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A12 Monday, February 3, 2014



LAB REPORT ...........................................


In a mammoth mission to understand cancer, scientists around the globe are joining forces to genetically map the deadly disease, writes David Tan


cientists have been studying cancer for decades. Yet the more the disease is studied, the more researchers discover what they don’t know. But in recent years, scientists around the globe have joined forces to tackle cancer, steadily making progress in unravelling its complexity. According to Globocan 2012, a report by the World Health Organisation’s International Agency for Research on Cancer, there were 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer (within five years of diagnosis) in 2012 worldwide. Unless we understand this disease better, the WHO expects there to be 19.3 million new cancer cases per year by 2025. One thing almost all cancers do is change our genetic blueprint, or genome. These changes disrupt biological pathways, causing cells to grow uncontrollably. This process is often specific to a particular type or stage of cancer, so scientists have been mapping the genetic changes in each cancer.

To perform this herculean task researchers around the world are combining efforts. In 2008, the International Cancer Genome Consortium (ICGC) was formed to deliver genomic data on more than 50 types of cancer in 10 years. With its global reach, the consortium has been one of most ambitious biomedical research efforts since the Human Genome Project, a mammoth mission by the US Department of Energy and the National Institutes of Health that ran from 1990 to 2003. Crucially, the ICGC makes its data rapidly and freely

From left: Associate Professor Steve Rozen, Professor Teh Bin-tean and Professor Patrick Tan. Below, the fourth ICGC Scientific Workshop in 2010 in Couran Cove, Australia.

available to the global community. “Clearly, there is an urgent need to reduce cancer’s terrible toll,” said Dr Thomas Hudson, of the Ontario Institute for Cancer Research in Canada and member of the ICGC Secretariat, at the consortium’s launch. “To help meet that need, the consortium will use new genome analysis technologies to produce comprehensive catalogues of the genetic mutations involved in the major types of cancer.” Five years on, these efforts are starting to bear fruit. In particular, research from Asia is providing insight into ethnic-specific differences in common cancers. China, a founding member of the ICGC, launched a gastric cancer project in 2008. The Chinese Cancer Genome Consortium’s (CCGC) collaborative projects draw on data from 19 hospitals and institutes in 12 cities. It includes more than 200 researchers using nextgeneration genetic sequencing and bioinformatics to mine genetic and lifestyle differences between Caucasian and Asian cancer patients. Cancer causes nearly a quarter of all deaths in China and is now the leading killer in the

Clearly, there is an urgent need to reduce cancer’s terrible toll DR THOMAS HUDSON, ONTARIO INSTITUTE FOR CANCER RESEARCH

country. About 2.7 million people are diagnosed with cancer annually and 1.9 million people die of the disease. Dr Yang Huan-ming, chief co-ordinator of the CCGC, says: “We believe that more genomic data from Asian cancer patients will augment the work of existing ICGC cancer projects and promote progress towards making cancer a manageable condition.” The CCGC focuses on cancer types that are more common in China than the rest of the world: gastric, esophageal and liver cancers occur more than twice as often, while nasopharyngeal cancers occur 70 per cent more often in China than worldwide. The Chinese team is comparing its data with projects in France, Japan, Britain and the US. “Researchers using this data will have greater opportunities to deliver more precise diagnostic tests for the clinical management of patients in China and around the world,” says Dr Lu You-yong, director of the Laboratory of Molecular Oncology at Beijing Cancer Hospital. Hong Kong has also been contributing to the international consortium. Professor Joseph Hun-wei Lee, vice-president for research and graduate studies at the Hong Kong University of Science and Technology (HKUST), sits on the ICGC’s executive committee. “Our participation in the ICGC provides a platform for Hong Kong researchers to maintain a close working relationship with the international cancer genomics research community and participate in the advancing frontier of cancer genomics,” says Lee. “Research on Hong Kongspecific cancers need to be presented and discussed

Professor Joseph Hun-wei Lee of the ICGC’s executive committee. throughout the scientific and medical community.” Through the ICGC, researchers from different Hong Kong institutions – including HKUST, University of Hong Kong, Chinese University and the Hong Kong Brain Cancer Genome Consortium – have been collaborating. These efforts bring together oncologists, biochemists, engineers, bioinformaticians and statisticians to work on various projects, such as studies into cancer genomics and psychotic disorders. Professor Xue Hong, director of the HKUST Applied Genomics Centre, is a member of the ICGC’s Technology Working Group and Pan-Cancer Analysis Group. She says one of the main research areas for the Hong Kong team in the international consortium is brain metastatic cancers. These conditions often originate from lung and breast cancers, and are more likely to cause death compared to the primary cancers. “In view of the high incidence of lung cancer in Hong Kong, decoding the mechanism of lung to brain metastasis of cancer is a topic of societal, as well as scientific, importance,” says Xue. Cholangiocarcinoma is a cancer involving uncontrolled growth of the bile ducts – the part of the liver that drains the digestive juice bile into the intestine. In most countries, the cancer is rare. However, in northeast Thailand and Laos it is widespread because patients are exposed to parasites called liver

flukes. Cholangiocarcinoma patients have a dismal prognosis with a five-year survival rate of only 5 per cent. In Singapore, a team of ICGC scientists from the National Cancer Centre and Duke-NUS Graduate Medical School recently collaborated with colleagues in Romania and Thailand. Using advanced DNA sequencing to map all the genes disrupted in cholangiocarcinoma, they identified several genes that were repeatedly disrupted in the development of the disease. BAP1 is one gene that participates in the unpacking of DNA, known as chromatin modification. Drugs targeting this process, called chromatin modifier drugs, are now being developed. “While further research needs to be done, this may pave the way for identifying which bile-duct cancer patients may benefit from chromatinmodifier drugs,” says Professor Teh Bin-tean, one of the study’s lead researchers. Findings from the study also revealed clues as to how the cancer develops. “A poorly-understood question in cancer research is whether different carcinogens [cancer-causing chemicals] applied to the same cancer type will cause disruptions in the same sets of genes, or if different carcinogens will cause different types of genes to be disrupted,” says co-lead researcher Associate Professor Steve Rozen. To answer this question, the researchers looked at cholangiocarcinomas from Thailand, Singapore and Romania. While the cancers appeared similar under the conventional microscope, at the molecular level they were, in fact, very different. This means that even though the carcinogens were acting on the same organ, exposure to various carcinogens likely caused disruptions in different sets of genes. Co-lead researcher Associate Professor Patrick Tan says: “Based on these results, it may be possible to investigate a patient’s cancer and, by looking at the types of disrupted genes, infer what caused the cancer.”

Jeanette Wang

Are we overusing IVF? As the use of in vitro fertilisation (IVF) expands to a wider range of fertility problems, experts warn that the risks could outweigh the benefits. In an article published on the British Medical Journal website, a team led by Dr Esme Kamphuis from the University of Amsterdam’s Centre for Reproductive Medicine argue that the evidence underpinning the use of IVF for some newer indications – such as unexplained fertility – is weak, and they question whether IVF is equally effective in these conditions and if the long-term health risks for IVF children can be justified. Unexplained infertility accounts for up to 30 per cent of all couples presenting for IVF, many of whom will conceive when not treated immediately. Extended use of IVF increases the risk of harm, say the authors. Multiple pregnancies are associated with complications for mothers and infants. Children born through IVF may have higher blood pressure, body fat distribution, glucose levels and more generalised vascular dysfunction than children conceived naturally.

What’s your earliest surviving memory? It’s known that memory lapses with age, but a new study has found that age seven is when one’s earliest memories – events that happened before age three – tend to be forgotten. The phenomenon is known as childhood amnesia. Psychologists at Emory University in Atlanta, in the US, interviewed and recorded 83 three-year-old children while their parents asked them about six events that the children had experienced in recent months, such as trips to the zoo or birthday parties. The psychologists followed up with the children between the ages of five and nine; they were asked to recall events they had recounted at age three. While the children between the ages of five and seven could recall 63 to 72 per cent of the events, the children who were eight and nine remembered only about 35 per cent. Young children tend to forget events more rapidly than adults because they lack the strong neural processes required to bring together all the information that goes into a complex autobiographical memory, explains lead researcher Patricia Bauer. The research was published in the journal Memory.

Losing sight of the dangers of beauty contact lenses ................................................ Bhavna Sakhrani The dreamy, doe-eyed appearance, popularised by stars from the likes of Lady Gaga to Japanese and South Korean celebrities, has become a mainstream beauty fad in across Asia. Increasingly, people are turning to beauty contact lenses, which make eyes appear brighter and larger, to achieve this wide-eyed look. But recent research from Polytechnic University’s School of Optometry suggests that beauty could come with a price – in the form of eye infections, injuries and even loss of vision. “There has been a sudden increase in the popularity of coloured contacts on the

market, especially the limbal ring lenses that enhance the shape of the eye. Usage has almost doubled in the last year [in Hong Kong],” says lead researcher Professor Pauline Cho. “It is very alarming as we’ve seen a number of reports of people misusing these lenses.” The study compared the levels of microbial adhesion in coloured contact lenses, which have surface, embedded or sandwiched pigments. A total of 15 brands – bought online, from optical shops and consignment counters – were tested by researchers. Only two of the brands tested passed the standardised labbased rub-off test, indicating that most lenses contained surface pigments that could easily rub off.

Using contact lenses as fashion accessories is risky.

Of the remaining 13 brands, when challenged with microorganisms, the levels of microbial adherence to the lenses were at least six times higher than the brands that passed the test. This means that coloured contact lenses with surface pigments allow more adhesion of micro-organisms and can attract more deposits. “This is not to say that coloured contact lenses with surface pigments are not safe, but that lenses with surface pigments allow more adhesion of micro-organisms if it can be easily rubbed off,” says Cho. “If pigments are reliable and approved by the US Food and Drug Administration, it should not cause any harm to the eye, but you must know where they come from and if they are safe.”

In Hong Kong, as there is little regulation of the sale of contact lenses, the public can easily purchase lenses online and from unlicensed cabinet stores. Many unauthorised dealers claim to use safe surface pigments or pigments that are embedded in the contact lens. Cho advises consumers to buy lenses only from an authorised optometrist. “In Hong Kong, we do have legislation on prescribing contact lenses. People should not view contact lenses just as a fashion accessory; it is actually a medical device. If you want to use them, it can be safe, provided you go through the appropriate procedures.” Users of all contact lenses, coloured or not, should be first examined by a registered

optometrist. A licensed practitioner can also guide consumers on proper fitting and give instructions on usage. Cho cautions that improperly fitted lenses, or lenses sold on the internet or from street vendors, can result in serious damage including scratches on the cornea, corneal infection, conjunctivitis and, in serious cases, loss of vision. If they are sourced from a professional contact lens practitioner, they can usually be trusted, says Cho. Occasional users whose eyes are not adjusted to contact lenses should refrain from using them for more than four hours, Cho adds. If contact lenses are not properly stored, or if people sleep with contact lenses in, the health of the eyes can be compromised.

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