A Very Odd Coincidence

UntitledOne of the great pleasures of swanning round giving talks on biology and stuff to anyone who’ll listen is meeting an amazing range of wonderful folk with a seemingly limitless number of interesting and clever questions, asked either at the end of a lecture or, quite often, when they queue up afterwards to raise personal points or chat about their own experiences. Wide-ranging though the topics are, there’s one word I can’t recall coming up even once. No surprise really. It’s a very rare disease, even though it’s a kind of sub-group of the lung cancers that kill more people every year than any other type – over one and a half million world-wide in 2012 when there were 23 new cases in every 100,000 people. In the USA the incidence is 38 per 100,000, in Australia it’s 27. The very rare form is called mesothelioma – that’s the one where there’s almost always a history of exposure to asbestos. Rarely mentioned though it is, mesothelioma came up after a lecture I gave last week in the sumptuous premises of the Union, Universities & Schools Club, just up the road from Circular Quay in Sydney, when a gentleman from the audience revealed that his wife had contracted the disease and described how he was seeking the next round of treatment options for her. He was kind enough to say that he was a follower of my blog but he hadn’t trawled sufficiently far back to track down a piece I wrote about a lady called Heather Von St. James. To my considerable embarrassment, I couldn’t on the spur of the moment recall what I’d called it (What’s it all about?  Serves me right for trying to be clever with titles: the idea of this one was convey Heather’s determination to have a life with her children and husband in spite of being dealt the really rough hand of mesothelioma). What is it all about? In contrast to the overall incidence figures for lung cancer, mesothelioma afflicts just under one white American in every 100,000, so it is indeed pretty unusual. The UK has the highest rate (top of something then!) but Australia comes second with 2.9 new cases of mesothelioma per 100 000. Since the early 1980s over 10,000 Australians have died from the disease and the rate is still rising. It’s predicted to start falling after 2020 but, even so, a further 25,000 Australians are expected to die from it over the next four decades, the majority being men. Now Sydney, as you may recall, is the largest city in Australia and it’s in New South Wales, so you might predict that, if you were going to run into mesothelioma anywhere outside the UK, Sydney would be the spot. But why? Well, NSW was the first state in Australia to mine asbestos and it produced the bulk of the chrysotile (white) and amphibole forms. Asbestos of whatever type is now classed as carcinogenic but it was not until the end of 2003 that the use of all forms of asbestos was banned in Australia. The hazard remains, however, because of the widespread use that had been made of asbestos for construction, both residential and commercial. The risk can be seen from the near doubling of mesothelioma incidence in NSW between 1987 and 2006, with an even bigger increase being seen in women – attributed largely to second-hand exposure. And the freaky happening? The very next day after my conversation at the Universities Club, and completely out of the blue, I received an email from Heather about what she describes as her ‘life’s mission to educate people about this deadly disease’. Having told the story, perhaps the most helpful thing I can do by way of supporting this remarkable lady is to spread the word of her initiative by advertising the web site.

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Powdering Your Nose and Other Parts

If you were asked ‘What is the worst thing about being a research scientist?’ you might well come up with ‘Feeling stupid every day’ – especially if you’d read Martin Schwartz’s wonderfully funny and incisive essay ‘The importance of stupidity in scientific research’ pointing out that research means battling with the unknown. Bad though that is, I can tell you, on the basis of collecting absolutely no data whatsoever, that 100% of scientists would answer ‘Literature’ – or to be slightly more expansive ‘Keeping up with published research.’ To give the rest of mankind a feel for their problem, suppose you work on a gene called MYC which is one of the most powerful cancer drivers: the Web of Knowledge database lists 3,839 hits for MYC as a topic and 468 with it in the title (which means you really ought to read those papers!). So far this year! That’s six months  worth!!

Dusting down the literature

Broadly speaking, scientific literature comes in two categories: a huge one that you might call worthy but dull and a tiny one to which you ought to say ‘Wow!’, that is, there’s some amazing revelation about the way life works, a brilliantly clever method or some stunning insight. But there are two other small classes of which we rarely speak. One is, of course, stuff that is poor (or worse still plagiarized) and should never have been published. The other is perfectly OK – indeed you might even say ‘good someone’s done it’ – it’s just that your heart sinks when you see the title because you know what’s in store.

talc-powder

My latest heart-sinker is a zippy little thing called Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls and it has that effect because the title tells all. They’ve tackled a question that’s been around for 30 years, namely whether applying talcum powder to the nether regions can cause cancer of the ovaries, by pulling together data from separate studies with mixed conclusions, so that a kind of average emerged from the haze as a modest increased risk.’

What’s my problem?

Being certain that such a title will be picked up by the press and reported in a misleading and over-hyped fashion. Step forward the MailOnline (Women who regularly use talcum powder to keep fresh raise their risk of ovarian cancer by almost a quarter SHOCK HORROR!!). OK, I added the last two words but they were there by implication. It has to be admitted that the scientists didn’t help by calculating Odds Ratios (the ratio of the odds of an event occurring in one group to the odds of it occurring in another group), with the inevitable result that they were interpreted as ratios of risks, which overestimates the effect. However, if journalists actually bothered to read the papers they latch on to, it might occur to them that a balanced picture might be conveyed by quoting what the scientists themselves said. In this case the odds ratio was 1.24 which they summarized as ‘Genital powder use was associated with a modest increased risk of epithelial ovarian cancer.’ It would also help the non-scientist reader to put things into context by, in this case, noting that for ovarian cancer the average lifetime risk is about 1.4%. Thus even if you did have an increase of one quarter, the risk is still less than 1.8%.

The ordinary reader might also appreciate a comment on some of the problems faced by such studies. Not the least of these is that they are retrospective (i.e. they asked folk to recall what they used, when and how). It’s not difficult to be skeptical about the precision of the responses, especially when you’re tiptoeing around in what might be called delicate areas, and that’s before you mention the different wording in each study of questions that were pretty convoluted anyway. It’s also worth noting that the analysis showed no increase in risk with prolonged use, which is a little odd (recall that for smoking the more you do it the higher your chances of lung cancer).

Anything else worth adding?

Talcum powder, for this is what we’re talking about, is made from talc which is mostly magnesium, silicon and oxygen and the powder is, of course, widely used because it absorbs moisture and reduces friction, helping to keep skin dry and rash-free. Asbestos, another silicate, occurs together with talc in nature, and it causes the form of lung cancer called mesothelioma. Before 1976, talcum powder was commonly contaminated with asbestos but since the 1970s talcum products have been asbestos-free. There is evidence both in humans and rodents that talc particles can travel up through the genital tract and alight on the surface of the ovaries. Such particles can cause inflammation, one way in which cancer development can be set off, but there is no evidence that talc does promote ovarian cancer in this way.

Ideally in looking for cause and effect, scientists like to get a handle on mechanism. Somewhat surprisingly, for an effect that is modest at most, there is the glimmering of a lead. It comes in the form of a family of enzymes that can detoxify carcinogens (they’re glutathione S-transferases) but the genes encoding two of them, GSTM1 and GSTT1, are missing in about 50% and 20% of Caucasians respectively – so, of course, their activity is lost. There is one study showing that women with GSTM1-present and GSTT1-missing have a stronger association between talc use and ovarian cancer risk. The number of cases is small and it is possible that the effect is not real. It’s also not at all clear how the actions of this combo might interact with the effects of talc. Nevertheless, it is striking that it’s the only pairing of these two genes that shows an association.

What’s a girl to do?

1. Don’t read anything by a journalist that talks about Odds Ratios because the odds are they won’t have a clue what they’re on about.

2. Do read Thou Shalt Not Report Odds Ratios’, Mark Liberman’s witty but brutal evisceration of two ‘science editors’, Mark Henderson of the London Times and Steve Connor of the Independent newspaper.

3. Note that the authors of this study say that genital powder exposure is associated with a ‘small-to-moderate increased risk.’ – nothing stronger than that.

4. Remember that there’s no evidence that talcum powder applied anywhere other than the genital area can cause any problems and that includes the lungs. Even rats forced to inhale talc for 6 hours a day, five days a week for over two years were reluctant to get lung cancer although the incidence did increase in females (maybe they were just trying to escape the Dickensian smog ‘Strewth guvnor, I ’ardly get to see the nippers these days: may as well end it all by getting lung cancer’).

5. Bear in mind that the International Agency for Research on Cancer (IARC) classifies talc-based body powder as a class 2b carcinogen “possibly carcinogenic to human beings.”

6. Be aware that the major factors increasing the risk of ovarian cancer are (1) increasing age, (2) family history of breast or ovarian cancer, (3) being overweight and (4) hormone replacement therapy, whilst having children and breastfeeding them as well as taking the pill reduce the risk.

7. Finally, if the possibility of a slight increase in a small risk really spooks you, avoid orifice powdering and let nature take care of things. Or, if you’re really desperate for friction-free movement, use cornstarch powder: it’s a carbohydrate and there’s absolutely no evidence that it is a risk factor for ovarian cancer.

References

Terry, K.L., Karageorgi, S., Shvetsov, Y.B. et al. (2013). Genital powder use and risk of ovarian cancer: a pooled analysis of 8,525 cases and 9,859 controls. Cancer Prevention Research Published OnlineFirst June 12, 2013.

http://www.dailymail.co.uk/health/article-2343974/Women-regularly-use-talcum-powder-increase-risk-ovarian-cancer-24.html

Gates, M.A., Tworoger, S.S., Terry, K.L. et al. (2008). Talc use, variants of the GSTM1, GSTT1, and NAT2 genes, and risk of epithelial ovarian cancer. Cancer Epidemiology Biomarkers & Prevention 17, 2436-2444.

http://itre.cis.upenn.edu/~myl/languagelog/archives/004767.html

What’s it all about?

The main aim of this blog is to stimulate and hold your interest in cell and molecular biology and especially to try to keep you up to date with exciting cancer developments in a kind of follow-up to Betrayed by Nature. Which I hope is great but, in focusing on the wonderful science, there is a tendency to overlook the fact that it’s really all about people – of which there are two groups: those who find this whole field of science fascinating, whether they actually work on cancer or not, and those who have to deal with it in themselves or in their friends and loved ones. And of course the two come together sometimes, as shown in the dramatic story of Dr. Lukas Wartman, told in Genetic Roulette in a New World.

Even before BbN was published it had changed my life in the most wonderful and unexpected of ways through people who had contacted me to tell of their adventures in coming to terms with the Big C and who were also kind enough to say very nice things about my book. Most recently they have been joined by Cameron Von St. James and his wife Heather who have produced a short video about her cancer experience (http://can.cr/heather). It’s beautifully made, it’s stimulating, informative, moving and amusing. Above all it is inspiring for all of us who have anything to do with cancer – and that really does mean all of us.