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Singapore Scientists Unravel Cancers Linked To Herbal Remedies

• Joint Singapore-Taiwan research reveals abundant DNA mutations caused by the carcinogen Aristolochic Acid (AA) in a form of kidney cancer.

• AA is a natural compound in Aristolochia plants which have been traditionally used in herbal remedies for weight loss, slimming, and other purposes.

• Scientists find that AA is the most potent carcinogen to date, and may also cause some liver cancers.

• Scientists call for greater public awareness of the dangers of AA in herbal products.

Singapore, 12 August 2013 – A team of scientists from the National Cancer Centre Singapore, Duke-NUS Graduate Medical School Singapore, and Taiwan’s Chang Gung Memorial Hospital, LinKou, have made a breakthrough in understanding the cancer-promoting action of Aristolochic Acid (AA), a natural product of Aristolochia plants traditionally used in some Asian herbal remedies for weight loss and slimming. Using advanced DNA sequencing technologies, the team, led by Professors Teh Bin Tean, See-Tong Pang, Patrick Tan and Steve Rozen discovered that AA is the most potent carcinogen identified to date, causing more DNA mutations than cigarette smoke or ultraviolent light. The team also discovered that besides its previously known contribution to kidney failure and a form of kidney cancer, AA may also contribute to liver cancer. The team identified a "genetic fingerprint" of AA exposure that may pave the way to new approaches to detect AA presence in humans and the environment. The group is also affiliated with the Cancer Science Institute in Singapore, and the Genome Institute of Singapore.

AA is a natural compound found in Aristolochia plants commonly used in traditional herbal preparations for various health problems such as weight-loss, menstrual symptoms and rheumatism. It was officially banned in Europe and North America since 2001 and in Asia since 2003. However, its long-term impact is still being felt as patients with associated kidney failure and cancer are still being diagnosed, especially in Taiwan. In addition, certain AA-containing products are still permitted under supervision and products containing AA are still easily available worldwide, including over the internet.

The potent cancer-promoting activity of AA strongly warrants efforts to restrict the use of AA containing products, including health supplements. "We would like to call for greater public awareness on the adverse health effects of AA. It is therefore important to know the contents of herbal products before one consumes them." said Prof Pang. Reassuringly, in Singapore there is no cause for worry as under the Poisons Act since 1 January 2004, products and herbs sold and supplied in Singapore are not allowed to contain AA and the toxic constituents of Aristolochia herbs.

The Singapore-Taiwan study also reports that carcinogens can leave tell-tale "genetic fingerprints" of their exposure in the DNA of cancer cells, and provides a valuable demonstration of how such fingerprints can be used to identify other cancers not previously associated with that carcinogen. Dr Poon Song Ling, the lead author of the study, said: "AA’s contributions to kidney failure and cancer have been documented, but AA’s possible role in other cancer types was unknown. In this study, we found that the AA-related DNA fingerprint could be used to screen for the potential involvement of AA in other cancers, such as liver cancer." Such findings could lead to a new wave of DNA-based detection systems for monitoring carcinogen exposures in humans and the environment.

This breakthrough came after 1.5 years of intensive research and was published online on 7 August 2013, 2.00pm, U.S. Eastern Time in Science Translational Medicine, a publication that focuses on practical medical advances that result from all stages of translational medicine. The research was supported by grants from the Singapore National Medical Research Council, the Singapore Millennium Foundation, the Lee Foundation, the National Cancer Centre Research Fund, The Verdant Foundation, the Duke-NUS Graduate Medical School Singapore, the Cancer Science Institute of Singapore, the Chang Gung Memorial Hospital, LinKou, the Taiwan National Science Council, and the Wellcome Trust.

For further information, please contact:

Ms Rachel Tan

Assistant Manager, Corporate Communications

Tel: 6236 9535 / 9754 0842

Email: Rachel.Tan.C.H@nccs.com.sg

About National Cancer Centre Singapore

The National Cancer Centre Singapore (NCCS) is dedicated to providing a holistic and multidisciplinary approach to cancer treatment and patient care. We treat almost 70 per cent of the public sector oncology cases. Through developing sub-specialisation among its clinical oncologist, NCC patients receive the best in treatment and care. NCCS is simultaneously engaged in cutting-edge clinical and translational research which has received international recognition. NCCS was accredited by the Joint Commission International in 2010 for quality patient care and safety. NCCS, which is set to be a global leading institution, offers specialist training programmes and research training to local and international applicants.

About NCC Research Fund

The faster we learn more about cancer, the closer we are to a cancer-free future. Hence, the NCCS set up the NCC Research Fund in 2005 to serve as its flagship fundraising and grant-making channel to provide for an array of translational and clinical research programmes. Some of these improve the early diagnosis of cancer, develop and evaluate new treatments to ensure that they can be used safely and effectively on patients, and establish ways to prevent recurrences. Medical breakthroughs as well as remarkable diagnosis, care and treatment advancements that lead to more lives saved, better outcomes and quality of life for patients today are results from years of research.

The Fund is registered under the Charities Act as an Institution of Public Character (IPC) with an independent Board of Trustees. The fund provides (1) seeding funds to help kick-start worthy and emerging research projects; (2) bridging funds between grant cycles when the need arises, and enabling our scientists to work with productive momentum; as well as (3) advancement funds to enhance research related infrastructural capabilities, hardware, tools and processes.

About Duke-NUS Graduate Medical School Singapore

The Duke-NUS Graduate Medical School Singapore (Duke-NUS) was established in 2005 as a strategic collaboration between the Duke University School of Medicine, located in North Carolina, USA and the National University of Singapore (NUS). Duke-NUS offers a graduate entry, 4-year M.D. (Doctor of Medicine) training program based on the unique Duke model of education, with one year dedicated to independent study and research projects of a basic science or clinical nature. Duke-NUS also offers M.D/PhD and PhD programs. As a player in Singapore's biomedical community, Duke-NUS has identified five Signature Research Programs: Cancer & Stem Cell Biology, Neuroscience and Behavioural Disorders, Emerging Infectious Diseases, Cardiovascular & Metabolic Disorders, and Health Services and Systems Research.

Duke-NUS and SingHealth, Singapore’s largest public healthcare group, have established a strategic partnership in academic medicine. This initiative will guide and promote the future of medicine, tapping on and combining the collective strengths of SingHealth's clinical expertise and Duke-NUS' biomedical sciences research and medical education capabilities. For more information, please visit www.duke-nus.edu.sg

About Chang Gung Memorial Hospital

The Chang Gung Memorial Hospital (CGMH) is the largest health care system in Taiwan and a non-profit organization founded in 1976. It has two academic medical centers (located in LinKou and Kaohsiung) and five teaching hospitals (located in Keelung, Taipei, Taoyuan, ChiaYi, and Yunlin) with nearly 10000 beds. CGMH is a world leading hospital that provides highest quality medical services to the local and international community, and actively engaged in innovative medical research. As a biggest hospital system, CGMH treats nearly 25 per cent of all cancer patients in Taiwan. In 2014, CGMH LinKou branch will open its proton therapy center to the public, which is the first treatment center of its kind in Asia except Japan. For detail information, please visit: www.chang-gung.com or www.cgmh.org.tw

About Cancer Science Institute of Singapore

The Cancer Science Institute of Singapore (CSI Singapore) was officially launched on 15 October 2008. CSI Singapore aims to position Singapore as a global-leader in the field of Biomedical Sciences. Its mission: to conduct a multifaceted and coordinated approach to cancer research, extending from basic cancer studies all the way to experimental therapeutics and in so doing improve cancer treatment.

CSI Singapore is a state-of-the-art university research institute affiliated with, and hosted at the National University of Singapore. In 2008, it was awarded a $172 million "Research Center of Excellence" grant, one of only five in Singapore, by the National Research Foundation and the Ministry of Education.

The institute is an anchor for research expertise in two broad programmes: Cancer Biology & Stem Cells, and Experimental Therapeutics. These programmes form expansive platforms for CSI Singapore’s focus on key cancer disease cancers in gastric, liver, lung and leukemia which are endemic in Asian populations.

About Genome Institute of Singapore

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has 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.

www.gis.a-star.edu.sg

Reference Materials:

Annals of Internal Medical, The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy