Posts Tagged ‘biomarkers’
More than a billion people worldwide smoke tobacco. With a 20-fold greater risk of developing lung cancer than nonsmokers, plus increased risks of other types of cancers, choosing to smoke represents the most significant carcinogenic exposure confronting public health professionals today. A recently completed study published in Nature (se below) reports on the sequencing of DNA from a small-cell lung cancer victim. Tobacco smoke deposits hundreds of chemicals in an individual’s airways and lungs including numerous mutagens. The investigators have used massively parallel sequencing to illuminate the distinctive mutations associated with exposure to cigarette smoke carcinogens, as well as the signature of DNA repair activities.
The investigators didn’t speculate about the policy implications of this work, but things that come to mind for me include better early detection of pre-cancerous conditions, genomic therapies that intervene on a macromolecular level and an airtight method for denying someone health insurance coverage for lung cancer treatment because of self-inflicted tobacco carcinogenesis.
One of the worrisome statements made in the discussion section was that, on average, lung cancer develops after 50 pack-years of smoking (where a pack-year is 7,300 cigarettes, representing the number smoked in a pack a day for a year), or an average of one mutation for every 15 cigarettes smoked, which could potentially transform a normal cell into a cancerous one that eventually clones into a tumor.
There are a couple of epidemiological modeling papers cited for that conclusion that should be looked in on later, but the 50 pack-years assessment provoked a bit of an oh-shit moment, because if I’m understanding the number properly, 50 pack-years is around a pack a day for one year; the dose-response relationship is cumulative, so the same risk would be associated with half a pack a day for two years, and so forth. Tobacco contains a lot of other carcinogens other than mutagens, which initiate a carcinogenic response; these other carcinogens are promoters, which accelerate the growth and development of a tumor. So, even if you’ve only currently a “light” smoker, you’re probably still screwing yourself health-wise; even if you quit years ago, you may have macromolecular or cellular injury now, that will eventually turn into lung cancer, but it just hasn’t progressed to the that you’re experiencing adverse effects. It’s just another reason for not smoking at all or stopping at the earliest instance possible, in order to preserve your health (and insurance).
Pleasance, E.D. et al. 2009. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature. 463, 184-190 (14 January 2009) http://www.nature.com/nature/journal/v463/n7278/full/nature08629.html
Well, maybe a few. Such as the quote from the West Virginia woman. . .
How can we get digital cable and Internet in our homes, but not clean water?
. . . after having to treat her kid for skin lesions because he’s bathed in water contaminated with nickel, or get crowns on the teeth of another kid of hers after metals-contaminated drinking water has eroded the enamel off the kid’s teeth.
How about, “because we care more about digital cable and Internet than clean water”. How about, “because we’ve learned to not think of clean water as a right that we have to continue to fight for”. How about “because the political will which was around 40 years ago to give us the Clean Water Act and the Safe Drinking Water Act is has disappeared”. How about, “because we abrogate this responsibility for our health, leaving it in the hands of politicians and bureaucrats”.
The tone of the New York Times article implies that the government should be doing more, such as more stringent enforcement, or beefing up the resources of regulatory agencies. Helpfully, the article provides a database that allows readers to identify violations of Clean Water Act or Safe Drinking Water Act regulations in their area. There are similar products available from EPA such as EnviroFacts and the TRI database. However these all reflect operational and management metrics – how many permit violations have occurred or how many pounds of chemicals are emitted – which don’t really say anything about environmental conditions or the risks encountered by humans or the ecosystem. These still reflect the “command and control” style of environmental management which some in EPA through the Unfinished Business and Reducing Risk reports were considering to be obsolete as long as 20 years ago. Not addressed in the New York Times article is the idea that the existing command and control regulatory structure developed in the 1970s and 1980s NPDES, RCRA, Clean Air Act permitting and enforcement – is broken.
There is some recognition that a new framework for environmental protection is needed, which acknowledges that health and ecological risks are related to where a community is located, that multiple and overlapping sources of contaminant releases might affect members in that community, and that the best measure of risk is based on what types and levels of contaminants those individuals are exposed to. EPA has developed frameworks for community-based risk assessment and cumulative risk assessment, which acknowledge:
In many cases, human health often is directly related to where one lives. Certain communities, groups, or individuals within a community may be more at risk than others from multiple exposures to chemicals based on the location of a town; the individual’s location within a town; activities, such as commuting to work or school or exercising; dietary patterns of residents; or socioeconomic status. Focusing on the community provides a rational starting point for developing, evaluating, and applying cumulative risk tools to determine the risk of chemical mixtures.
Of course, characterizing risks with this framework involves more monitoring, particularly from the locations where the people or affected wildlife are located, possibly including biomonitoring using biomarkers and genomic markers. The current tools such as EnviroFacts and the TRI, which don’t really tell you anything about what you’re being exposed to aren’t what’s needed for community-based risk assessment. Also, the existing regulatory and legal framework, which is source- and industry-based, becomes an impediment to this very sensible risk-based approach. Who “owns” the liability and responsibility for what pollution? How do you prove that my releases (says the local chemical company) are producing your body burden? That regulatory framework is also going to become an impediment to implementing sustainable chemical production techniques (“green chemistry”), an initiative that also will revolutionize environmental protection.
Without a new paradigm in environmental protection that’s community-based, or oppressive enforcement of the current command and control regulatory framework, we’ll continue to have problems such as kids getting rashes and having their teeth fall from contaminated drinking water.
Enter data judo (to be continued).
This is something that sounds so cool as an exposure monitoring technology that I hope it pans out experimentally and can be deployed.
Lung cancer cells may exude volatile organic compounds different than normal cells, principally as the byproducts of oxidative stress and byproducts of reactive oxygen species (ROS)-induced processes. The differences may be detectable in breath samples. A monitoring tool is being investigated as a non-invasive way to identify non-small-cell lung cancer. The objective for this tool would be to increase the odds of starting treatment while the disease is in its early stages and still localized. The analytical method involves an array of gold nanoparticle sensors in combination with pattern recognition methods; this level of description is what has been found in the press coverage, and having written it I realize I know as much now as I did before hearing about this technique, which is zip. I’m reading the paper trying out the methodology with headspace samples of tumor cell lines, published in the journal Small and realizing I have a lot of catching up to do on analytical methods. . . .
The sensor can discriminate the breath of normal individuals from lung cancer patients, overcoming the problem of high humidity in the breath samples (a problem with the prior method using carbon nanotubules) and without requiring preconcentration of the breath samples (which would require more complex laboratory techniques). Hossam Haick, the lead investigator estimates this method could become available as a diagnostic tool in about three to five years.