New gene changes linked to greater risk of brain and ovarian cancer

Genetic changes and variants linked to the development of brain and ovarian cancers have been discovered in two new studies. This significant development offers researchers the chance to understand more about how these cancers develop and how they may one day be treated, or even prevented.

The two studies, published Tuesday, scanned the genomes of tens of thousand of individuals with and without these forms of cancer and revealed 13 new gene mutations linked to increased risk of glioma – the most common form of brain cancer – and 12 new gene variants, or types, that increase the risk of developing ovarian cancer.

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Identifying these changes could help predict someone’s chances of developing these cancers with greater accuracy, the researchers say.

One of the genetic changes discovered increases risk of brain cancer by as much as a third, with the rest by at least 15%.

More than 22,000 women in the United States are estimated to be diagnosed with ovarian cancer in 2017, according to the American Cancer Society, and more than 80,000 men and women with some form of primary brain tumor, with almost a quarter of those classed as gliomas, according to the American Brain Tumor Association (ABTA). The ABTA estimate three-quarters of malignant brain tumors are gliomas.

“In cancer research, we want to really understand the disease,” said Dr. Karoline Kuchenbaecker, Statistical Geneticist at the University of Cambridge who led the Ovarian cancer analysis.

“Then we can develop treatment and predict risk in women,” she said.

Added risk of ovarian cancer

The causes of ovarian cancer are not fully understood but age, obesity, pregnancies and birth control are thought to both increase and decrease risk, as well as family history of the disease, according to the American Cancer Society.

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“We know ovarian cancer is heritable to some extent,” said Kuchenbaecker, “probably due to many (gene) variants and we don’t know what they are specifically.”

In their study, the team at Cambridge scanned the genomes of nearly 100,000 people, consisting of women with and without ovarian cancer as well as women carrying mutations in their BRCA1 and BRCA2 genes – known to increase risk of both breast and ovarian cancers.

Prior to the new study, 23 gene variants were already known to be linked to an increased risk of ovarian cancer, said Kuchenbaecker. This study identified an additional12.

“We found new genes that are likely to be implicated in the development of ovarian cancer,” said Kuchenbaecker.

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She added that the newly identified mutations will be particularly useful for calculating the extra risk faced by women with existing mutations in their BRCA1 and BRCA2 genes, which are commonly identified through family screening when someone is diagnosed with breast or ovarian cancer.

The previously known mutations are known to increase lifetime risk of developing ovarian cancer from 6% to 19%, said Kuchenbaecker.

The team now plans to calculate the added risk posed by the newly identified gene changes. “We can use these variants to refine the risk assessments for these women,” she said, but added that the new insight will also help calculate the lifetime risk for all women known to have a family history of the disease.

“If the newly identified changes are confirmed, finding out how these can lead to ovarian cancer could support research into developing new drugs and lead to more personalized treatments for the disease,” said Dr. Justine Alford, Cancer Research UK’s senior science information officer. “As the outlook for ovarian cancer is often poor, we urgently need to find new ways to prevent, diagnose and treat the disease.”

Newly identified mutations for brain cancer

Unlike the case withovarian cancer, in brain cancer,gene changes or variants were yet to be known that definitively influenced the risk of someone developing a glioma.

Gliomas are not a specific type of brain cancer, but instead a general term for tumors that develop in the brain’s glial cells – that surround and support nerve cells.

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“Gliomas are not common, but in middle age they are not uncommon,” said Dr. Richard Houlston, professor of molecular and population genetics at the Institute of Cancer Research who led the new research to identify gene changes. “And there are no robust environmental risk factors,” he said.

There is currently no effective way of detecting this form of cancer early and current treatments are not that effective, the study highlights.

By scanning the genomes of more than 30,000 people with and without gliomas, scientists at the Institute of Cancer Research in the UK looked for mutations in DNA that could be linked to an increased risk of developing this form of cancer.

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They discovered 13 previously unknown changes to genes linked to an increased risk of developing aglioma. The changes were found to impair various functions within the cells, including the division of nerve cells and their inflammation and ability to produce proteins.

The changes were also discovered to differently impact the two forms of glioma, known as glioblastoma and non-gliobastoma, the former of which is particularly aggressive, with an average survival of 10 to15 months after diagnosis. One mutation – found on a gene called HEATR3 and thought to affect risk of this more severe form of cancer – was estimated to increase risk by as much as 18%.

“We now have a greater understanding of the biological basis of the disease,” said Houlston. “There are some variants that are more influencing.”

Houlston would like to now use the new insight to better understand how these tumors form and eventually help develop new tests or therapies.

The findings might also one day help people with a family history become better informed about their risk of developing a brain tumor so they can be aware of any signs of the disease. “This may inform better therapy, but at the moment it’s quite early to think about that,” he said.

“We urgently need to find new ways to tackle hard-to-treat cancers like brain tumors. Finding new genetic changes linked to brain tumors could give us important new clues about how and why these cancers develop,” said Dr. Catherine Pickworth, Cancer Research UK’s science information officer.

“The next steps will (be) finding out if any of these clues help to develop effective treatments for people with brain tumors.”