DNA copying errors increase cancer risk

The human body does not always run like a perfect machine. In fact, nearly two thirds of the mutations that lead to cancer are caused by the body’s arbitrary DNA copying mistakes.

This has historically been a cause of cancer that is largely neglected in the study of medicine. However, the development of a mathematical model that analyzes DNA sequencing helps to give a ballpark prediction of the percentage of copying errors that can result in a diagnosis of cancer.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer. But it is not as well-known that, each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes,” Cristian Tomasetti, an assistant professor of biostatistics at the Sidney Kimmel Comprehensive Cancer Center at and the Bloomberg School of Public Health, said in a press release.

According to Dr. Bert Vogelstein, co-director of the Ludwig Center at the Sidney Kimmel Comprehensive Cancer Center, many people would still face the possibility of developing cancer despite leading a healthy and regulated lifestyle.

This shows that DNA copying errors are genetic predispositions that play a vital role in the onset of cancer.

In a report published in the journal Science on March 24, Tomasetti and Vogelstein explained the details of their research.

Epidemiologic studies have shown that approximately 40 percent of cancer preventions can be successful in most cases.

However, it is surprising that patients who are diagnosed with cancer often belong to the category of people that has never touched cigarettes, drugs or any other form of carcinogens. Many of them also have a healthy weight and lifestyle.

This discovery prompts the further investigation of other possibilities that can culminate in cancer. Evidence of studies done by the research team confirms that in some cases random DNA copying errors are likely to occur no matter how many precautions are taken or how harmless the environment is.

For example, the researchers believe this phenomenon explains why certain cancers, such as colon cancer, might occur more frequently than other types of cancer.

In addition the research team extracts abnormal cell growth samples from 32 different types of cancer. Using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database, the researchers created a new model that is able to mathematically generate the percentage of pathological causes that contribute to the critical mutations. It is generally believed that two or more critical mutations are needed to cause cancer.

For example, pancreatic cancer has critical mutations that are comprised of 77 percent DNA copying errors, 18 percent environmental causes and five percent hereditary factors.

While examining the big picture researchers realized that there is a wide scope of variations in the leading causes of each type of cancer. The most noticeable difference is that between lung cancer and prostate, brain or bone cancer. While only 35 percent of mutations are caused by random copying mistakes in lung cancer, almost 95 percent of mutations are caused by this factor in the cases of prostate, brain or bone cancer.

The final conclusion reached by studying samples from the 32 cancer types is that approximately 66 percent of cancer mutations overall can be attributed to DNA copying errors.

Hence Tomasetti and Vogelstein stress the importance of using medical devices to detect cancerous DNA copying mistakes as early as possible.

“Typos will occur because no one can type perfectly. Similarly, mutations will occur, no matter what your environment is, but you can take steps to minimize those mutations by limiting your exposure to hazardous substances and unhealthy lifestyles,” Vogelstein said.

Tomasetti believes that random DNA copying errors will only become more important in the future as society faces increasing longevity and with it a higher chance for copying errors to occur as people age. Vogelstein hopes that this will increase awareness for the role of genetic copying mistakes in oncological development.