Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewed

Identification of nine new susceptibility loci for endometrial cancer

Tracy A. O’Mara, Dylan M. Glubb, Frédéric Amant, Daniela Annibali, Katie A. Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise A. Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang‐Claude, Stephen J. Chanock, Chu Chen, Maxine Chen, Timothy Cheng, Christine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous‐Bou, Kamila Czene, Felix R. Day, Joe Dennis, Jeroen Depreeuw, Jennifer A. Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny N. Fung, Montserrat García‐Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Høivik, Elizabeth Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loı̈c Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R. B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A. W. Rogers, Matthias Rübner, Ingo B. Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick R. Schumacher, Rodney J. Scott, Veronica Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao‐Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham

Nature Communications · 2018

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Summary

This meta-analysis of genome-wide association studies identified nine previously unknown susceptibility loci for endometrial cancer, doubling the number of established risk loci from eight to seventeen. Using data from over 12,900 endometrial cancer cases and 109,000 controls, the authors conducted eQTL analyses to identify candidate causal genes at five loci, notably implicating SH2B3 and NF1 as genes encoding negative regulators of oncogenic signalling. The findings provide a foundation for future functional studies and may inform understanding of endometrial cancer aetiology.

UK applicability

As a large-scale genetic association study, the findings are relevant to UK clinical and research populations, particularly for understanding inherited susceptibility to endometrial cancer. The identified loci may inform future risk stratification and screening strategies if translated into clinical practice, though the study itself is observational and does not address dietary or farming-system factors that might modify genetic risk.

Key measures

Genome-wide association test statistics; expression quantitative trait locus (eQTL) associations; odds ratios for risk alleles at novel loci

Outcomes reported

The study identified nine novel genome-wide significant loci associated with endometrial cancer risk through meta-analysis of 12,906 cases and 108,979 controls. Expression quantitative trait locus analyses at five loci revealed candidate causal genes, including SH2B3 and NF1, which encode negative regulators of oncogenic signalling proteins.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Meta-analysis
Study design
Meta-analysis
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41467-018-05427-7
Catalogue ID
SNmohdwa7i-t1h4wl

Topic tags

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