Scientists: Random gene mutations primary cause of cancer

Ever marvel at someone who smoked and still lived to be 90? Just plain good luck, researchers say. And those who live like Puritans and get cancer anyway?

That’s bad luck — and it’s the primary cause of most cancer, says a Johns Hopkins Medicine research study.

Roughly “two-thirds of cancer incidence” in adults can be attributed to random mutations in genes capable of driving cancer growth, said two scientists who ran statistics on cancer cases.

That may sound jaw-dropping. And Johns Hopkins anticipates that the study will change the way people think about cancer risk factors.

They also believe it could lead to changes in the funding of cancer studies, with a greater focus on finding ways to detect those cancers attributed to random mutations in genes at early, curable stages.

Smoking can still kill you

But, no, that’s not permission to smoke or to not use sunblock.

Some forms of cancer are exceptions, where lifestyle and environment play a big role. Lung cancer is one of them. So is skin cancer.

And, if cancer runs in your family, this unfortunately doesn’t mean you’re in the clear. Some cancers are more strongly influenced by genetic heritage than others.

“The remaining third (of cancer incidences) are due to environmental factors and inherited genes,” the Kimmel Cancer Center said in a statement on the study published Friday in the magazine Science.

In fact, all three factors work together.

“All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development,” said cancer researcher Bert Vogelstein.

Compounding matters

An unhealthy lifestyle can compound matters, but more for some cancers than for others, the scientists said.

“Changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” medical statistician Cristian Tomasetti said.

He placed heavy emphasis on early detection.

Stem cells in our organs divide constantly to replenish damaged tissue. Sometimes there are random mistakes in the replication of DNA, small mutations, Vogelstein said.

Some genes, when they mutate, are more apt to promote cancer growth.

“The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer,” Vogelstein said.

Scientist have known this for a long time, but what the study reveals was how big of an influence it is.

“The actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors, was not previously known,” says Vogelstein.

Dr. Otis Brawley, chief medical officer for the American Cancer Society, told CNN the study was “good science” that backed up what many scientists already thought.

“This is actually just confirmation of something that we have known for probably 20 years,” he said.

“As we have learned more and more about cancer … we’ve come to realize that a number of cancers start purely because of mutations that happen that are just unexplainable. Bad luck is, unfortunately, the right way to explain it.”

Those cancers that develop have escaped at least three fail-safe systems in the body that deal with these cell mutations, he said; these are programmed cell death, or apoptosis, DNA repair enzymes and certain cells in the immune system.

Cell division and statistics

For their study, the two scientists came up with an average total number of cell divisions in 31 different tissues within a human lifetime. And they looked at the cancer risk in each of those tissues.

They determined that the more a tissue’s cells divide, the higher the chance cancer could develop in that tissue.

“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.

Colon tissue, for example, divides much more than other intestinal tissue, and cancer in the colon is much more prevalent there, the study said.

With colon tissue, the scientists took environmental influences into account.

Doing the math overall, the two scientists arrived a rate at which cancer risk can be explained by the cell divisions. It was 65 percent, they said.

Lung and skin cancer

The researchers drew a line between one group of cancers and another. Of the 31 they looked at, they determined that 22 were basically “bad luck” cancers.

Nine others appeared at rates noticeably higher than could be expected from cell division alone. Researchers said habits, pollution or genetics also strongly influence cancer in these tissues.

No surprise: Lung cancer and skin cancer were two of them, they said. Smoking and too much sun exposure are still strongly linked to those cancers.

But people who don’t smoke and avoid the sun can still get them — as “bad luck” cancers, the study said.

“It is important to emphasize that the nine cancers where non-random events are important, these constitute the most prevalent cancers,” said Dr. Gordon Mills, chair of systems biology and co-director of the Institute for Personalized Cancer Therapy at the University of Texas MD Anderson Cancer Center.

“Thus, the major it (sic) of cancers likely have joint random mutation and hereditary events,” he said.

Lung, breast, ovarian, prostate and colorectal cancers — variations of the disease in which hereditary or environmental factors contributed to tumor growth — are some of the most common types of cancers, he said.

“If one was to ask about the number of cancers — not cancer types — you would have to say that many of those cancers have an environmental effect,” Mills said.

Lifestyle

Brawley said the study’s findings should be no reason to alter behaviors shown to lessen the risk of cancer.

“We have good epidemiological data to show that people can reduce their risk of cancer and I would encourage them to do those things,” he said.

They include not smoking, managing their weight so they don’t become obese and taking physical exercise, he said.

As for the suggestion the study’s findings may prompt changes in funding, Brawley said he would be pleased just to see more money go into research.

“Only 10% of the grants submitted to the NIH (National Institutes of Health) actually get funded because we have such a shortage of money,” he said.

“We invested in the United States last year $5 billion in cancer research. I would like to see more.”

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