Archive for the ‘Genomics’ Category
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