Higher risk of womb cancer link to specific genetic variants

Author: Adrian O'Dowd

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Feb 18, 2020
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A large review of 149 scientific studies has identified 24 genetic variants that predispose women to endometrial (womb) cancer.

A study* published today in the Journal of Medical Genetics, details how researchers from the University of Manchester found that women with all or most of these variants could be two to three times more likely to develop the disease, which is the most common gynaecological cancer in the developed world.


There are about 8,600 new cases of this form of cancer per year in the UK.

Although each genetic variant, called single nucleotide polymorphysms (SNPs), changes cancer risk by a small fraction, when all 24 variants are combined in a so-called polygenic risk score, women who score within the top 1% have a risk of endometrial cancer more than three times higher than the average risk.

Previous research has implicated SNPs in womb cancer risk, but the quality of these studies varies considerably and they were mostly carried out before the advent of whole genome association studies.

Researchers led by Emma Crosbie, professor of gynaecological oncology from The University of Manchester, part of the NIHR Manchester Biomedical Research Centre (BRC), carried out what they described as the most comprehensive review so far of published evidence.

They looked at relevant research published between 2007 and 2018 to see if there was any association between SNPs and womb cancer risk and came up with 149 studies out of an initial 453.

From the relevant studies, they found that 24 common SNPs in or around six genes, coding for cell growth and death, the processing of oestrogen, and gene control factors (transcription control), were strongly associated with the development of womb cancer.

Nineteen of these genetic variants were statistically significant, while five were suggestive of disease risk, but they did not find any convincing evidence for the most widely studied (to date) genetic variant in womb cancer.

Women with most or all of these 24 genetic variants would be expected to be twice or three times as likely to develop womb cancer as those without, the researchers calculated.

There were likely to be more SNPs involved in womb cancer development, they added, saying that hundreds had been implicated in breast cancer, for example.

Professor Crosbie, BRC cancer early detection lead, said: “Manchester BRC’s cancer prevention and early detection research is helping transform the latest scientific breakthroughs in endometrial cancer, into lifesaving screening and treatments for patients.

“Because many of the studies carried out to date have been of variable quality, we felt it was important to understand more fully genetic predispositions to endometrial cancer. We hope our work will facilitate personalised risk assessment so that prevention and screening could be targeted more efficiently.”

The study’s authors concluded: “The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer.”


*Bafligil C, Thompson D J, Lophatananon A, et al. Association between genetic polymorphisms and endometrial cancer risk: a systematic review. Journal of Medical Genetics. DOI:10.1136/jmedgenet-2019-106529

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