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 Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>