Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

International multi-centre research group finds genetic defect contributing to cancer susceptibility

08.02.2007
Gene elevating breast cancer risk also causes prostate cancer

An international multi-centre research effort has identified a new genetic defect as a potential heritable breast cancer susceptibility candidate. The same PALB2 mutation also seems to in some measure cause prostate cancer.

Cancer is a complex and common disease caused by a combination of both genetic and environmental factors. An inherited predisposition seems to be involved in at least 5–10 per cent of all cases of breast cancer. The two major familial breast cancer susceptibility genes BRCA1 and BRCA2 only explain 20-30 per cent of families with site-specific female breast cancer, which suggests the contribution of additional susceptibility genes. According to Dr Robert Winqvist, who coordinates the research effort, the identification of these genes may help to clarify the genetic background contributing to breast cancer and suggest novel pharmaceutical targets. It could also lead to genetic screening that identifies individuals at increased breast cancer risk and result in improved prevention efforts and treatment.

About a year ago, Dr Bing Xia and Professor David Livingston at the Dana-Farber Cancer Institute in Boston identified a novel BRCA2 binding factor, PALB2 that regulates certain key functions of normal BRCA2 activity. The next step was to set out to evaluate the newly detected PALB2 gene as a potential heritable breast cancer susceptibility candidate by screening for disease-related alterations. The results of this international research effort were recently published in Nature.

The research first involved comprehensive screening for genetic aberrations in 113 Finnish breast cancer families. The same constitutional mutation in PALB2 was observed in three families. It was later showed that the relevant mutant protein is deficient in its ability to support the kinds of DNA damage responses in which PALB2 normally participates. The mutation was further also investigated in 1,918 specimens from an unselected series of Finnish breast cancer individuals. This study revealed 18 mutation-positive individuals, about one per cent of the studied patients, most of whom turned out to have a familial pattern of disease development. The study also involved 141 unselected male breast cancer patients, 188 familial and 288 unselected colorectal cancers, as well as 164 familial and 475 unselected prostate cancer patients. In prostate cancer, one multigenerational cancer family was found where cancer occurred in several generations and all patients showed the single mutation in PALB2 that was studied. According to Winqvist, this suggests that this Finnish founder mutation may be important in heritable prostate cancer as well. Male breast cancer and colorectal cancer cases did not display the mutation.

The constitutional mutation elevates the risk of breast cancer four-fold

"Present results show that the discovered PALB2 mutation elevates the risk of breast cancer four-fold. However, we still need more research to better assess the effect on cancer development. As the comprehensive mutation analysis was originally conducted on only 113 cancer families, it may be that there still are other PALB2 genetic defects accounting for heritable breast and prostate cancer susceptibility. Recent results also imply that PALB2 might be a cancer susceptibility gene in other populations as well. It's been shown that two of the mutations identified in Fanconi anemia patients in non-Finnish populations seem to be associated with familial breast cancer," says Winqvist.

Winqvist points out that, in spite of recent advances, known factors can only explain a fraction of heritable susceptibility to breast cancer. He is nonetheless disposed to believe that the evaluation of yet other biologically significant factors will in time improve the situation. "Hopefully, increased knowledge of underlying mechanisms will provide better conditions for cancer prevention, diagnostics and treatment," Winqvist says.

The multi-centre research involved researchers from Oulu, Tampere, Kuopio and Helsinki Universities or university hospitals in Finland as well as from the US National Cancer Institute. The other research coordinator was Professor David Livingston from Boston. The discovery of the PALB2 genetic mutation was made by HanneleErkko, a PhD student in the Winqvist laboratory, who also carried out a number of the genetic analyses that followed. Dr Xia from the Livingston team was in charge of key analyses to prove the biological significance of the mutation.

The funding bodies behind the research include the Academy of Finland, the Foundation for the Finnish Cancer Institute, the Northern-Ostrobothnia Health Care District and the University of Oulu as well as by the US National Cancer Institute NCI.

The article was published in Nature on 8 February.
Nature online DOI: 10.1038/nature05609

Niko Rinta | alfa
Further information:
http://www.aka.fi

Further reports about: Cancer Mutation PALB2 Winqvist multi-centre prostate cancer susceptibility

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>