A positive correlation between random mutations in replicating cells and the onset of adult cancer was found at the Johns Hopkins Kimmel Cancer by Cristian Tomasetti and Bert Vogelstein.
That “bad luck”—that is, random mutations during DNA replication, environmental factors, and genetic disposition–contributes to cancer incidence is a well-known fact throughout the medical community. The findings of Tomasetti and Vogelstein are nevertheless groundbreaking because they quantify the contribution of random mutations, paving the way for a new understanding of cancer and its treatment.
The scientists predicted that because the mutation rate of all human cells is essentially the same, a correlation should exist between the number of divisions of stem cells in a particular organ and the risk of cancer arising in that same organ. To evaluate their hypothesis, they created a statistical model that compared the lifetime number of stem cell divisions in 31 organs with the risk of cancer in those organs. A statistically significant, positive correlation of 0.804 was found, substantiating the scientists’ claim.
A linear correlation equal to 0.804 suggests that 65% of the differences in cancer risk among different tissues can be explained by the total number of stem cell divisions in those tissues. Thus, the stochastic effects of DNA replication appear to be the major contributor to cancer in humans. (Tomasetti & Vogelstein, 2015)
Next, the scientists differentiated between the role of random mutations and that of genetics and the environment in cancer incidence. They studied two types of tumors, D-tumors, where the environment and inherited dispositions strongly affect their risk, and R-tumors, where tumors are minimally affected by deterministic factors. In both cases, they found that the effects of mutations in DNA replication are crucial to the onset of cancer.
“Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” says Vogelstein in a Johns Hopkins Medicine news release.
Vogelstein elucidates their findings by comparing cancer to getting into a car accident. A correlation between the length of a car trip and the probability of getting into an accident is analogous to the lifetime number of stem-cell divisions and the probability of cancer incidence.
While the notion that the major contributing factor to cancer is one out of humans’ control may be disheartening, its implications could revolutionize current cancer treatment. The study’s findings present an opportunity for the scientific world to make strides to better understand cancer and more accurately determine the best form of treatment.
There are two forms of cancer treatment: primary and secondary. Primary treatment consists of changing lifestyles and eliminating certain risk factors, such as quitting smoking. Secondary treatment is about prevention: detecting cancerous cells early and taking action against them. Certain cancer types will respond better to primary treatment and others to secondary treatment.
The revelation of the influence of mutations in stem-cells, combined with additional research, will help doctors dictate the ideal treatment for a particular cancer.
“Research on primary and secondary prevention, cancer treatment, and the biology of the disease is more important than ever,” says Tomasetti and Vogelstein in a Johns Hopkins Medicine news release.
Sources:
Johns Hopkins Medicine. (2015, January 1). ‘Bad luck’ of random mutations play predominant role in cancer, study shows. Science Daily. Retrieved January 11, 2015 from www.sciencedaily.com/releases/2015/01/150101142318.htm
Tomasetti, C., & Vogelstein, B. (2014). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science,347(6217), 78-81. Retrieved January 11, 2015, from http://www.sciencemag.org/content/347/6217/78.full
Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows. (2015, January 7). Johns Hopkins Medicine News and Publications. Retrieved January 11, 2015.
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