Scientists double number of known genetic risk factors for endometrial cancer

cjb250 — Tue, 03 May 2016 07:45:36 +0000

Endometrial cancer affects the lining of the uterus. It is the fourth most commonly diagnosed cancer in UK women, with around 9,000 new cases being diagnosed each year.

Researchers at the ̽��ֱ�� of Cambridge, Oxford ̽��ֱ�� and QIMR Berghofer Medical Research Institute in Brisbane studied the DNA of over 7,000 women with endometrial cancer and 37,000 women without cancer to identify genetic variants that affected a woman’s risk of developing the disease. ̽��ֱ��results are published today in the journal Nature Genetics.

Dr Deborah Thompson from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge said: “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. Prior to this study, we only knew of four regions of the genome in which a common genetic variant increases a woman’s risk of endometrial cancer.

“In this study we have identified another five regions, bringing the total to nine. This finding doubles the number of known risk regions, and therefore makes an important contribution to our knowledge of the genetic drivers of endometrial cancer.

“Interestingly, several of the gene regions we identified in the study were already known to contribute to the risk of other common cancers such as ovarian and prostate.

“Although each individual variant only increases risk by around 10-15%, their real value will be in looking at the total number of such variants inherited by a woman, together with her other risk factors, in order to identify those women at higher risk of endometrial cancer so that they can be regularly checked and be alert to the early signs and symptoms of the disease.”

̽��ֱ��study also looked at how the identified gene regions might be increasing the risk of cancer, and these findings have implications for the future treatment of endometrial cancer patients.

“As we develop a more comprehensive view of the genetic risk factors for endometrial cancer, we can start to work out which genes could potentially be targeted with new treatments down the track,” said Associate Professor Amanda Spurdle from QIMR Berghofer.

“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.”

̽��ֱ��study was an international collaboration involving researchers from Australia, the United Kingdom, German, Belgium, Norway, Sweden, the United States and China. ̽��ֱ��UK part of the study received funding from Cancer Research UK.

Dr Emma Smith, Cancer Research UK’s science information manager, said: “ ̽��ֱ��discovery of genetic changes that affect women’s risk of developing endometrial – or womb – cancer could help doctors identify women at higher risk, who could benefit from being more closely monitored for signs of the disease.

“It might also provide clues into the faulty molecules that play an important role in womb cancer, leading to potential new treatments. More than a third of womb cancer cases in the UK each year could be prevented, and staying a healthy weight and keeping active are both great ways for women to reduce the risk.”

Reference
Cheng, THT et al. Five endometrial cancer risk loci identified through genome-wide association analysis. Nature Genetics; 2 May 2016; DOI: 10.1038/ng.3562

An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.

Interestingly, several of the gene regions we identified in the study were already known to contribute to the risk of other common cancers

Deborah Thompson

Andy Leppard

DNA representation (cropped)

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Maintaining healthy DNA delays menopause

sc604 — Mon, 28 Sep 2015 15:02:45 +0000

̽��ֱ��findings, published today (September 28) in the journal Nature Genetics, suggest that the reproductive cells or ‘eggs’ in a woman’s ovaries (known as oocytes) that repair damaged DNA more efficiently survive longer. This results in a later age at menopause, which marks the end of a woman’s reproductive lifetime. Previous research has shown that DNA is regularly damaged by age and by toxic substances such as cigarette smoke - hence women who smoke go through menopause 1-2 years earlier on average than non-smokers.

Our cells have many mechanisms to detect and repair such damage, but cells die when too much damage accumulates. DNA is also damaged and repaired during the production of eggs – therefore these genes might also act to enhance a woman’s pool of eggs which is set in early life.

In a collaboration involving scientists from 177 institutions worldwide, the authors undertook a genome-wide association study of almost 70,000 women of European ancestry.

“Many women today are choosing to have babies later in life, but they may find it difficult to conceive naturally because fertility starts to diminish at least 10 years before menopause,” said Dr Anna Murray from the ̽��ֱ�� of Exeter, and the paper’s senior author. “Our research has substantially increased our understanding of how reproductive ageing in women happens, which we hope will lead to the development of new treatments to avoid early menopause.”

Dr John Perry from the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge co-led the study, and said: “We have known for some time that the age at which women go through menopause is partly determined by genes. This study now tells us that there are likely hundreds of genes involved, each altering menopause age by anything from a few weeks to a year. It is striking that genes involved in DNA repair have such an important influence on the age of menopause, which we think is due to their effect on how quickly a woman’s eggs are lost throughout her lifetime.”

̽��ֱ��researchers also used these genetic findings to examine links between menopause and other health conditions. They predict that every one year later that menopause occurs increases the risk of developing breast cancer by 6%.

Dr Deborah Thompson from the Department of Public Health and Primary Care at the ̽��ֱ�� of Cambridge also co-led this large international collaboration and said: “One particularly convincing finding was that going through menopause earlier reduces your chances of developing breast cancer and we think this is because these women have less exposure to the hormone oestrogen over their lifetime.”

̽��ֱ��next step is to understand in more detail how the genetic variations found in this study are causing alterations in the timing of menopause. Uncovering these mechanisms will hopefully lead to better treatment for conditions linked to menopause, such as infertility and also improved understanding of the heath impact of menopause, such as risk of osteoporosis and heart disease.

Menopause usually occurs between ages 40 to 60 years old, indicated by the end of natural menstrual cycles and in many women by physical symptoms, such as hot flushes, disrupted sleep, and reduced energy levels. Natural menopause before the age of 40 is often called “primary ovarian insufficiency” and occurs in 1% of women.

Adapted from a ̽��ֱ�� of Exeter press release.

Reference:
Felix R Day et al. 'Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.' Nature Genetics (2015). DOI: 10.1038/ng.3412.

An international study of nearly 70,000 women has identified more than forty regions of the human genome that are involved in governing at what age a woman goes through menopause. ̽��ֱ��study, led by scientists at the Universities of Cambridge and Exeter, found that two thirds of those regions contain genes that act to keep DNA healthy, by repairing the small damages that can accumulate with age.

We have known for some time that the age at which women go through menopause is partly determined by genes. This study now tells us that there are likely hundreds of genes involved

John Perry

Ed Uthman

Human egg

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̽��ֱ�� of Cambridge - Deborah Thompson

Scientists double number of known genetic risk factors for endometrial cancer

Maintaining healthy DNA delays menopause