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Most cancers are caused by DNA replication errors, landmark study reveals

Friday, March 24th, 2017

Halfway through her HSC, Rachel Woolley suffered exhaustion and a stiff neck.

“All my friends were tired, but it got to the point where I couldn’t get up the stairs,” Ms Woolley said.

Rachel Woolley at home in Sydney. She is a candidate for a bachelor of music at UNSW and is recovering from Hodgkin lymphoma image www.newcures.info

Rachel was diagnosed with Hodgkin lymphoma, a cancer of the lymphatic system.

“It was just completely random,” Ms Woolley said.

“You certainly go through a ‘why me?’ phase. What had I done?” she said.

Now 19, Ms Woolley is studying for her bachelor of music at the University of NSW. Despite the cancer then coming back last year, she was given the all-clear again in January.

What triggered Ms Woolley’s cancer is not known, but a landmark study published on Friday shows that about two-thirds of all cancers are caused by random errors made during normal cell division.

“Our research has broken the paradigm that most cancers are environmental or inherited,” said Assistant Professor Cristian Tomasetti of the Johns Hopkins University school of medicine.

His study with Bert Vogelstein, published in Science, evaluated cancer occurrence in 69 countries, including Australia, covering 4.8 billion people.

Professor Vogelstein said: “Most of the time random mutations during cell division don’t do any harm. That’s good luck.

“Occasionally they occur in a cancer-driver gene. That’s bad luck.”

The study reviewed 32 types of cancer and found that about 66 per cent of cancer mutations result from random DNA copying errors, 29 per cent can be attributed to lifestyle or environmental factors and the remaining 5 per cent are inherited.

Comparative rates of cancer by heredity, random and environmental causes. Most cancers are caused by random errors in DNA replication during cell division. ScienceTomasetti image www.newcures.info

Comparative rates of cancer by heredity, random and environmental causes. Most cancers are caused by random errors in DNA replication during cell division. Photo: Science/Tomasetti

“Detecting cancers earlier can save lives regardless of what caused the mutation,” Assistant Professor Tomasetti and Professor Vogelstein said in a statement. “More research to find better ways to detect cancers earlier is urgently needed.”

The researchers are at pains to say that a cancer is very rarely caused by a single error in cell division, but is often a cumulative process, which is why cancers are more common in older people.

Professor David Thomas is head of the Garvan Institute’s cancer division and director of the Kinghorn Cancer Centre.

“The first Vogelstein study in 2015 was important and heretical. Here they have got a much larger data set that expands to the entire globe.

“I’m not surprised at the ratios of random errors to environmentally-induced mutations and hereditary causes. They seem about right.”

However, Professor Thomas said that in his view some of the assumptions made in the modelling “are very rubbery”, and there will be strong debate about the paper.

Despite his reservations, Professor Thomas said the paper is important: “I do think the broad balance is accurate.”

The overall balance also matches the expectations of Professor Sanchia Aranda, chief executive of the Cancer Council.

“We already know that about one-third of cancers are preventable,” she said. “Very few cancers are truly inherited.”

Professor Thomas said just because most cancers are caused by random mutation, it doesn’t mean environmental factors don’t play a role.

“Even if the bulk of mutations are random, a cell needs to get to the final step to become malignant. Environment and heredity play a role here,” he said.

Assistant Professor Tomasetti said: “Cancer rates vary widely by organ. If you look at lung cancer the concentration is in the environmental component.

“However, with brain cancers, bone cancers or childhood cancers the concentration is in the random component.

“That means virtually all the cancerous mutations are caused by simple mistakes caused by every cell when it divides.”

Is this any comfort to Ms Woolley?

“One perspective is ‘At least I didn’t do anything wrong’,” she said. “But you still feel ‘Why me?'”

Professor Thomas said that while the study was important it won’t change clinical practice.

“The fundamental advice we give as clinicians about how to manage and look out for cancer are not affected by this study.

“People should still try to minimise and manage their exposure to environmental or inherited risk factors.”

While the study won’t immediately impact clinical practice it could assist in the management of the psychological impacts of cancer.

Dr Pandora Patterson is general manager of research at CanTeen, the charity that supports young people living with cancer.

“People digest information in different ways, so it could be helpful to know ‘This is not my fault, it’s just random’,” she said.

Ms Woolley is a member of CanTeen. “By talking to people who have been through all this you can learn stuff that the doctors don’t tell you,” she said.

“It’s such a relief not feeling you’re on your own. You can just sit around with people talking about life – people just get you.”

Her message is that while going through treatment is “very shitty”, things can get better. “It’s really important to stay positive and look forward to the future.”

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Henry Sapiecha

Australia up there with the top 10 healthiest countries in the world, Global Burden of Disease Study Shows

Monday, September 26th, 2016

blue-medical-vector image www.newcures.info

The USA can keep its hoard of Olympic medals. Australia has thrashed the superpower in a far more significant world ranking.

Australia is among the top 10 healthiest countries in the world, according to the most comprehensive analysis of burden of disease and living standards to date.

multi-country-flags image www.newcures.info
Australia is among the top 10 healthiest countries in the world. 

A suite of perfect scores buoyed Australia’s performance, including top marks for indicators associated with war, malnutrition, water access, sanitation and malaria.

Top 30 countries by health-related Sustainable Development Goals
Rank Country
1 Iceland
2 Singapore
3 Sweden
4 Andorra
5 UK
6 FInland
7 Spain
8 Netherlands
9 Canada
10 Australia
11 Norway
12 Luxembourg
13 Ireland
14 Malta
15 Germany
16 Denmark
17 Cyprus
18 Belgium
19 Switzerland
20 Italy
21 Brunei
22 Portugal
23 Israel
24 France
25 Slovenia
26 Greece
27 Japan
28 US
29 Estonia
30 New Zealand
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But its result was dragged down by lower scores for suicide, alcohol, smoking, overweight, HIV, violence and disaster (defined as the death rate due to exposure to forces of nature per 100,000 population).

The US’s comparatively poor performance will come as a surprise to many, considering its socio-economic heft, wrote the research coalition of more than 1870 international researchers who analysed the performance of countries between 1990 and 2015.

The superpower’s lacklustre scores for maternal mortality alcohol consumption, childhood overweight, and deaths due to interpersonal violence, self-harm, and unintentional poisoning compared to other higher income countries dragged down its overall ranking.

East Timor was the biggest success story, winning the title of most improved and rocketing up the rankings to 122nd place.

Dead last was the Central African Republic, with a total SDG index score of 20. War-torn Afghanistan came in 180th place, and Syria fell to 117th, still scoring better than Russia in 119th place. China came was 92nd, and Papua New Guinea 155th.

Overall, the most pronounced progress internationally was among the universal health coverage indicators, largely thanks to anti-retroviral therapies and widespread use of insecticide-treated nets in malaria-endemic countries since the early 2000s.

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And while there were also substantial improvements in childhood stunting caused by malnutrition, childhood overweight rates had worsened considerably over the past 15 years.

“Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient,” the researchers said.

The SDG targets have been a source of intense debate, with critics arguing they were too vague, unrealistic, poorly measured, or missing key indicators – for instance, banning forced labour or mental health improvements.

The SDG agenda replaced the Millenium Development Goal framework, which expired in 2015.

The scores routinely inform decisions concerning which countries may be most deserving of aid funding, as well as national and international policy and strategies.

“The difficulties of measurement are also further compounded by persistent problems of data availability, quality and comparability across a host of indicators” as the researchers work to pull together a daunting tangle of national data sets, survey results and pharmaceutical records.

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Australia’s health indicator perfect scores
Health issue Score /100
Stunting 100
Wasting 100
Malaria 100
Water access 100
sanitation 100
war 100
Neglected tropical disease 100
Household air pollution 100
Skilled birth attendance 100

The latest analysis was a step towards a more cohesive approach to understanding the interaction between SDGs, targets and indicators by comparing the relationship between education, income and fertility, the authors said.

It also raised questions about the impact of other drivers on health and living standards across the globe.

The authors urged governments, donors, and global development institutions to use the results to “enhance accountability through open and transparent review and action”.

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www.ozrural.com.au

Henry Sapiecha