Endometrial cancer: Study doubles clues to genetic risk

An international study has identified five new gene regions – bringing the total of known regions to nine – that increase a woman’s risk of developing endometrial cancer.
gene markers
As researchers gather more comprehensive data on the risk factors for endometrial cancer, then it becomes clearer which genes can be targeted with new treatments.

The team of researchers – from Australia, Belgium, China, Germany, Norway, Sweden, the United Kingdom, and the United States – reports the findings in the journal Nature Genetics.

Endometrial cancer is cancer that develops in the uterus when cells in its inner lining (the endometrium) grow out of control.

For the study, the team pooled data from genome-side association studies that altogether investigated the DNA of over 7,000 women with endometrial cancer and 37,000 women without cancer.

They identified genetic variants that affect the risk of developing the disease.

The investigators identified five new gene regions that were not previously associated with endometrial cancer, although some of them are already known to contribute to risk of developing ovarian, prostate, and other common cancers.

The findings bring the total number of gene regions that appear to raise the risk of developing endometrial cancer to nine – over double the previous number.

One of the authors, Dr. Deborah Thompson from the University of Cambridge in the U.K., says:

“Our findings help us to paint a clearer picture of the genetic causes of endometrial cancer in women, particularly where there no strong family history of cancer.”

Risk genes could be targeted with new treatments

Dr. Thompson explains that while each individual variant only appears to raise the risk of disease by 10-15 percent, their real value will be in helping to find the total number of such variants women might have inherited.

Combined with other risk factors, this can identify those women at higher risk who should perhaps have regular checks.

The researchers also examined which mechanisms might link the identified gene regions to disease, which could help develop treatment that targets the mechanisms. They note their findings “provide enhanced insight into the genetic and biological basis of endometrial cancer.”

For example, one gene region they identified appears to interact with a mechanism that affects the expression of KLF5 – a gene thought to be active during the development of the uterus.

The authors suggest perhaps altering expression of this gene could contribute to the development of endometrial cancer.

Study co-author Amanda Spurdle, an associate professor at QIMR Berghofer Medical Research Institute in Brisbane, Australia, says as researchers gather more comprehensive data on the risk factors for endometrial cancer, then it becomes clearer which genes can be targeted with new treatments.

“In particular, we can start looking into whether there are drugs that are already approved and available for use that can be used to target those genes.”

Prof. Amanda Spurdle

According to the American Cancer Society, endometrial cancer is the most common cancer of the female reproductive organs in the U.S., where estimates suggest 60,050 new cases will be diagnosed in 2016.

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