Nutrigenomics in the News

In a way, it’s kind of cool that genetic testing is now available at the drugstore. The New York Times today carries a story about Sorenson Genomics which has started selling a paternity test kit through Rite Aid stores in California, Oregon and Washington. Left unexplored in the Times story was the backstory about why uncertain paternity might be a significant problem to the point of being a market segment for a test kit (if that’s too oblique, it’s the question about who’s banging who). But what’s of interest to me is the spread of genetic testing directly to consumers. Genetic tests, for health and diet advice, ancestry and paternity, are already available directly to consumers through the Internet.

Nutrigenomics holds the promise of being able to identify how genetic variability and diet might combine to create health disparities in human populations. According to the National Center for Minority Health and Health Disparities (NCMHD) Center for Excellence in Nutritional Genomics, the goal of nutrogenomics is to. . .

. . . reduce and ultimately eliminate racial and ethnic health disparities resulting from environment x gene interactions, particularly those involving dietary, economic, and cultural factors. Our goal is to devise genome-based nutritional interventions to prevent, delay, and treat diseases such asthma, obesity, Type 2 diabetes, cardiovascular disease, and prostate cancer.

In addition, there is an evolution in the field of toxicogenomics, which attempts to understand health effects associated with the interaction of genes and environmental toxicants. Advances in toxicogenomics have been spawned by the results from the Human Genome Project, which has characterized in detail the composition of DNA in human cells. Toxicogenomic methods have allowed researchers to begin studying toxicant-induced genomic expression, with applications such as screening chemicals for hazard identification, monitoring toxicant exposure, assessing mechanisms of toxicity, and predicting individual variability to exposure to toxicants.

Toxicogenomics holds the promise of enhancing our ability to estimate the risks from chemicals in the environment. While the value of toxicogenomics in assessing health risks is widely recognized, there are limitations to the methods and data currently available, and further work is needed to fully understand and apply the results from toxicogenomic studies. As yet, there is no coherent regulatory framework for managing environmental health hazards with toxicogenomic methods. Finally, there are social implications to be considered from toxicogenomic applications. For example, there are legal and ethical consequences associated with the ability to specifically identify individuals who may be genetically susceptible to exposure to specific toxic substances.

The National Research Council (NRC) has recently published a report examining the potential impacts of toxicogenomics on predictive toxicology. This report was prepared at the request of the National Institute of Environmental Health Sciences (NIEHS). The report recommends that regulatory agencies enhance their efforts to incorporate toxicogenomic data into risk assessments. However, these data currently are not adequate to replace the current testing programs used in regulatory toxicology. The report makes recommendations for improving the capabilities of toxicogenomics in the areas of exposure assessment, hazard screening of chemicals, and evaluation of population variability and individual susceptibility. Toxicogenomics also has the promise of improving dose-response assessment by providing insights on mechanisms of action, improving the confidence in cross-species extrapolation, and improving understanding of effects with low-dose exposures, particularly developmental effects that might occur with early-life exposures.

Which brings us back to over-the-counter genetic testing. The Times story draws attention to Myriad Genetics which markets a test for the presence of mutations in the BRAC gene which is an indicator of susceptibility to breast cancer. Apparently the BRAC1 and 2 genes are intellectual property of Myriad’s, a development that has some people salivating at the financial opportunities and at the same time, made me rapidly aware of how little I know about this expanding market segment. Last year, the National Academy of Sciences published a study, at the request of the National Institutes of Health, on the granting and licensing of intellectual property rights on discoveries relating to genetics and proteomics and the effects of these practices on research and innovation.

According to the Times, Myriad engendered some controversy over releasing a breast cancer test kit, though it doesn’t go into any of the details (while that’s a topic for another day, a little of the story is here).

Congress asked the Government Accountability Office (GAO) to investigate Internet companies which offer health or nutritional counseling based on genetic testing. The GAO’s results, true to form, identified the potential for fraud and abuse, with testing companies recommending expensive nutritional supplements to address so-called genetically-related health problems. Legislation may be forthcoming. I’m in faint agreement with the author of the American Spectator article about the usefulness of additional regulation. What we need instead are better-educated consumers.

What’s New with TCE?

Not a lot, it seems. TCE has been in the center of a regulatory tangle going back over seven years, which has delayed the development of health criteria based on the most current health effects data. Over 15 years ago, EPA withdrew the cancer slope factors used to assess human cancer risks from TCE, because it was questioned that those values, derived from studies in rats and mice, adequately reflected the cancer hazard in humans. About seven years ago, the EPA began reassessing the science associated with the health risks of TCE, and issued in 2001 a draft report of that reassessment. That report concluded that evidence for TCE being a human carcinogen was stronger than previously believed, and that TCE was a more potent carcinogen than previously believed. After a contentious public review period with the science in EPA’s draft reassessment being closely questioned, the National Academy of Sciences took up a review of the EPA reassessment in 2004. Over a year ago, the National Academy of Sciences published its findings, validating some of EPA’s conclusions, and sending others back for further study; for example, EPA’s conclusion that TCE was a more potent carcinogen was judged by the NAS to be based on weak evidence.

EPA’s TCE web page doesn’t provide a schedule for when its risk assessment is going to be updated. There doesn’t appear to have been a lot of new data generated in the past year, based on what’s available in PubMed. One meta-analysis of occupational epidemiology of TCE exposure and liver cancer attempts to rebut the finding from the NAS study that high-dose TCE exposure, such as found in some workplaces, may be relevant to human cancer risk. This is relevant with regard to liabilities for past exposures (and is probably the origin for the study), but may eventually become a moot point. TCE releases are decreasing with time according to the TRI, which suggests that between pollution prevention initiatives and lingering concerns about groundwater contamination and exposure liabilities, businesses using metal cleaners or solvents are finding alternatives for TCE.

Another study investigated the association between TCE exposure and mutations in the von Hippel-Lindau (VHL) gene, which has been identified as a mechanism for kidney cancer. They examined several kidney cancer patients who may have had high TCE exposures in the past but didn’t observe a relationship between VHL mutations and TCE exposure. This doesn’t necessarily mean that TCE isn’t a kidney carcinogen in humans (the NAS concluded it’s likely there’s a relationship between TCE exposure and kidney cancer), but that further investigation may be needed to understand the mode of action for kidney cancer.

EPA scientists published a paper earlier this year discussing the difficulties in understanding the mode of action for TCE (in this case, with regard to liver cancer), which I suppose explains in part why a finalized risk assessment isn’t available yet. Congress is getting into the act with TCE, a development that absolutely floored me when I first heard about it back in August of this year. Senate Bill 1911 (S.1911), sponsored by Sen. Hillary Clinton and with bi-partisan support, would “amend the Safe Drinking Water Act to protect the health of susceptible populations, including pregnant women, infants, and children, by requiring a health advisory, drinking water standard, and reference concentration for trichloroethylene vapor intrusion (note: someone should remind Congress that the RfC doesn’t address cancer effects), and for other purposes”. It’s currently in the Senate Environment and Public Work Committee. Nothing has happened yet, but it’s still surprising that Congress is getting involved. Three years ago, I asked the question:

What’s next if the NAS can’t provide some good recommendations? Take it to Congress? I can’t wait to see that: “quick, we need to put aside the war on terror so we can debate this drinking water standard for TCE”.

This is one case where I hate being right.

The Tangled Story of Bisphenol-a – A Preview

So we’re all carrying around small traces of the chemical bisphenol-a (BPA), used to make polycarbonate food and drink containers, epoxy coating for canned foods and sealants in dentistry.

And, according to the Chapel Hill consensus published in August 2007 in Reproductive Toxicology (Volume 24, Issue 2 behind a firewall, but I found a draft copy here), these levels of exposure are within the range at which very subtle, adverse health effects have been observed in laboratory animals. As yet, the occurrence of similar effects in humans hasn’t been attributed to bisphenol-a exposure; then again, it’s very challenging to link specific health effects observed in human populations to specific environmental exposures (for example, where do you find an unexposed control population).

Many conservative and libertarian types prefer that government keep out of the business of regulating chemicals in the environment, particularly those chemicals associated with commercially successful products. Their preference is to let the market squeeze out the problem chemicals – if those products are objectionable or harmful, then people won’t purchase them, and those products with the offending chemicals will disappear from the marketplace and won’t be a source of exposure.

However, markets work imperfectly when information is imperfect. There’s potentially a long latency period between exposure and the occurrence of health effects (breast and prostate cancer; adverse behavioral effects) with bisphenol-a. These effects in human populations are not unique to bisphenol-a, and might be attributable to other causes and sources of exposure. Without being able to draw a convincing exposure-effect relationship, the costs of treating cancer cases, or educating behaviorally-impaired kids or adults, which might have been related to bisphenol-a exposure cannot be incorporated into the price of plastic products made from this substance. It is difficult to inform consumers about the risks associated with bisphenol-a; the scientific issues surrounding the health effects are complex, fraught with significant uncertainty and a little scary, particularly if you’re a women of childbearing age. The economic footprint of polycarbonates and epoxy coatings is large, meaning those affected industries have the resources to shape the public debate around this substance.

This wasn’t the bisphenol-a post I wanted to write, but I’m still bogged down trying to connect the dots on this chemical, and the story is taking longer to pull together than I’ve expected. The story has become extremely tangled and hard to follow, with both scientific and political elements to it. See for yourself, at the National Toxicology Program’s Center for the Evaluation of Risks to Human Reproduction (CERHR) web site. While it is important to remain open to the possibility exists that leaching doesn’t produce significant health effects, making a decision that the risks from bisphenol-a are insignificant (i.e. take no further steps to regulate polycarbonates and epoxy resins contacting foods) with the current state of knowledge would be more of an act of faith rather than reason. In addition, it is sadly apparent that the mainstream media in its current form is not up to the task of informing people adequately about this issue. A good story, which I’ve discussed previously, can be found at PLOS. However as I’ve dug into this issue, I’ve found that that story only scratches the surface of this issue. Still it’s a better start than you’ll find in the mainstream media.

There are alternatives to polycarbonate sports bottles and childrens’ sippy cups. For those of you who don’t wish to wait for the scientific assessment to grind to completion, a precautionary approach in the face of the uncertainties about the health outcomes could be to turn to those alternatives. The alternatives to canned foods might be a bit more difficult, but there are some resources available online to find those alternatives (I’m compiling that information too for later posting, but feel free to Google “bisphenol-a free” if you want to read ahead).