Randomness

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Random mutations play large role in cancer, study finds

GROWING PAINS As cells divide and grow to replenish and repair organs, accidental mutations may crop up in cancer-associated genes. A new study suggests such random mistakes are the source of 66 percent of mutations in cancer cells (illustrated here) across the board.

Researchers have identified new enemies in the war on cancer: ones that are already inside cells and that no one can avoid.

Random mistakes made as stem cells divide are responsible for about two-thirds of the mutations in cancer cells, researchers from Johns Hopkins University report in the March 24 Science. Across all cancer types, environment and lifestyle factors, such as smoking and obesity, contribute 29 percent of cancer mutations, and 5 percent are inherited.

That finding challenges the common wisdom that cancer is the product of heredity and the environment. “There’s a third cause and this cause of mutations is a major cause,” says cancer geneticist Bert Vogelstein.

Such random mutations build up over time and help explain why cancer strikes older people more often. Knowing that the enemy will strike from within even when people protect themselves against external threats indicates that early cancer detection and treatment deserve greater attention than they have previously gotten, Vogelstein says.

Vogelstein and biomathematician Cristian Tomasetti proposed in 2015 that random mutations are the reason some organs are more prone to cancer than others. For instance, stem cells are constantly renewing the intestinal lining of the colon, which develops tumors more often than the brain, where cell division is uncommon. That report was controversial because it was interpreted as saying that most cancers are the result of “bad luck.” The analysis didn’t include breast and prostate cancers. Factoring in those common cancers might change the results, some scientists said. And because the researchers looked at only cancer within the United States, critics charged that the finding might not hold up when considering places around the world where different environmental factors, such as infections, affect cancer development.

In the new study, Vogelstein, Tomasetti and Hopkins colleague Lu Li examined data from 69 countries about 17 types of cancer, this time including breast and prostate. Again, the researchers found a strong link between cancer and tissues with lots of dividing stem cells. The team also used DNA data and epidemiological studies to calculate the proportions of mutations in cancer cells caused by heredity or environmental and lifestyle factors. Remaining mutations were attributed to random errors — including typos, insertions or deletions of genes, epigenetic changes (alterations of chemical tags on DNA or proteins that affect gene activity) and gene rearrangements. Such errors unavoidably happen when cells divide.

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Chance cancer

For many organs, more of the mutations that lead to cancer come from random mistakes in DNA…