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The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.
“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.
The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.
The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.
After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.
The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).
“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.
They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.
“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,” the researchers concluded.
The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.
SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.