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Rare cancer-causing syndrome found, for the first time, in Singapore

Findings from the AACR Centennial Conference on Translational Cancer Medicine: From Technology to Treatment Singapore, Nov. 4-8, 2007

A rare hereditary disorder that strongly predisposes carriers to develop cancer at an early age has been found in an Asian female, report researchers today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine.

Generally, a person should have two normal copies of the powerful p53 tumor suppressor gene. But in the disorder known as Li-Fraumeni syndrome (LFS), one defective copy of p53 is inherited from a parent. Only about 400 families worldwide are known to have LFS, but none had been found in Singapore before this study, say researchers from the National Cancer Centre Singapore.

Although LFS is rare, it was found in a woman who had developed early onset breast cancer. Therefore, clinicians should also consider LFS as a potential diagnosis in young women with breast cancer, say the study investigators, Ann S.G.Lee, D.Phil., of the Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, and Peter Ang, M.Med., of the Department of Medical Oncology, National Cancer Centre Singapore.

“In a selected population of young breast cancer women with a family history suggestive of LFS, genetic testing may help to identify the syndrome,” said Lee. “Since LFS greatly increases the risk of developing several types of cancer, it would be important if it could be identified early. This would help persons at risk decide on certain health surveillances and other measures that might improve their long term health.”

People with LFS are at increased risk for developing multiple primary tumors of many different origins. In cancer patients who do not have LFS, cancer normally “knocks out” the normal function of p53 in order to grow and metastasize. But when a person only has one working copy of the gene to begin with, the chance that cancer will develop increases significantly, Lee says.

The prevalence of LFS in Singapore is unknown. Because one of the research interests of the National Cancer Centre Singapore is breast cancer susceptibility, investigators there decided to look for evidence of the syndrome in women who developed breast cancer at 35 years of age or younger. About four percent of breast cancer in Singapore is found in younger women, researchers say.

They recruited 30 patients and their families, took detailed family histories and tested their blood for mutations in the p53 gene and the CHEK2 gene, another tumor suppressor gene found to be mutated in some patients with LFS.

They found LFS in one woman in Singapore who had been diagnosed with breast cancer at age 25. Her mother had been diagnosed with breast cancer at age 34, and died at age 35, and a sister died of a brain tumor when she was 10 years old. The patient’s non-identical twin sister, determined by DNA fingerprinting, does not have LFS and does not have the p53 mutation found in her affected twin.

The researchers add that establishing a detailed family history that extends back for three generations, which is necessary to make a diagnosis of LFS, can be problematic. “In Singapore, many families are small and many are migrants, and it can be difficult to obtain the needed history,” Lee said. “That is why we focused our study on young onset breast cancer patients and tested these individuals for germ-line mutations in the p53 gene.”

The study was funded by the SingHealth Cluster Research Fund and the National Medical Research Council of Singapore.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The Agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Staci Vernick Goldberg | EurekAlert!
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