Archive for the ‘Cancer’ Category
Mehmet Oz is a physician who’s made the most of the opportunities afforded him as a television celebrity. He supports complementary and alternative medicine, which draws in criticism from advocates for evidence-based medicine. Dr. Oz most recently emerged in the news with a “study” highlighting the health risks from arsenic in fruit juices, which given the size of his megaphone engendered nationwide controversy. The FDA took him to task over it, and I picked it up from reading PZ Myer’s blog. PZ does a public service drawing attention to the issue and in particular highlighting FDA’s opinion of Dr. Oz’s data, but didn’t convey anything about the nature of the risks, either significant or insignificant, about arsenic in apple juices. Deborah Blum has a great story about what real arsenic risks look like, depicting arsenism in Bangladesh including a brain-curdling picture of someone with an arsenic-related hyperkeratosis (a disabling thickening and roughening of the skin). She also takes Dr. Oz to task for doing bad risk assessment and bad risk communication. Read the rest of this entry »
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
[Note: this a series of posts stimulated by this recently-published research on breast cancer risks from multiple environmental contaminants. A previous post is here.]
I have been aware of initiatives to address endocrine disrupting chemicals, early-life exposure to environmental contaminants, and cumulative risk assessment but over the past few years hadn’t paid that much attention to them. While all of these topics had public health importance, and were beginning to turn into risk assessment guidance, regulatory agencies just haven’t been requiring them to be used for making decisions about the kinds of problems affecting my clients. So, they were more of an intellectual curiosity.
That might be changing. In 2005, EPA published guidelines for assessing susceptibility from early life exposure to carcinogens. In 2008, EPA updated the screening levels used for evaluating contaminant data at Superfund sites and incorporated the early life exposure guidelines for selected carcinogenic chemicals. Guidance on how to conduct cumulative risk assessments is steadily becoming more specific, and all of this represents a sea-change in how to perform risk assessments which the National Academy of Sciences says is overdue.
A recent review article argues there is substantial evidence that hormonal perturbations early in life (either in utero or during early development) are associated with increased disease susceptibility later in life, with two examples being prostate and breast cancer. The Endocrine Society has recently issued a scientific policy statement (news items here and here; link to the report here) identifying endocrine disruptors as a significant public health concern. The thrust of these stories is that professional societies are becoming involved not in just generating the science but in encouraging that it be used in policy making.
BPA, which was mentioned in the previous post, gets its own chapter in the Endocrine Society’s report. Low-dose exposure in rat fetuses to has resulted in alterations in mammary tissue. Higher dose prenatal exposures (i.e. where the pregnant females are dosed with BPA) increase the numbers of precancerous lesions in next-generation rats later in life. BPA increased mammary tumor incidence in animals when administered along with rodent carcinogens such as nitrosomethylurea and dimethylbenzanthracene. The Endocrine Society’s summary statement is:
These results indicate that perinatal exposure to environmentally relevant doses of BPA results in persistent alterations in mammary gland morphogenesis, development of precancerous lesions, and carcinoma in situ.
Or, exposure to levels of BPA, which you might normally encounter through your daily routine, might, if you’re pregnant, predispose your female child to an increased breast cancer risk. The Endocrine Society speculates that the increased incidence of breast cancer observed over the last 50 years might have been caused in part by exposure of women to endocrine-mimicking chemicals.
Of course, it’s risky to let yourself get tunnel-vision and focus on only one answer. In 2002, reports that post-menopausal hormone therapy posed an increased breast cancer risk resulted in a rapid decline in this kind of hormone use in women. The decline in hormone use is suspected to be a contributor to the subsequent decline in breast cancer rates. Would reducing BPA exposure in a systematic manner, also result in a decline in breast cancer rates? It would be hard to say – an epidemiological investigation of post-menopausal hormone therapy is a good deal simpler than investigating BPA; 93% of Americans have detectable levels of BPA in their bodies – where do you find a control population?
Not done yet. . . .
Bisphenol-a, used to manufacture polycarbonate including plastics for food and beverage containers, has been found to leach from those containers, is consumed by us and can be detected at trace levels in nearly everyone’s blood and urine. Bisphenol-a is hormonally active (otherwise known as an endocrine disruptor), and produces reproductive and developmental abnormalities in laboratory animals including changes in mammary glands. The kinds of changes observed in mammary tissue leads some to be concerned that bisphenol-a might pose some level of risk for breast cancer.
By itself, maybe the breast cancer risk from bisphenol-a (or BPA) by itself isn’t something a woman ordinarily needs to be concerned about. There isn’t any certainty about it, and the effects observed in lab animals are pretty subtle. But we’re not exposed to BPA by itself, but as mixtures of contaminants. Other chemicals that we’re commonly exposed to that are possible human carcinogens are polycyclic aromatic hydrocarbons (PAHs). PAHs are found in tobacco smoke, air pollutants, motor vehicle exhaust, particularly diesel, and some fried or smoked foods. One PAH, dimethylbenzanthracene (DMBA) reliably causes mammary cancer in a selected strain of rat, so that DMBA-rat system is used as an animal model for breast cancer research.
A study published a few months ago in Environmental Health Perspectives explored the hypothesis that exposure to BPA early in life would produce changes in mammary tissue, creating a predisposition for breast cancer. This study investigated the interaction between BPA and breast cancer risks by exposing newborn rats to BPA through lactation, then giving the young female rats oral doses of DMBA.
Those tending to be skeptical about environmental contaminant-disease trend relationships might be inclined to note that breast cancer incidence and mortality rates have declined over the past several years. When you browse the SEER statistics directly (breast, Figure 4.2), mortality hovers a little over 50 per 100,000, while incidence hovers around 300-350 per 100,000. While a decreasing trend is good news, a worthwhile question then is how many cases are too many? Note: yes, I know zero would be nice, but let’s stay in the real world for now. . . . The CDC reports that in 2005, about 186,000 women were diagnosed with breast cancer and 41,000 died from it. Aside from the financial and human costs, there is the issue that a substantial fraction of those cases may still be avoidable.
To be continued. . . .