Oligogenic combinations associated with breast cancer risk in women under 53�years of age

Aston, Christopher E.; Ralph, David; Lalo, Dominique; Manjeshwar, Sharmila; Gramling, Bobby A.; DeFreese, Daniele C.; West, Amy D.; Branam, Dannielle E.; Thompson, Linda F.; Craft, Melissa; Mitchell, Debra S.; Shimasaki, Craig; Mulvihill, John J.; Jupe, Eldon R.

doi:10.1007/s00439-004-1206-7

Cited by 44 publications

(41 citation statements)

References 66 publications

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“…By quantitative real time PCR, we could also exclude whole gene deletions in the investigated breast cancer families (results not shown). BARD1 mutations have been proposed to have a lower penetrance [Karppinen et al, 2006] and would affect breast cancer risk together with other genes according to an oligogenic model [Antoniou et al, 2001Ponder, 2001;Pharoah et al, 2002;Aston et al, 2005]. The findings concerning the p.Arg658Cys variant support this assumption.…”

Section: Discussionmentioning

confidence: 79%

Cancer predisposing missense and protein truncatingBARD1mutations in non-BRCA1orBRCA2breast cancer families

et al. 2010

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Fifteen years ago BRCA1 and BRCA2 were reported as high penetrant breast cancer predisposing genes. However, mutations in these genes are found in only a fraction of high risk families. BARD1 is a candidate breast cancer gene, but only a limited number of missense mutations with rather unclear pathogenic consequences have been reported. We screened 196 high risk breast cancer families for the occurrence of BARD1 variants. All genetic variants were analyzed using clinical information as well as IN SILICO predictive tools, including protein modeling. We found three candidate pathogenic mutations in seven families including a first case of a protein truncating mutation (p.Glu652fs) removing the entire second BRCT domain of BARD1. In conclusion, we provide evidence for an increased breast cancer risk associated to specific BARD1 germline mutations. However, these BARD1 mutations occur in a minority of hereditary breast cancer families.

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Section: Discussionmentioning

confidence: 79%

Cancer predisposing missense and protein truncatingBARD1mutations in non-BRCA1orBRCA2breast cancer families

et al. 2010

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“…Öncelikle testlerin yetersizlikleri ve içeriği bireye doğru ve gerçekçi bir tavsiyede bulunabilecek kadar ayrıntılı anlatılmalı-dır. Genomik skorlama ile ilgili bir çalışmada SNP'lerin özelliğinin ve risk skor hesaplama algoritmasının toplum geneline değil, bireye özel olacağı rapor edilmiştir (36). Genomik risk skorlamasındaki başka bir sorun da ilgili SNP'lerin diğer başka birçok yolak ve hastalıkla ilişkili olmasıdır.…”

Section: Genom Boyu İlişkilendirme çAlışmaları (Gwas)unclassified

Coronary artery disease from a perspective of genomic risk score, ethical approaches and suggestions

Ağırbaşlı¹,

Ülman²

2012

Anadolu Kardiyol Derg

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As a leading cause of mortality, coronary artery disease is on the focus of genetic research as a complex trait. Although predictive genetic testing for cardiovascular diseases is on the counter, it is still hard to aggregate information from multiple genetic variants, environmental factors and family history into a single score. Every susceptibility allele provides small contribution to disease formation. Biomarkers play a role in various metabolic pathways. Genetic information and data depend heavily on probabilities. This should be clearly explained by genetic counselor to the patient and relatives who are looking for certain answers. Presence of susceptibility alleles can be a source of anxiety and it may result as a reduced self-confidence in ability to change health behavior. Complex diseases set a new stage to study novel techniques that can elucidate interactions among genetic, environmental and ethnic factors. The cookbook approach to treat a complex disease can often be misleading. Future studies may provide personalized information, which can improve the outcome of standardized treatments. As knowing one's own genetic risk is becoming a task for the responsible individual, it surely will add new challenges to ethical framework. Publicly marketing genetic tests for complex diseases raises ethical concerns. To avoid discriminatory use of genetic information; genetic risk scoring, therapeutic process, ethical policies must have a multifaceted progress. In this review, we summarized the attempts to resolve ethical issues related to genetic testing in complex diseases to resolve patient autonomy with individual responsibility and to aim the patient beneficence and confidentiality. (Anadolu Kardiyol Derg 2012; 12: 171-7)

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“…Common single nucleotide polymorphisms of genes whose protein products are involved in carcinogen and hormone metabolism and/or DNA repair are associated with relative risks of 1.4-2.0; but two and three gene polymorphism combinations may be associated with much higher relative risks (Coughlin & Piper 1999, Feigelson et al 2001, Pharoah et al 2002, Comings et al 2003, Aston et al 2005. The established risk biomarkers serumbioavailable estradiol and testosterone in postmenopausal women (Missmer et al 2004, Tworoger et al 2005, serum insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) in premenopausal women (Hankinson et al 1998), mammographic breast density (Boyd et al 1998) and breast intra-epithelial neoplasia (Page & Dupont 1990; Table 2) have much broader applicability than germline mutations in tumor-suppressor genes.…”

Section: Established Risk Biomarkersmentioning

confidence: 99%

Breast-tissue sampling for risk assessment and prevention

Fabian

Kimler

Mayo

et al. 2005

Endocrine Related Cancer

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Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of shortterm risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and ductal lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in ductal-lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammographic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the method most frequently used for Phase II studies of 6-12 months duration. However, ductal lavage, RPFNA and random and directed core needle biopsies are all being utilized in ongoing multi-institutional Phase II studies. The strengths and weaknesses of each method are reviewed.

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Oligogenic combinations associated with breast cancer risk in women under 53�years of age

Cited by 44 publications

References 66 publications

Cancer predisposing missense and protein truncatingBARD1mutations in non-BRCA1orBRCA2breast cancer families

Cancer predisposing missense and protein truncatingBARD1mutations in non-BRCA1orBRCA2breast cancer families

Coronary artery disease from a perspective of genomic risk score, ethical approaches and suggestions

Breast-tissue sampling for risk assessment and prevention

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