Germline copy number variations and cancer predisposition
Ana Cristina Victorino Krepischi1, Peter Lees Pearson, Carla Rosenberg
1CIPE, AC Camargo Hospital, São Paulo, Brazil.
Future Oncology (London, England)
|April 21, 2012
Summary
Germline copy number variations (CNVs) are linked to inherited cancer risk. While rare, high-penetrance CNVs contribute to familial cancers, common low-penetrance CNVs may collectively increase cancer predisposition in the general population.
Area of Science:
- Genetics
- Oncology
- Cancer Research
Background:
- Germline copy number variations (CNVs) are a significant source of genetic diversity.
- The precise mechanisms by which CNVs influence cancer susceptibility are not fully understood.
- While numerous highly penetrant genes causing inherited cancer predisposition are known, their contribution to familial cancers is limited.
Purpose of the Study:
- To provide an overview of the role of germline CNVs in cancer predisposition.
- To highlight the association between rare CNVs and known cancer predisposition genes.
- To discuss the potential impact of low-penetrance CNVs on population cancer risk.
Main Methods:
- Review of existing literature on germline CNVs and cancer predisposition.
- Analysis of the overlap between known Mendelian cancer genes and observed CNVs.
- Synthesis of evidence regarding the penetrance and frequency of different types of CNVs.
Main Results:
- Nearly half of the genes associated with Mendelian cancer predisposition have also been identified as rare CNVs.
- Highly penetrant alleles, including rare CNVs, account for less than 5% of all familial cancers.
- Common low-penetrance CNVs, though individually modest contributors, collectively impact cancer predisposition.
Conclusions:
- Most genetic cancer risk in the general population likely involves genes with low or moderate penetrance.
- The combined effect of common low-penetrance CNVs is crucial for estimating overall cancer risk.
- Further research into the role of germline CNVs is essential for understanding cancer susceptibility.
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