Use of association studies to define genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers

@article{Hughes2008UseOA,
  title={Use of association studies to define genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers},
  author={David J. Hughes},
  journal={Familial Cancer},
  year={2008},
  volume={7},
  pages={233-244}
}
  • D. Hughes
  • Published 19 February 2008
  • Biology
  • Familial Cancer
Though much progress has been made in understanding the role of two major high-risk breast cancer (BC) susceptibility genes, BRCA1 and BRCA2, it remains unclear what causes the observed variation in risk between mutation carriers. This marked variability in individual cancer risk both between and within BRCA1 and BRCA2 mutation carrier families may be partly explained by modifier genes that influence mutation penetrance. Defining these modifiers should help refine individual cancer risk… 

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References

SHOWING 1-10 OF 107 REFERENCES

Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history.

The hypothesis that pathways involving endocrine signaling, as measured through AIB1 genotype and reproductive history, may have a substantial effect on BRCA1/2-associated breast cancer risk is supported.

BRCA1 wild-type allele modifies risk of ovarian cancer in carriers of BRCA1 germ-line mutations.

  • Sophie M. GinolhacS. Gad O. Sinilnikova
  • Biology
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  • 2003
The results of this study imply that a quite significant proportion of the interindividual variability in ovarian cancer penetrance in BRCA1 carriers may be explained by a common BRCa1 Gly1038 wild-type allele, given its high frequency.

Common BRCA2 variants and modification of breast and ovarian cancer risk in BRCA1 mutation carriers.

  • D. HughesSophie M. Ginolhac O. Sinilnikova
  • Biology
    Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
  • 2005
It is concluded that if these single-nucleotide polymorphisms do modify the risk of cancer in BRCA1 mutation carriers, their effects are not significantly larger than that of N372H previously observed in the general population.

Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene

The results strongly suggest that contrary to previous studies, there is no significant effect of AIB1 genetic variation on BC risk in BRCA1 mutation carriers and provide an indication that there is also no strong risk modification in B RCA2 carriers.

CGH-targeted linkage analysis reveals a possible BRCA1 modifier locus on chromosome 5q.

The results suggest the presence of one or more genes on chromosome 5q33-34 that modify breast cancer risk in BRCA1 mutation carriers, which may be utilized to identify penetrance modifiers in other autosomal dominant syndromes.

A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability

A common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group.

Variation in cancer risks, by mutation position, in BRCA2 mutation carriers.

Cancer occurrence in 164 families with breast/ovarian cancer and germline BRCA2 mutations was studied to evaluate the evidence for genotype-phenotype correlations. Mutations in a central portion of

CAG and GGC repeat polymorphisms in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers

It is concluded that, in contrast to previous observations, if there is any effect of the AR repeat length on BRCA1 penetrance, it is likely to be weak.

The RAD51 135 G>C Polymorphism Modifies Breast Cancer and Ovarian Cancer Risk in Polish BRCA1 Mutation Carriers

The results reveal that women who harbor the C allele have almost twice the reduction in breast and ovarian cancer risk compared with women who Harbor only the G allele, suggesting that the effect of the RAD51 C allele is an important risk modifier for malignancies occurring on a background of BRCA1 mutations.

Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers

The role of allele variants 677T and 1298C and 2756G has been investigated as potentially modifying factors of BRCA gene penetrance, evaluated as age at first diagnosis of cancer, in 484 BRCa1/BRCA2 carriers and in 108 sporadic breast cancer cases as a control group.
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