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Risk, Randomness and Cancer

Posted By Prucia Buscell, Thursday, January 08, 2015

The risk of developing many kinds of cancer may rely on random luck.

Cristian Tomasetti, PhD, and Bert Vogelstein, MD, cancer scientists at Johns Hopkins University School of Medicine, report in a Science magazine article that many cancers are caused by random mutations that happen when healthy stem cells divide. Cancers are known to result from life styles, inherited proclivities, and environmental exposures, as well as causes that can't be identified. A New York Times story by Denise Grady reports that the authors found chance was a bigger factor than they'd expected. "It was about double what I would have thought," Dr. Tomasetti, a biostatistician and professor told the Times. Basically, the risk of cancer is highly correlated with the number of stem cell divisions over time.

A Johns Hopkins press release explains that Tomasetti and Vogelstein charted the number of stem cell divisions likely to occur in 31 tissue types during an average life span, and compared these rates with the lifetime risk of cancer in the same tissues among adult Americans. Adult stem cells are a specialized population of cells in each organ or tissue that divide or self-renew indefinitely to generate replacement parts as other cells wear out.

The researchers report, for example, that the large intestines have more stem cells than small intestines, and those cells divide 73 times a year, compared with cells in the small intestines that divide 24 times a year. The lifetime risk of cancer in the large intestine is 4.8 percent, which is 24 times higher than the risk of a small intestine cancer. Their calculations show that about two thirds of the variation in cancer risk was explained by the number of stem cell divisions, and about one third is explained by heredity and environment.

They compare cancer with a car accident. The longer the trip, the higher the risk of accident. They say the mechanical condition of the car is a metaphor for inherited genetic factors and road conditions are like environmental factors. We may not know which of these three conditions contributed most to a particular wreck, but well maintained roads and vehicles can reduce overall risks. Knowledge that some factors are beyond our control may reduce stigma and comfort some cancer patients who blame themselves for their illness. Findings also suggest more cancers will appear simply because aging increases the number of stem cell divisions, the authors say in the release, so research on early detection, treatment and the biology of the disease is more important than ever.

Breast and prostate cancers were not included in the study because researchers lacked data on breast and prostate stem cell division rates. Lung cancer cases were divided between smokers and non-smokers, leading some readers to note that smoking also contributes to many other cancers. The American Lung Association reports that smoking causes nearly 90 percent of all lung cancer cases.

In a lengthy blog post on the article, oncologist David Gorski, MD, cites research suggesting one third to one half of all cancers are "potentially preventable," meaning they come from environmental factors that could be altered, such as smoking, alcohol use and weight control. He has some quibbles with the article, and wishes the discussion of it had been more nuanced. Bob O'Hara and GirrlScientist writing in The Guardian complain that too many news stories about the research confuse the variation in cancer risk with absolute risk of cancer, thereby blurring what constitutes bad luck.

Sometimes luck is randomly good. In the press release, Dr. Vogelstein observes cancer free longevity in people exposed to tobacco smoke and other carcinogens, often attributed to good genes, is likely to be good luck.

Tags:  buscell  complexity matters  culture  disease  health  luck  research 

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