The Costs of Cancer Treatment

Something to think about from a Slate book review, via Thus Spake Zuska:

Provenge has shown some success against advanced prostate cancer. But it also costs about $93,000. Gleevec can cost $4,500 per month. Revlimid, another cutting-edge treatment for multiple myeloma, can cost $10,000 per month. It's hard to see how these prices might come down when the market consists of patients increasingly fragmented not only by type of cancer but even by types of mutation.

Or course this isn't a call for 'silver bullet' treatments; cancer isn't just one disease. But the economics can be tricky. Simple supply and demand suggests that market fragmentation and personalized medicine will only drive prices up and split research dollars. It isn't quite so simple, though. Most personalized medicines will be built on common technologies which could even have the opposite effect - higher demand for core technology, modified on a case-by-case basis. Still, looking at the above costs of cancer treatment, I'm glad to live in a country with universal health care.

What Should You Know About Cancer?

A recent paper published in Patient Education and Counseling tries to answer the question: What should a layperson know to be considered "cancer literate"? To do so, the authors assembled a panel of cancer experts (oncologists, GPs, nurses from oncology wards, social workers, public health experts) who refined the answer over a number of rounds. For their purposes, literacy was "the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions." Below is the table of their decisions (click to enlarge)

There are some key areas that are focused on: Aspects of cancer risk, aspects of information/detection, treatments, and coping with cancer/support. Some exclusions make sense, such as how tumours develop or rules for financing screenings, which are secondary to the average person being able to make appropriate health choices. Others are a bit more confusing. For example, knowing about behaviour or environmental factors that contribute to cancer are included in the concept of cancer literacy, but not knowledge about hereditary factors. Likewise, knowing about screening tests and their benefits is included, but not knowledge about groups for whom screening is advised. Cancer symptoms and warning signs also doesn't make the list, nor did limitations of screening, diagnostic procedures, or treatments

What do you think? Keeping in mind the goal is that a cancer literate person be able to recognize the need to consult an expert, but not to become an expert themselves, what should a person know to be considered "cancer literate"?

RIP Cedric

You may remember stories here and elsewhere about transmissible cancer among tasmanian devils. Devil facial tumour disease (DFTD), as it's called, isn't spread by a virus but rather by allografts of tumour cells of Schwann cell origin that spread from animal to animal by biting. This had raised some interesting questions about the immunology of these tumours. How do they avoid immune rejection? Is it possible to create a preventative vaccine?

One key thought to hold the answer to DFTD that has wreaked havoc on the tasmanian devil community is Cedric, a devil that was thought to be immune to the cancer. But alas, Cedric was recently euthanized after two facial tumours that had been surgically removed had been shown to have spread to the animal's lungs:

In 2007, Menzies researchers injected Cedric and his half brother Clinky with facial cancer cells. Clinky developed the disease, but Cedric showed an immune response and grew no tumors — giving researchers hope that he could help them create a vaccine.

But in late 2008, Cedric developed two small facial tumors after being injected with a different strain of the cancer, which causes grotesque facial growths that eventually grow so large, it becomes impossible for the devils to eat. Current estimates suggest the species could be extinct within 25 years due to the prolific spread of the cancer.

Researchers removed the tumors, and Cedric appeared to be rallying. But X-rays taken two weeks ago showed the cancer had spread to the 5-year-old's lungs, Kreiss said. Tests confirmed the lung tumors were a result of facial tumor disease.

This is a blow to the scientists trying to understand and curtail the spread of DFTD, but hopefully data from Cedric will push forward new strategies to help the devil population.

Fructose induces nucleic acid synthesis in pancreatic cancer cells

A quick read of an article summarized in the mainstream media suggests that at least some cancer cells metabolize glucose and fructose differently. This defies the conventional wisdom that, metabolically speaking, these sugars are interchangeable. While fructose fed cancer cells do not have increased proliferation, the study suggests fructose is used more readily for nucleic acid synthesis. Glucose in the same cells is used primarily for energy resulting in lactate and CO2 production. Additionally another recent article demonstrates that breast cancer cells exhibit a more aggressive phenotype when using fructose as a carbon source. As the Reuters article suggests, this may be of public health significance as consumption of free fructose has increased 10 fold between 1970 and 1990.

DCA Patient Trials

You may remember a few years ago, there was buzz out of the University of Alberta about a simple molecule, dichloroacetate (DCA), that was effective at inhibiting aerobic glycolysis and slowing the growth of cancer cells in vitro and in mouse models. This was hailed in some quarters as a miracle cure, others claimed it would never see the light of day because Big Pharma would keep it down, unscrupulous peddlers seized a money-making opportunity and more sensible people took the data for what it was and awaited further investigation and proper trials.

The first patient trials have now been done, and the results are in. Surgically excised glioblastomas showed signs of reversal of the Warburg effect and increased apoptosis.

The clinical trial was quite small, involving 5 patients with neuroblastoma being treated with various standard therapies plus DCA. Three showed regression of their cancers, though it's not certain whether it was the DCA or the existing treatment responsible for the change.

Both Abel Pharmboy [Dichloroacetate not yet an effective treatment for aggressive brain cancer] and Orac [Dichloroacetate (DCA) and cancer: Déjà vu all over again] have excellent descriptions of DCA, how it works and analysis of the trial on their respective blogs. The bottom line seems to be that DCA remains interesting, but needs to benefit from more research and well-designed trials before moving to a real treatment.

Smoking Rolling and Cancer

Another recent stimulating conversation raised the following question: Do people whose livelihoods depend on hand rolling cigars have higher rates of cancer in their fingers or hands? Or, in other words, does handling tobacco affect your risk of certain cancers?

Unfortunately, there isn't much information out there on the subject. But here at the Bayblab we don't take "I don't know" for an answer, so rather than disappoint our reader here's what the literature has to say:

First off, most of the relevant research out there deals with cigarettes not cigars, but they seem a reasonable proxy to answer the original question. Secondly, there is very little dealing with rolling and not smoking.

Some background on roll-your-own (RYO) cigarettes - Compared to factory made cigarettes, smokers of RYO are exposed to similar carcinogen levels as measured by post-smoke metabolic markers. This is true both unadjusted and adjusted for variable such as puff duration, BMI and age. However in Canada, where 17% of smokers use RYO cigarettes, those smokers are less likely to quit, more addicted to nicotine and heavier smokers.

Smoking is known to have cutaneous effects such as poor wound healing, premature skin aging and of course oral cancers. Association with melanoma is inconclusive. However, in studies of melanomas on the palms and soles, there is actually in inverse correlation with smoking.

Again, this all has to do with smoking an not rolling. Presumably smokers have more skin contact with tobacco and tobacco smoke than non-smokers - think of the telltale yellow fingertips - yet have reduced incidence of melanomas in this area. This suggests that dermal contact with tobacco, while contributing to several other conditions, doesn't increase the risk of cancer in the finger or hand. Taking this, and despite the dearth of data on rolling alone, I will tentatively say that the people hand rolling your cigars on your next trip to Cuba are not at considerable increased risk of 'finger cancer'. But I will await the definitive study.


To read more about cancer and cancer research, check out the latest edition of the Cancer Research Blog Carnival that went up at Health and Life on Friday.

Dental Cancer

An interesting conversation on the weekend somehow made its way to teeth and whether there were particular kinds of oral cancer specific to the tooth. Maybe our dentist readers can fill in some knowledge gaps here.

Tooth enamel has no living cells and so, unlike bone, cannot repair itself or become cancerous. However, the tooth does have living cells in the dental pulp, so perhaps they may be susceptible to transformation and uncontrolled growth. Clearly the easy answer would be to consult Pubmed. An even easier solution is finding the one paper that already did that for you, in this case a paper in The Lancet Oncology entitled Teeth: malignant neoplasms in the dental pulp? From the abstract:

[U]sing the search phrase “dental pulp” combined with “sarcoma”, “carcinoma”, or “neoplasms” in PubMed when using the MeSH search mode yielded no reports on primary malignant neoplasms. However, a hand search yields clinical reports on pulpal tumours that were published over a century ago.

OK, so tooth tumours do happen - or did over a century ago. Why aren't there any today? Water fluoridation? The authors offer some thoughts about that:

Because of the restricted space in a tooth, tumour expansion will probably lead to the formation of irritation dentine by secondary odontoblasts and, subsequently, to a haemorrhage infarct of the pulp. One hypothesis states that a purported neoplasm of the dental pulp leads to a chronic appositive pulpitis and–sooner or later–will be treated likewise by root-canal treatment or extraction.

So dental cancers may be happening with some frequency but manifesting and being treated as other conditions. Or maybe the dentists really know what's going on and would rather pocket the treatment fees themselves rather than referring patients for radiation and chemo. They are, after all, in the pocket of Big Floss.

Cancer Vaccine Clinical Trials

A clinical trial for a new treatment for ovarian cancer and melanoma is about to begin using a vaccine developed at Cornell University. From the press release:

The melanoma trial is being conducted at New York University Medical Center, while the ovarian cancer vaccine trial is at the Roswell Park Cancer Institute in Buffalo, N.Y. The trials are assessing the safety and the anti-tumor immune response of the so-called NY-ESO-1 recombinant protein cancer vaccine alone and in combination with other agents, according to the Cancer Research Institute (CRI), an organization that has recently given $450,000 to Cornell to support vaccine production at the Bioproduction Facility. The facility is a partnership between the Ludwig Institute for Cancer Research and Cornell.
The goal of these trials is to maximize the body's immune response to the NY-ESO-1 protein.

NY-ESO-1 is an antigen found in normal testis and in various tumours. The peptide vaccine stimulates the immune system against cells expressing the NY-ESO-1 antigen leading to lysis of tumour cells (no word on how it affects 'normal testis'). The vaccine isn't meant to be preventative, but rather to stimulate the body's response against an existing tumour.

Bayblab Foundation Offers One Billion Dollars for The Cure for Cancer !!!!!!

Attention brilliant young minds of biomedical research, your time has finally come! The BigPharma conspiratists have been permitted to suppress the OneTrueCure for Cancer for long enough. The Bayblab Foundation has decided to finally end the fiasco once and for all. We will be awarding one BILLION CAD to the one to identifty the **ultimate** target for cancer therapy. No magic bullet required (we'll handle that), all you have to do is name the enemy. Should we go straight into the belly of the beast to strike at the tumor cells themselves? They are clearly the agressors, but these genetically labile shape-shifters might be hard to pin down... Should we go after the infrastructure, the tumor's endothelial cells that feed the tumor, or the friendly neighbourhood unknowing accomplices, the stromal fibroblasts? How about the smoke-grenading monocytes laying down the thick cover, or the extracellular matrix protein framework? Or perhaps we shouldn't be destroying bad cells, but strengthening the good guys. Cytotoxic T cells? Natural killers? Antibody-secreting B cells?

What say you Bayblabbers? What do you reason is the best target for cancer therapy and why? Add your answer to the comments below and leave the rest to us...

Systems Tumor Immunology: It's Big Blue Beats Kasparov All Over Again

One innovative approach to cancer therapy involves isolating immune cells (tumor-infiltrating lymphocytes or TILs) from a tumor, and then trying to expand and activate them against tumor antigens in the lab. It can work, but in practice, not an efficient practice. TILs are a mixed bag of cells with all sorts of different personalities, some of which may or may or not be interested in attacking tumor cells. Some, recruited by the ever-devious tumor cells, can even work to supress the activity of the good guys. So sometimes you get a bunch of TILs that work, sometimes not.

A new paper describes a systems biology approach to tackling the complexity of TIL populations with the aim of predicting anti-tumor activity. They profiled the reactivity of a ton of TIL populations, and correlated this inforamtion with a battery of surface markers. They fed the info into some sort of machine learning algorithim, which came up with some pretty clear-cut boolean style predictive rules that a mere organic being (aka tumor immunologist) could never have possibly concieved of with a million years of deductive reasoning and experimental testing.

Check it out:
Rule 1) If the CD8⁺CD28^-CD152^- subpopulation constitutes less than 43% of the entire TIL population AND the CD94+constitutes less than 0.4% of the entire TIL population, then the TIL population is tumor-reactive.

Also, by manipulating the relative proportions of different TIL subpopulations, they could affect reactivity as predicted by their adding machine.

Wicked. Who knew an abacus could do immunology?

See: Predicting and controlling the reactivity of immune cell populations against cancer

Investors keen on cancer vaccine

Reuters is reporting that several brokerages have upgraded the stock of a Seattle company, Dendreon, from 'hold' to 'buy'. The reason? Dendreon is the creator of Provenge, a prostate cancer vaccine expected to get FDA approval sometime late this year.

The reason for the excitement is recent data (presented at the American Urological Association annual meeting) showing a modest improvement in prostate cancer survival rates - a 4.1 month increase, with a 3-year survival rate of 42% compared to 23% for the control group. Oddly, the drug extends survival without shrinking tumours. However, Forbes reports that there is some concern over study design:

Much of the skepticism about Provenge until now has related to the perceived limitations of the 500-person study that Kantoff helped run. It was too small, some experts thought, and had an unusual design in which patients who did not receive Provenge and saw their cancer get worse would receive a frozen-then-thawed version of the vaccine.

This is unusual and may be unprecedented, says Donald Berry, head of biostatistics at the M.D. Anderson Cancer Center. It is possible that this frozen-then-thawed vaccine is actually different from Provenge; if it somehow harmed patients (there's no proof it does), it would actually make Provenge appear more effective. He asks how patients did after their cancer had progressed.

What's cool, though, is that if it works and is approved it will be the first cancer vaccine. The treatment itself is manufactured in part from a person's own antigen presenting cells (APCs, in this case dendritic cells). Patient APCs are extracted and co-cultured with a recombinant fusion protein. The now antigen-loaded APCs are then reinfused where they potentially activate a T-cell response against prostate cancer cells. The full course consists of 3 treatments over 4 weeks with only mild side effects compared to standard chemo treatments.

While the survival increase is quite small, it's encouraging and at least highlights the possibility of this kind of therapy. It would be interesting to know the duration of the immune response. Could this method be used as a preventative measure? How effective would it be against other cancers? (using a different antigen, of course)

mRNA structures translationally prefered by cancer

Translation initiation is often over-activated in cancer cells, however, this over-activation does not favour mRNAs equally. In fact it seems translation over-activation favours mRNAs that promote tumourgenesis and tumour progression. Santhanam et al. in PLoS ONE recently took a look at what general mRNA structural characteristics determine translational activity in cancer cells with over-activated translation initiation. Previously lots of focus has been on the influence of secondary structure and length of the 5'UTR as this has been demonstrated to influence 'translatability'. With new information about microRNAs binding to the 3'UTR to influence translation, an unbiased approach to evaluate their relative influence seems like a very good idea. The methods in this work essentially involved comparing microarray analysis of cell lines with over-activated translation initiation and those without. In each cell line the translational activity of each message was determined by quantification of the percentage of the message that was being actively translated. Then they looked for commonalities in the sequence of the mRNAs that are specifically translationally activated by translational over-activation. (probably using computers) :) Massive data set and unbiased approach = pretty convincing coorelations (we're talking p values of 10E-6)

Here is what cancer cells look for in a potentially translatable mRNA:
1. GC rich 3'UTR
2. secondary structure involving sequences JUST before the start codon and JUST after the stop codon. These results are more striking for the 3'UTR.
3. Short 3'UTRs
4. No microRNA target sites. Indeed the presence of predicted microRNA target sites was negatively coorelated with translational over-activation. (with some exceptions)

The take home message is, somewhat surprising, that the 5'UTR is less correlated with effects on translation over-activation relevant to cancer than the 3'UTR.

Anti-cancer supplement interferes with cancer drug

Herbal supplements are increasingly popular as both prevenative and potentially curative alternative medicine. Often, they're taking alongside standard medication with the underlying assumption that there's no real downside: At best, they'll help; at worst they do nothing. We now know this isn't necessarily the case. For example, St. John's Wort, echinacea and even grapefruit are known to change the bioavailability of certain drugs by acting on cytochrome P450s.

One of the most popular supplements is green tea - consumed either as tea or in more concentrated supplement forms - whose most active polyphenol, EGCG, has been shown to have anti-cancer effects. That being the case, it's no surprise that many cancer patients complement their treatment by consuming green tea.

This may not be a good idea, depending on the chemo drugs being used.

A recent paper in the journal Blood (subscription required, press release here) demonstrates that green tea supplements can interfere with at least one particular chemotherapeutic.

The drug in question is bortezomib (aka Velcade), a proteasome inhibitor that induces ER stress leading to cell death and approved for treatment of multiple myeloma and mantle cell lymphoma. One of the pro-survival regulators in the ER stress response is GRP78. EGCG is known to inhibit GRP78 activity which may be the reason it can senstitize cells to other chemo agents. To the surprise of the researchers involved, the opposite was seen with bortezomib, and the drug's anti-tumor activity was almost completely negated. This was shown both in vitro and in vivo with different cancer models - multiple myeloma and glioblastoma. More importantly, the inactivation of the drug was found to occur with physiologically relevant concentrations of EGCG:

The study findings may have several important implications in the clinical setting. The EGCG blocked bortezomib’s antitumor effects at levels that are commonly achieved with the use of available concentrated green tea supplements (as low as 2.5 μM – which can be attained with two to three 250 mg capsules of green tea extract) suggesting the impact is very real for patients supplementing their therapy. The team also believes that as the EGCG inactivates bortezomib’s function in the tumor cell, it may also prevent some of the side effects that usually accompany the therapy. As a result, patients taking green tea products to supplement their therapy may experience improved well being and feel encouraged to increase their intake while unknowingly blunting or completely negating the efficacy of their bortezomib treatment.

EGCG was found to block bortezomib's proteasome inhibitory activity by directly interacting with the boronic acid group of the drug, forming a new adduct. Vitamin C has a similar, but much less potent, effect.

Of course, this is one very specific interaction and the authors note that it shouldn't minimize any previous beneficial effects reported for green tea. At the same time, it's an example of how complementary medicine doesn't get a free pass for being 'natural'.

Coffee and cancer

I recently had an armchair expert tell me that french press style coffee vs a filtered coffee preparation method increases your risk of cancer. [Don't confuse french press coffee for the biological apparatus]. This person was foggy on the details but indeed got rid of their Bodum(tm). Personally I find coffee from a french press tastes superior, but then again, I'd drink it off a dog some mornings. Some googling revealled one source of the idea that unfiltered coffee increases your risk of cancer the source they cite is an article that shows increased homocysteine levels in drinkers of unfiltered coffee vs NO COFFEE. (no coffee?!?!) Homocysteine itself is not directly derived from your diet, however, high levels in the blood are indicators for high risk of heart attack and stroke, and possibly cancer. The thought was that filtering coffee removed what the authors assumed was causing the rise in homocysteine levels. Turns out filtering coffee doesn't change the fact that drinking coffee raises homocysteine levels.
To me this is a good example of something I see often, that is, cancer research NOT serving the public who funds it. If this is the crappy way that the public is informed about cancer research I'm surprised it still is funded. Someone gets rid of their french press because their concerns for their health based on the mainstream medias reporting of an incorrect assumption in the literature. What is also strange is that the damage is done. I think I would have a hard time convincing this person that their french press coffee is no worse for them.
Also I think there is a leap of logic here that I have heard is similar to the leap in logic made for the statin class of drugs. That is that since higher homocysteine levels correlate with higher risk of cancer (let's assume the one article I found linking the two is correct), then homocysteine is a cause of cancer. An indicator is not necessarily the cause but is merely associated with increased risk.
Also it may be that coffee raises cancer causing homocysteine levels by an appriciable amount, however, other factors associated with coffee drinking may result in an overall reduction in cancer incidence. So again even if homocysteine causes cancer, coffee may not.
Of course, perhaps coffee has so taken over control of my thought processes that I am in denial.

Chili, capsaicin and cancer

Speaking of the infamous journal "Medical Hypotheses", a paper published in 2002 tried to make a link between spicy food and stomach cancer:

"The 'hot' sensation produced by exposure to pepper is apparently due to two natural carcinogens: capsaicin in chili type peppers and safrole in black/white pepper. There are four cookeries in the United States that are noted for their high pepper content: Mexican-American, Cajun, white Creole, and black Creole. Each is largely confined to a single ethnic-cultural group which is concentrated in some counties. By use of county population and mortality data, significantly higher rates for stomach and liver cancer were found in counties inhabited by these four ethnic-cultural groups than in matched control counties."

Could it be true: chilies are carcinogenic? Might as well go to the source to find out, the country where chilies originated: Mexico. A Mexican study looking at associations between gastric cancers, chili consumption and H pylori infection found no independent association between the chilies and the Hp but a weak association with gastric cancer in heavy chili eaters (OR = 1.71; 95% CI = 0.76-3.88, p=0.026).

However there is mounting evidence that chilies may do more good than harm. Spices in general seem to make good candidates according to this recent review:

"the potential of turmeric (curcumin), red chilli (capsaicin), cloves (eugenol), ginger (zerumbone), fennel (anethole), kokum (gambogic acid), fenugreek (diosgenin), and black cumin (thymoquinone) in cancer prevention has been established."

You don't have to look very hard to find that in fact capsaicin has potential to inhibit the proliferation of cells in endometriosis , inhibit the growth of androgen-independent p53 mutated prostate cells, kill melanoma cells etc... The mechanism seem to included apoptosis, autophagy and ROS generation.

All this to say, you can eat your chilies without worrying too much about cancer, the harm done is mostly temporary and the jury is still out for the longer term...

Varmus on "The Cure" for Cancer

“These are incredibly complicated scenes that we're only beginning to understand thanks to the genome project and spinoffs from the genome project.

“And the hope that advocacy groups understandably have – that if we just do a little bit more research and apply it at the bedside, that we're going to cure cancer – is really terribly simplistic.

“And when scientists give support to that simplistic notion, which they are likely to do because it's the way of raising money, they create an expectation that's very hard to meet.”

...And he argued that the culture of unrealistic expectations is encouraged by the way science is taught in schools, with a focus on outcomes rather than process.

(More at the Globe and Mail)

My question: what proportion of research funding currently goes to BASIC cancer biology research with no obvious "therapeutic/therapeutic target" pay-off?

Trans-splicing and Chromosomal Translocations

I'm up for the research group journal club tomorrow. Since a couple of the bayblab readers will not be able to make it, I thought I'd pass on what I'll talk about.
A recent publication in Science, demonstrates that an mRNA in a normal endometrial cells encodes the exact same fusion protein that normally occurs as the result of a translocation found in 50% of endometrial cancers. The transcript, as detected by RT-PCR and RNase protection assay is found in abundances that are affected by hormone treatment and hypoxia, suggesting that it has a biological role. In cancer this fusion protein results in resistance to apoptosis and increased proliferation. However, in theses normal cells, there is no DNA encoding for this hybrid mRNA and the authors suggest it is a result of trans-splicing. Trans-splicing of this sort has not been observed in vertabrate cells and even in other organisms it is quite different.
They go to great pains, of course, to demonstrate that it is not an RT-PCR artifact and that there is not a subpopulation of the normal cells that contain the translocation.
The killer is that they do in vitro trans-splicing assays using Rhesus and Human nuclear extracts and indeed find this chimeric mRNA. I'm sure they are looking for other fusion mRNAs using this assay in a high throughput method.
This study raises some intersting question about these oncogenic fusion proteins that are very common in cancer. Particular fusion proteins are repeatedly found in particular cancers. Do they have a function in normal cells? Is it through the mechanism that produces these mRNAs or the mRNAs themselves that cause these cancer associated translocations??
At least check out the figure. Translocation is indicated in the centre of the figure. Two mRNAs combine to create a novel one that has no DNA equivalent.

Early Cancer Detection: Dogs with frickin' laser beams

You may recall from several years ago, reports of dogs who could sniff out cancer. Based on odour, trained dogs could distinguish urine from bladder cancer patients from controls at a better-than-chance rate (mean success rate of 41% vs. 14% expected by chance alone in this study).

Since then, more canine cancer detection experiments have been done. In 2006, this double-blind study showed that ordinary household dogs could be trained to identify breast- and lung-cancer patients with incredible accuracy (88% and 99% respectively) and specificity (98% and 99% respectively) compared to conventional diagnosis and biopsy confirmation, based on breath scent. The dogs were able to 'diagnose' both early- and late-stage cancers.

Fast forward to 2008. While a Korean company is cloning cancer-sniffing dogs, a group at the University of Oklahoma - intrigued by the dogs, and having already published proof of concept to identify volatile compounds in breath - announced a project to develop a tool for laser-based detection of cancer biomarkers. The goal is to eventually develop an 'electronic nose' for rapid, accurate, non-invasive cancer diagnosis.

According to McCann, “Improved methods to detect molecules have been demonstrated, and more people need to be using these methods to detect molecules given off from cancer. We have developed laser-based methods to detect molecules. Mid-infrared lasers can measure suspected cancer biomarkers—ethane, formaldehyde and acetaldehyde.” McCann will use nanotechnology to improve laser performance and shrink laser systems, which would allow battery-powered operation of a handheld sensor device.

Because of the importance of early detection, this device - if sensitive enough to detect early-stage cancers with a simple breath test - could have major implications for survival rates. Unfortunately right now it's just a press release and, as pointed out in the release, an actual product is 5-10 years away, but in the meantime more biomarkers can be investigated and more cancers can be screened as candidates for laser-based diagnosis. As McCann states, "the science supports it, and the dogs tell us there is something there."

Dial 'C' for Cancer

I'm not a cell phone user. Even my grandfather has made the leap, while I remain in the technological dark ages with a phone attached to the wall with a wire! But despite being completely unreachable the second I walk out the door, there may be a bright side. Last week, the director of the University of Pittsburgh Cancer Institute issued a warning about cell phone use and a potential link to cancer:

The head of a prominent cancer research institute issued an unprecedented warning to his faculty and staff Wednesday: Limit cell phone use because of the possible risk of cancer.
The warning from Dr. Ronald B. Herberman, director of the University of Pittsburgh Cancer Institute, is contrary to numerous studies that don't find a link between cancer and cell phone use, and a public lack of worry by the U.S. Food and Drug Administration.

Now this is something many of us have heard before - cell phones cause cancer - but how true is it? Is this warning warranted, or is Dr. Herberman yelling fire in the proverbial theatre? Since the data this is being based on is unpublished, it's impossible for me to comment on. However, studies on cell phones and cancer have been done, so we can look at the data we have so far.

Several years ago, the US Food and Drug Administration consumer magazine had a piece explaining some of the difficulties in getting an answer to the phone-cancer question. The article included a very brief summary of studies that had been done (as well as some commentary by cancer researchers). The conclusion there was that there is very little to no risk of brain cancer from cell phone use. However, the intervening 8 years has been ample time for further studies to be done. A quick pubmed search shows numerous animal studies that show no increase in cell death or proliferation in mice exposed to non-ionizing radiation of the same frequency used by mobile phones. Many of the human studies (retrospective studies, for example here and here) are also negative, but they aren't exclusively so. While meta-analysis is not ideal for answering this type of question (see here for a brief discussion, particularly Bayman's commentary there), so far this year at least two meta-analyses have been done on the issue. This study found no overall increase of brain tumors (though they note in a subset of the cases included in the analysis that there is a potential elevated risk with long term cell-phone use). Similarly, this analysis is more assertive in its conclusions, claiming "a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period" (while their data show that shorter term use is not associated with increased brain cancers).

So what's the answer? Is there a risk to cell-phone use? The literature seems to indicated that in the short term, no, probably not. Long term (>10 years) usage starts to tilt things towards the positive, although not in a huge way (the studies mentioned above indicate that the increased risk is relatively small). As is usually the case with these situations, the answer will probably bounce back and forth for awhile until a definitive study is done to put the question to rest

This brings us back to the renewed warnings issued last week. Given that the potential risks are small (but not negligible) and associated only with long term exposure, the question becomes what was the proper way to deal with the unpublished data from the University of Pittsburgh Cancer Institute? Again, it's difficult to say without seeing the data in question, but given the information we have so far it's hard to imagine a definitive, home-run conclusion (Herberman, who issued the warning, says as much in the news article). Should he have waited for peer review before sounding the alarm (would an extra few months before releasing it make a difference when talking about a 10 year latency)? Is it better to err on the side of caution? After all, he's not calling for an end to cellphone use, but rather certain precautions, particularly with children. Dr. Herberman defends himself thusly:

Herberman is basing his alarm on early unpublished data. He says it takes too long to get answers from science and he believes people should take action now - especially when it comes to children.
"Really at the heart of my concern is that we shouldn't wait for a definitive study to come out, but err on the side of being safe rather than sorry later," Herberman said.

Without seeing the unreleased data, is it enough to change your cellphone habits? For the University of Pittsburgh statement and the recommended precautions, go here.

Malignancy from organ transplants?

I've always wondered about this: Is it possible to get cancer from a donated organ? In theory the organs are inspected and come from healthy donors, but microscopic lesions would be undetectable. Furthermore, the recipients are on immune suppressants, making the cancer even more likely to develop. In fact it's a common occurrence in recipients to develop de-novo tumours after transplantation, but it's usually from their own tissue and a direct result from the drugs. For example, melanomas are 1.6-2.5 times more likely in the transplant population. Well a story this week explains how a 15y old boy who was mis-diagnosed with meningitis but who in fact had lymphoma, ended up causing the death of 2 of the four recipients of his tainted organs. The other two had the organs removed and are undergoing chemo. I wonder if they have improved chances of survival once they are off the immunosuppressants since the cancers are mismatched or whether the match required for transplantation is close enough for the tumour to behave like a de-novo host tumour... The Lancet has a great review on how to threat both types of malignancies:

"Transmission of an undetected tumour in the donor is rare (incidence 0·02%).⁷⁷ The question of whether a tumour in the recipient has arisen de novo or by transmittance from the donor can be answered by doing a biopsy of the tumour and cross karyotyping the recipient and donor tissue to establish tumour origin. [...] The overall mortality from donor-related malignancies is calculated at 38%, with that of transmitted tumours at 46% and derived de-novo tumours at 33%. Cadaveric-donor-related tumour mortality is 0·007% (8 of 108 062 recipients).⁷⁷"