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Inflammation: From Mummies to Melanoma

Thu, 03/21/2013 - 1:46pm
Cynthia Fox

Anti-inflammatory drugsInflammation is stirring up headlines again. Anti-inflammatory aspirin prevented thousands more cancers. The anti-inflammatory “miracle molecule” resveratrol came back. Psychologists report inflammation is stoked by even minor tensions. And archaeologists say all this knowledge is long overdue, as even Egyptian mummies have clogged arteries.

We have been plagued by inflammation since the time of the Pharaohs.

The cancer news roused the biggest response. A Stanford University study found aspirin wards off melanoma in a “quite significant” way, says George Trinchieri, the National Cancer Institute’s Cancer and Inflammation Program Director.

In September, a Science writer had waxed enthusiastic over three Lancet analyses finding aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) taken regularly can fend off many cancers—and retard others. “The first proof of principle that a simple compound of any kind can reduce the risk of several cancers,” Oxford University’s Peter Rothwell told Science, noting he took daily aspirin as a prophylactic.

Science said top researchers were close to advising cancer be added to indications for daily aspirin use, but sought more data.

This week, Stanford provided more, showing on March 11 in Cancer that among 60,000 post-menopausal women, regular aspirin use was associated with a decrease in melanoma risk of 21 percent.1 There was an 11 percent risk reduction at one year; a 22 percent risk reduction between one and four years; a 30 percent risk reduction at five years plus.

Given recent trends, there was only one surprise, says lead investigator Jean Tang: “We did not see an effect of (non-aspirin) NSAID for protection.” Some say there were too few non-aspirin NSAID users in the study. Others note aspirin’s anti-cancer record is better generally.

Regardless, says Trinchieri: “The effect is quite significant for melanoma and a few others, particularly GI tract tumors. These studies clearly bring us closer to considering “an aspirin a day” advisable for cancer protection, combined with the cardiovascular effect.”

Trinchieri cautions aspirin can cause internal bleeding. But this can subside after long-term use, fortunate since “the anticancer effect seems to be dependent on very long-term use.” For heart patients at risk for certain cancers, an “aspirin a day” may soon be mantra. A caveat: while “aspirin obviously has at least initially a significant protective effect for major cardiovascular events” this can wear off over time, yet the cancer effect builds over time.

But the list of cancers affected by aspirin is growing. Beyond melanoma, there is lung, brain, prostate, colorectal and other gastrointestinal cancers, he says. More study for “deeper understanding” is warranted—and coming.

The recent data were drawn from the Women’s Health Initiative, a study of many diseases, enrolling women aged 50-79 who shared their diet, activity, medication, and sun exposure habits. While the earlier, 40,000-strong Women’s Health Study found no cancer protection for aspirin (outside of lung cancer), its women only took it every other day. The earlier Lancet studies included a meta-analysis of 51 randomized trials in which daily aspirin was linked to 37% fewer deaths from many cancers after 5 years.

Fittingly, the anti-inflammatory “miracle molecule” resveratrol returned this week, too. Resveratrol made headlines in 2003, when Harvard University’s David Sinclair found the red wine compound activated sirtuins, extending life in flies, worms, and mice. Sinclair, like Rothman, was so confident of his pill he took it as a prophylactic. GlaxoSmithKline was so confident it bought his Sirtris Pharmaceutical in 2008 for $720 million.

A pall was cast over the work when other labs failed to duplicate it. But Sinclair now reports resveratrol indeed activates sirtuins, if under certain conditions.2 The results need to be replicated. And GSK continued with plans to close the company’s Cambridge shop.

But the study is strong enough Americans may soon be happily toasting to—not just with—red wine again.

Not all news has been good. Ohio University psychologist Peggy Zoccola was due to tell the American Psychosomatic Society March 15 that when adults were asked to just think about a stressful incident, their levels of inflammatory C-reactive protein rose.

The study is the first to directly measure this effect in the body. It points to the difficulty of stamping out inflammation.

But it may all be a matter of perspective. Randall Thompson of St. Luke’s Mid America Heart Institute reports in The Lancet that CT scanning of mummies from Egyptian, Peruvian, Ancestral Puebloan, and Unangan populations, disparate regions and eras, showed many had clogged arteries, or atherosclerosis.3 That is, 47 (34%) of 137 mummies had probable or definite atherosclerosis. Of those, 17 (39%) of 44 mummies were female and 30 (39%) of 77 were male.

“A wealth of evidence points to a key role for inflammation in both circulatory and malignant processes,” wrote Manchester University cardiologist Anthony Heagerty in a commentary.4 “High levels of chronic infection and inflammation could have promoted cardiovascular lesion development and, although not being fatal for most, might have become so with the passage of time. These data confirm that atheroma has been a burden on the human circulation for centuries.”

Still, modern couch potatoes can live to 80 before expiring. The mean age of death was 36 for the ancient couch potatoes. Surely the next 4,000 years will bring even more progress to the inflammation field.

 

References

1. Gamba, C.A. et al., “Aspirin is Associated With Lower Melanoma Risk Among Postmenopausal Caucasian Women,” Cancer, Published Online March 11, 2013.

2. Hubbard, B., et al., “Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators,” Science, Published Online March 8, 2013.

3. Thompson R.C., et al., “Atherosclerosis across 4000 years of human     history: the Horus study of four ancient populations,” The Lancet, Early Online Publication, March 10, 2013.

4. Heagerty, A., “Scanning ancient history for evidence of modern diseases,” The Lancet, Early Online Publication, March 11, 2013

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