Risk factors for endometrial cancer

The systematic review, led by Professor Emma Crosbie from The University of Manchester, could help scientists develop targeted screening and prevention strategies for women at greatest risk of the disease.

Although each genetic variant 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 3.16 times higher than the mean risk they say.

Published in the Journal of Medical Genetics, the study is the most comprehensive systematic review carried out to critically appraise the evidence on genetic variants implicated in predisposition to endometrial cancer.

The team was based at The University of Manchester, University of Cambridge and Manchester University NHS Foundation Trust and was funded by the NIHR Manchester Biomedical Research Centre.

The research is an important milestone in the study of endometrial cancer, the sixth most commonly occurring cancer in women and the 15th most commonly occurring cancer overall according to the World Cancer Research Fund.

In the UK there are about 8,600 new cases per year according to Cancer Research UK.

The team searched 2,674 abstracts, narrowing them down to 149 papers which were eligible for inclusion in the study.

Specifically, genetic variants in HNF1B, KLF, EIF2AK, CYP19A1, SOX4 and MYC were strongly associated with the cancer.

Nineteen variants were reported with genome-wide significance and a further five with suggestive significance.

They found no convincing evidence for the widely studied MDM2 variant rs2279744 as a risk factor.

"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," said Professor Crosbie.

"Our work, we hope, will facilitate personalized risk assessment so that prevention and screening could be targeted more efficiently."

She added: "These genetic variants linked to endometrial cancer risk are involved in cell survival, estrogen metabolism and transcriptional control -- when the information stored in our DNA is converted into instructions for making proteins or other molecules.

"We think studies with larger cohorts are needed to identify more variants with genome-wide significance.

"But until data from larger and more diverse cohorts are available, these twenty-four SNPs are the most robust common genetic variants that affect endometrial cancer risk."