Tag Archives: cancer

Toms River

TomsRiverToms River is a mystery. Not a mystery about the missing apostrophe, though that does warrant a thorough investigation. Rather, Toms River is a forensic mystery, an intrigue of science and health, of the marvels of chemical manufacturer and of the mischievousness of chemical pollution, and finally of that old conundrum of correlation verse causation. The writing flows like that of a well written novel – good enough that one forgets at times that it is not fiction, but a story about real people and real events. At the nub of the mystery is that so human of all questions, “why?” Why does my son have cancer? The answer provided in Toms River is neither sensational nor simplistic. To try and get near an answer the author must explore the histories of dye manufacture, cancer biology and epidemiology. In that way he provides the skeleton around which the flesh of the events of Toms River throughout the past few decades is built. He does this in a way that is accessible to anyone with a modicum of curiosity. No math needed! Yet the author doesn’t shy away from talking about the difficulties of epidemiology, modelling of water flow, and cell biology.

Some of what you read will shock you, some will enlighten, some will inspire. Five stars.

Christchurch has breast cancer research hub

Guest post by: Kim Thomas, Communications Manager at the University of Otago, Christchurch

Research Radar UOC

A team of specialist cancer researchers have joined forces to focus on the impact of obesity on breast cancer.

The researchers all work at the University of Otago, Christchurch’s Mackenzie Cancer Research Group. The Group is headed by Canterbury District Health Board oncologist Professor Bridget Robinson, a breast cancer expert.

Researchers Associate Professor Gabi Dachs, Dr Margaret Currie and Dr Logan Walker have previously investigated various aspects of cancer but decided to team up and focus on the significant health issue of obesity.

Associate Professor Dachs says that international studies have shown breast cancer patients who were obese before or after diagnosis are less likely to survive than patients with normal BMI. Risk of dying from breast cancer increases by a third for every increment of 5kg/m2 in BMI.

autumn15obesity

From left to right: A/Prof Gabi Dachs, Dr Margaret Currie, Dr Logan Walker

The three researchers are investigating different aspects of obesity and breast cancer:

  • Associate Professor Dachs is looking at molecular factors associated with obesity in cancer, particularly how fat cells communicate with cancer cells and negatively affect them.
  • Dr Margaret Currie is putting fat and breast cancer cells together to see how the fat cells make tumours more resistant to treatment. She suspects the fat cells provide ‘an extra energy hit’ to cancer cells by providing lipids, or fats, in addition to glucose.
  • Geneticist Dr Logan Walker will investigate whether the obesity-related gene responsible for the amylase enzyme in saliva (AMY1) contributes to breast cancer development. He will also explore the role of key genes that behave differently in breast tumours from obese women.

The researchers’ work is funded by the NZ Breast Cancer Foundation, the Cancer Society of New Zealand, the Canterbury and West Coast Division of the Cancer Society NZ, the Mackenzie Charitable Foundation and the University of Otago.

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Prostate cancer and omega 3

The media is in a feeding frenzy with reports of a link between Omega 3 and Prostate Cancer.  Here’s a sample:

Link Between Omega-3 Fatty Acids and Increased Prostate Cancer Risk Confirmed (Science Daily)
Omega-3 supplements ‘could raise prostate cancer risk’ (Telegraph)
Omega-3 supplements linked to prostate cancer (Fox)
Omega 3 could increase cancer risk (TV3)

So, what’s the fuss?  The fuss is about a study published online yesterday in the Journal of the National Cancer Institute:

Brasky, T. M., Darke, A. K., Song, X., Tangen, C. M., Goodman, P. J., Thompson, I. M., et al. (2013). Plasma Phospholipid Fatty Acids and Prostate cancer Risk in the SELECT trial. Journal Of The National Cancer Institute, 1–10. doi:10.1093/jnci/djt174/-/DC1

The article is behind a paywall, so I’m not sure how many of the journalists have bothered to read it instead of relying on press releases.  I’ve access to the paper through my university, so here is a synopsis for the lay reader (bearing in mind I am not an expert in either omega 3 or cancer).

The thinking in the general public: Prostate cancer bad, Omega 3 good, therefore Omega 3 may prevent/delay prostate cancer

The thinking of the scientists: Is there a link between phospholipids (including omega 3) and prostate cancer?

The subjects studied:  Participants were enrolled in a trial of Vitamin E supplementation verse Placebo.  They were all male, from the US, Canada or Peurto Rico, aged 50+ if black (the medical literature uses this description), or 55+ if not, had no history of prostate cancer and with a PSA (prostate-specific antigen) test of <4ng/ml at the start of the study.  They were enrolled between July 2001 and May 2004.  While 35,533 men were enrolled in the trial, in this study only 2273 were studied.  These consisted of 834 patients who had prostate cancer diagnosed prior to 1 January 2008 and 1364 “matched” subjects who had no prostate cancer diagnosed in that time.  This is called a case-controlled study.  The “matching” is a statistical process whereby they make sure the two groups being compared (those with and without cancer) have certain demographic features in common on average.  In this case the groups had similar age ranges and similar ethnicities.  The cancer group was further divided into those with low and those with high grade cancers.

The methods:  Blood samples taken when patients were recruited and the total fatty acid content along with 4 types of Omega-3 fatty acids, 2 types of Omega-6 fatty acids, and 3 types of Trans-fatty acids were measured. The mean (average) proportions of each of the types of fatty acids (compared with total fatty acid) were compared between the No cancer and the Prostate Cancer groups.

The results:  Those with cancer had on average a greater proportion of each of  three of the kinds of Omega-3 fatty acids than those without cancer.  The p values were 0.03, <0.001, 0.006 (see here for an explanation of p values).  The p values for the two Omega-6 were higher (therefore more likely to be arrived at by chance) at 0.17 each.  The Trans-Fatt p values were 0.048, 0.08, 0.002. At this point it is very important to remember that not all those with cancer had high proportions of Omega-3 – it was the average that was higher.  An analysis comparing the 25% of subjects with the lowest Omega-3 (combination of the three Omega-3s) values with those with the highest 25% showed that the risk of prostate cancer was between 9 and 88% greater (with 95% confidence that this was not just by chance), ie a Hazard Ratio of 1.43 (95%CI 1.01 to 1.88).  Considering only those with the highest grade of cancer the Hazard Ratio was 1.71 (95%CI 1.0 to 2.94).

The authors performed a multivariable analysis.  That is when they check to see if other factors may be influencing the results.  They say that for Omega-3:

The continuous multi-variable-adjusted hazard ratios predicting total, …prostate cancer risk, [was] 1.16 (95% CI = 0.98 to 1.36),

This means that Omega-3 proportions changed the risk of getting prostate cancer by between a 2% decrease (100*(1-0.98)) and 36% increase (100*(1.346-1)) when other factors (not stated what) are accounted for.  This is what the 95% CI (Confidence interval) suggests.  The 1.16 is merely somewhere near the middle of the change in risk (16% higher).  It is the confidence interval that matters.  When it crosses 1, as it does here, it is not normally considered very important (ie not “statistically significant” as is often said).

The authors then conducted a meta-analysis for the Relative Risk of getting prostate cancer for two types of Omega-3 (DHA and EPA) and Omega-3 total fatty acid.  A meta-analysis is where they gather up all the studies and combine the results together.  In this case there were 7 studies (including the present one) which reported DHA and EPA and 4 which reported totals.  The results were

EPA:  RR = 1.07 (95%CI 0.95 to 1.21)
DHA: RR=1.16 (95%CI 1.03 to 1.31)
Total: RR=1.14 (95% CI 0.99 to 1.32)

Remember it is the 95% CI that is most important.  In this case only DHA creeps above 1 for the 95% CI.  Remember also that RR (Relative Risk) is a comparison of the rates of cancer between those with the level of Omega-3 among the lowest 20% and among the highest 20%.

The Conclusions:  The authors conclude

…these findings contradict the expectation that high consumption of long-chain ω-3 fatty acids and low consumption of ω-6 fatty acids would reduce the risk of prostate cancer.

This sounds reasonable under the assumption that consuming omega-3 (eg in supplements) actually increases the proportion of omega-3 in the blood.  They also state

It is unclear why high levels of long-chain ω-3 PUFA would increase prostate cancer risk,

What the media said:  TV3 borrowing from Sky, had a graphic with the word “Supplements” prominent and they talked of a 71% increased risk of high grade prostate cancer and 43% increased risk overall.  As we’ve seen these numbers are not what is relevant, the confidence intervals are – this adds a lot more uncertainty to the results (but not such good TV).  Also, they ignored the meta-analysis entirely (numbers not so big or interesting). They said nothing about the age range etc.  Finally, and most importantly, the study was not a study of supplements!  We have no idea why some participants had higher Omega-3 than others.  Some may have been because of supplements, some because of fish eating, some simply because of their own body composition and own metabolism.

My conclusion:  The study did not show that supplementation of Omega-3 is risky.  Nor did it show that supplementation is beneficial. It simply was not a study of supplementation. It did show that elevated proportions of Omega-3 fatty acids are possibly associated with increased risk of prostate cancer in men 50+ (black) and 55+ (non-black). Remember, too, that this is talking about relative risk.  The overall prostate cancer risk during the study period was just 2.35%.  If I’ve done my math right, then those in the top 25% of Omega-3 have an absolute risk of 2.77% (95%CI 2.12% to 3.65%).

 

Do we talk about the right cancers?

We all want a cure for cancer.  This is evident in the ideas put forward for the NZ Science Challenges (http://www.thegreatnzscienceproject.co.nz/home).  Will these ideas reflect the true need in New Zealand? Are all cancers equal or are some more equal than others?  Does the public perception of what is most important reflect the true health risks?  To answer this latter question would require a well controlled survey which I don’t have.  What I can do is look at some data from the media.

First the numbers: The Table below gives the number of newly diagnosed registered and of deaths in New Zealand for various cancers for 2009 (I have only considered those with more than 200 deaths).  The percentages are the percentage of all the cancers listed.  The final column is the ratio of the numbers who died to the number of newly diagnosed.  This is not a proper measure of the likelihood of dying of the disease once it is diagnosed, but probably gives an impression of which are the more and which are the less deadly of the cancers.

Cancer Registrations and Deaths in New Zealand (2009: Ministry of Health, http://www.health.govt.nz/publication/cancer-new-registrations-and-deaths-2009)

Cancer Registrations and Deaths in New Zealand (2009: Ministry of Health, http://www.health.govt.nz/publication/cancer-new-registrations-and-deaths-2009)

The graph plots the percentages for new Diagnoses and deaths against the percentage of stories on the Stuff.co.nz web site for each of the cancers (ie relative to the total number of stories (20,757) for all these cancers.  I’m sorry to pick on Stuff, but it conveniently gave a count with a fast search engine.  The area above the dashed line (blue) suggests under reporting in the media, the area below over reporting.  Brain cancer is vastly over reported on this measure relative to other cancer death rates and new registrations.  Breast cancer is also over reported, particularly in relation to other cancer death rates.  Melanoma reporting reflects its deadliness, but not its new registrations.  Colorectal/Bowel cancer and Lung cancer are relatively poorly discussed compared to their relative death rates.

The percentage of new registrations and of deaths of various cancers against the percentage of stories in Stuff.co.nz.  Note, percentages are relative to the total number of new registrations/deaths/stories

The percentage of new registrations and of deaths of various cancers against the percentage of stories in Stuff.co.nz. Note, percentages are relative to the total number of new registrations/deaths/stories

There may well be many better ways to look at this kind of data – I would appreciate any suggestions.  I hope to look at other diseases as well.  However, as I research a disease that affects as many people as breast cancer each year, is just as deadly, and yet is reported on Stuff 1/50th as often, I am a little biased.

Faith justified? – a vital tale

Expensive pee or elixir of life?  The two extreme views of multivitamins.  I’ve been taking multivitamins for a number of years now.  I’ve taken them on faith backed by a little evidence.  This week, I think for the first time, a randomised controlled trial has provided high quality evidence that my faith is justified.  More on that in a minute.

Most trials of vitamin supplements to date have tested vitamins in isolation.  The trials were justified on the observation that people with certain diseases lacked specific vitamins and/or the scientists’ understanding of biochemical pathways that require the vitamin in question to work well.  This is well and good.  From what I understand most of these trials have failed to show a clinical difference (ie in health outcomes) (see, eg, my report on the Vitamin D trial in Christchurch).

Vitamins (and trace minerals), of course do not exist in us in isolation.  They work together with each other and along with all the other chemicals in us with names that only a biochemist could love.  The theory, which I’ve accepted largely by faith, is that vitamin supplementation works best when it is multiple vitamins together.  Studies of multivitamin supplementation have largely been short term or retrospective observational.  That is, scientists have surveyed people on vitamin use and drawn conclusions based on that.  One such study, the Iowa women’s study(1), caused me to pause and reassess last year when it seemed to indicate supplementation including copper increased mortality in post-menopausal women. Being neither a woman nor post-menopausal I did not panic.

The prospective randomised controlled trial (RCT) is regarded as a much higher level of evidence than retrospective observational studies.  Published this week in the Journal of the American Medical Association (JAMA) is an RCT of multivitamin supplementation in men (2).  Briefly, 14641 men aged 50+ were enrolled in a trial in 1997 and followed until 2011. Participants were randomly chosen to receive either a multivitamin or a placebo.  Neither the participants nor the people running the study knew which people received placebo and which received multivitamin.  This is known as “double-blind.”  Only a statistician knew and he or she did not reveal anything until all the data was in.  The primary outcome was to compare the rates of cancer and cardiovascular disease in both groups.  Secondary outcomes (ie ones that the statistics can not be so precise about because of the numbers) were the rates of some specific cancers (eg prostate cancer).  There was amongst the 14641 men a subgroup of about 1300 men with a pre-existing history of cancer.

The results:

Men taking multivitamins had a modest reduction in total cancer incidence (HR, 0.92; 95% CI, 0.86- 0.998; P = .04)

My interpretation:  Those taking multivitamins were about 8% less likely to get cancer.  The statistics show that they are 95% confident that the amongst all men with the same characteristics as the men in their sample the true reduction in probability of getting cancer over the 11 year follow up period is between 0.2 and 14%.

A little frighteningly whilst major cardiovascular events were mentioned as part of the primary outcomes they were not reported on!

The strengths of the study are its size, that it is an RCT and double-blind, that it has good length, that all participants who received the multivitamin received the same one and that the multivitamin manufacturer had no role in designing or running the study, or analysing the data.

The weaknesses are that it is all men, all over the age of 50, and all physicians.

S0, is my faith justified?  If by that do you think I mean “proven” then think again. Proof or proven are words that should never be used in the company of good scientists.  Rather, I think there is some more good quality evidence to support the taking of multivitamins – so I shall continue to do so.  I must, though, remain open to evidence of the opposite variety and be aware that like all studies there is a probability that the conclusions will not be backed up by future studies.

Of course not all multivitamins are created equal (beware of fillers), they have different compositions and some are less likely to be absorbed than others, so do some homework before you rush out an buy some.

(1)  Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR. Dietary supplements and mortality rate in older women: the Iowa Women’s Health Study. Arch Intern Med 2011;171(18):1625–33.

(2) Gaziano JM. Multivitamins in the Prevention of Cancer in MenThe Physicians’ Health Study II Randomized Controlled TrialMultivitamins in the Prevention of Cancer in Men. JAMA : the journal of the American Medical Association 2012;:1.

[Conflict of interest:  My wife’s business includes the selling of multivitamin supplements]