Air pollution may shorten telomers in babies

A study conducted before and after the 2004 closure of a coal-burning power plant in Tongliang, China, found children born before the closure had shorter telomeres than those conceived and born after the plant stopped polluting the air. Telomeres are specialized sections of DNA that allow chromosomes to be faithfully copied during cell division. However, with each round of cell division, telomeres shorten, resulting in a gradual loss of genomic stability. Shortened telomere length has been linked with cancer and heart disease, cognitive decline, aging, and premature death.

Led by Deliang Tang and Frederica Perera at Columbia University's Mailman School of Public Health, the research team analyzed telomere length in the umbilical cord blood of 255 newborns, about half of whom were born before the plant closure and half conceived and born after. In babies born pre-closure, researchers found higher levels of PAH-DNA cord adducts, a biomarker for exposure to polycyclic aromatic hydrocarbons , a toxic component of air pollution from coal plants.

 Elevated levels of these adducts in cord blood were associated with shorter telomeres-the first time this relationship has been tested as well as with lower levels of brain-derived neurotropic factor (BDNF), a protein involved in neuronal grown. However, telomere length was not associated with developmental score in the subset of 210 children tested at age 2, although the researchers say the finding doesn't rule out telomere length-related neurodevelopmental problems at later ages.

Individual's telomere length at birth is known to influence their risk for disease later during adulthood, high levels of air pollution in Tongliang prompted the government to shut down the local coal-burning power plant to improve community health. This action, announced in advance, provided a unique opportunity to compare data on ambient PAH levels, biomarkers, and health outcomes in two successive cohorts of children, with and without prenatal exposure to emissions from the coal-fired power plant.

In previously published research on these cohorts, the authors reported newborns born after the plant closure had lower levels of PAH-DNA adducts, lower rates of various health outcomes, and increased levels of BDNF. The new study adds to the evidence that closing this coal-burning power plant was beneficial to the health and future well-being of newborns there, reducing exposure to air pollution is recommended for pregnant women and infants.
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Single blood test for different types of cancer

The test, called CancerSEEK, is a unique noninvasive, multianalyte test that simultaneously evaluates levels of eight cancer proteins and the presence of cancer gene mutations from circulating DNA in the blood. The test is aimed at screening for eight common cancer types. The use of a combination of selected biomarkers for early detection has the potential to change the way cancer is screen, and it is based on the same rationale for using combinations of drugs to treat cancers.

Circulating tumor DNA mutations can be highly specific markers for cancer. To capitalize on this inherent specificity, researchers sought to develop a small yet robust panel that could detect at least one mutation. The investigators initially explored several hundred genes and 40 protein markers, whittling the number down to segments of 16 genes and eight proteins. They point out that this molecular test is solely aimed at cancer screening and, therefore, is different from other molecular tests, which rely on analyzing large numbers of cancer-driving genes to identify therapeutically actionable targets.

In this study, the test had greater than 99 percent specificity for cancer. "Very high specificity was essential because false-positive results can subject patients to unnecessary invasive follow-up tests and procedures to confirm the presence of cancer," says Kenneth Kinzler, Ph.D., professor of oncology and co-director of the Ludwig Center. The test was used on 812 healthy controls and produced only seven false-positive results.

The test was evaluated on 1,005 patients with nonmetastatic, stages I to III cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung or breast. The median overall sensitivity, or the ability to find cancer, was 70 percent and ranged from a high of 98 percent for ovarian cancer to a low of 33 percent for breast cancer. For the five cancers that have no screening tests -- ovarian, liver, stomach, pancreatic and esophageal cancers -- sensitivity ranged from 69 percent to 98 percent.

A novelty of our classification method is that it combines the probability of observing various DNA mutations together with the levels of several proteins in order to make the final call. Another new aspect of the approach is that it uses machine learning to enable the test to accurately determine the location of a tumor down to a small number of anatomic sites in 83 percent of patients. Although the current test does not pick up every cancer, it identifies many cancers that would likely otherwise go undetected.

To zero in on the analytes they included in their CancerSEEK test, the research team pulled data from more than three decades of cancer genetics research generated at their Ludwig Center at Johns Hopkins, where the first genetic blueprints for cancer were created, as well as data from many other institutions. To precisely determine the optimal number of DNA bases to assess in the CancerSEEK test, the researchers used a method based on diminishing returns. The more DNA bases you assay, the more mutations you are capable of finding, but eventually you reach a point of diminishing returns.

CancerSEEK is noninvasive and can, in principle, be administered by primary care providers at the time of other routine blood work. This has the potential to substantially impact patients. Earlier detection provides many ways to improve outcomes for patients. Optimally, cancers would be detected early enough that they could be cured by surgery alone, but even cancers that are not curable by surgery alone will respond better to systemic therapies when there is less advanced disease.
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