair. Based on the role of single nucleotide polymorphisms (SNPs) in the modification of gene expression and function and the existence of certain SNPs within 3'-untranslated region of BRCA1 with the ability to change bind ing sites for mirRNAs, several association studies have been designed to explore the significance of SNPs within BRCA1 gene in conferr ing breast cancer (BC) risk. This study aims to assess the relationship between BRCA1 SNPs and BC us ing meta-analysis. Aim: To conduct a meta-analysis for retriev ing case-control studies on the associations between the rs11655505, rs1799966, rs3737559, rs1799950, rs799917 and rs16941 BRCA1 polymorphisms and BC. The pooled odds ratios and its 95% confidence intervals were measured us ing fixed and random model to define the association between these polymorphisms and BC risk. Conclusion: No significant association was found for any of these polymorphisms and BC risk in the allelic, homozygote, dominant or recessive models. Over all, our study implies that the mentioned polymorphisms are not associated with BC risk. However, our study did not exclude the possible contribution of other SNPs within this gene in BC nor substantial contribution of multiple variants within this gene in conferr ing BC risk.

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Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer

Cited by 4 publications

References 31 publications

Constitutional Mosaic Epimutations – a hidden cause of cancer?

Constitutional Mosaic Epimutations – a hidden cause of cancer?

Age Distribution of Breast Cancer from a Thailand Population-Based Cancer Registry

Meta-Analysis of BRCA1 Polymorphisms and Breast Cancer Susceptibility

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