Tuesday, October 25, 2011

Today's lifestyles, tomorrow's cancers: trends in lifestyle risk factors for cancer in low- and middle-income countries

Abstract

Background: The global burden of cancer is projected to increase from 13.3 to 21.4 million incident cases between 2010 and 2030 due to demographic changes alone, dominated by a growing burden in low- and middle-income countries (LMICs). Lifestyle risk factors for cancer are also changing in these countries and may further influence this burden.

Design: We consider examples of changes already occurring in population-level distributions of tobacco and alcohol consumption, body weight, and reproductive lives of women to gauge the magnitude of their projected impact on cancer incidence in future decades.

Results: Trends in lifestyle factors vary greatly between settings and by sex. Some common trends point to considerable increases in cancers of the (i) lung in men due to tobacco smoking; (ii) upper aerodigestive tract (UADT) due to increasing tobacco and alcohol consumption, worse in men; (iii) colon from increasing body mass index, and alcohol and tobacco consumption; and (iv) in women, breast due particularly to consistent international trends of younger age at menarche, smaller family size, and, at postmenopausal ages, increasing body weight.

Conclusions: In many LMICs, the future cancer burden will be worsened by changing lifestyles. Affected common cancer sites likely to experience the largest increases are lung, colon, UADT, and breast.

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Existing Technique Can Detect Fetal Genetic Abnormalities in Maternal Blood


Non-invasive procedure could make prenatal testing easier, but it comes with ethical problems.

Until last week, scrutinizing a fetus's DNA for indications of genetic abnormalities meant tapping into the mother's womb with a needle. Now there's a test that can do it using a small sample of the mother's blood. MaterniT21, a Down's syndrome test that Sequenom of San Diego, California, launched in major centres across the United States on 17 October, is the first of several such tests expected on the market in the next year. It signals the arrival of a long-anticipated era of non-invasive prenatal genetic screening, with its attendant benefits and ethical complications.

With the technology in place to sequence the fetal DNA carried in a pregnant woman's bloodstream, geneticists predict the list of conditions that can be detected by non-invasive means will grow rapidly. Another company, Gene Security Network of Redwood City, California, says its forthcoming test will also check for other genetic abnormalities, and Sequenom is studying the feasibility of expanding its test.

"There's every reason to think that in the future you'll be able to extract an enormous amount of information from that sequencing data," says Peter Benn, director of the Diagnostic Human Genetics Laboratories at the University of Connecticut Health Center in Farmington.

Sequenom's test sequences 36-base-pair fragments of DNA to identify sections from chromosome 21. Normally, the chromosome contributes 1.35% of the total maternal and fetal DNA in the mother's blood. An overabundance of this material indicates the genetic abnormality that marks Down's syndrome.

Sequenom is marketing its test as an add-on to current screening methods, which estimate the chance that a woman is carrying a fetus with Down's syndrome from ultrasound results and protein markers in the blood. Such non-genetic screening can detect 90–95% of Down's syndrome cases, but falsely indicates that up to 5% of women are carrying a baby affected by the condition. Sequenom's test could be taken after a positive screening result to help a woman decide whether to undergo amniocentesis, a test that extracts amniotic fluid with a needle and carries a small risk of miscarriage. A study published this month, and paid for by Sequenom, found that the company's test has a false positive rate of 0.2% (G. E. Palomaki et al. Genet. Med. http://dx.doi.org/10.1097/GIM.0b013e3182368a0e; 2011).

It could spare some women from having amniocentesis after a false-positive screening result. But Benn says that the test will also pose difficulties. For instance, because it would take 8–10 days to get the results of Sequenom's test, if a woman did still opt for amniocentesis, and the result confirms that the baby has Down's syndrome, there would be little time left to decide whether to terminate the pregnancy. And some women who test positive on MaterniT21 will probably choose to terminate pregnancies immediately rather than have amniocentesis.

"Inserting this new test in the way that Sequenom is proposing is very difficult, from the patient perspective, and difficult for physicians and counsellors to manage," Benn says.

Ethicists also caution that using such easy screening methods ever earlier in pregnancy might worsen the gender imbalance seen in countries such as China and India. And if it becomes routine to check for many different kinds of genetic abnormalities, ethicists predict that more couples may face the quandary of whether to carry an 'unhealthy' fetus to term.

"The idea that couples have choices about whether to continue their pregnancies may become strained because parents may be seen as irresponsible for allowing 'defective' pregnancies to go to term," says Mildred Cho, an ethicist at Stanford University in Palo Alto, California. Other ethicists worry that fears of eugenics will be raised if testing can be done for less-serious conditions.

Sequenom is solely focused on developing tests for conditions that are already part of prenatal screening programmes, says Mathias Ehrich, the company's senior director for research and development diagnostics. "We do not want to invent new applications. Our focus is on making existing clinical applications safer," he says. "I don't think that we are in a position to say that we should determine what hair colour the baby has."