Recent research has uncovered six genes that influence cancer risk.
Using extensive genetic datasets, the study pinpointed specific genes linked to both increased and decreased cancer risks, offering new paths for cancer prevention and therapy.
Discovery of New Cancer Susceptibility Genes
Scientists at deCODE genetics and Amgen, along with collaborators, have identified six new genes with rare germline variants linked to cancer risk. Their research, published today (October 29) in Nature Genetics under the title “Gene-based burden tests of rare germline variants identify six cancer susceptibility genes,” marks a significant advancement in understanding genetic factors in cancer susceptibility.
Some cancers occur in individuals with rare genetic variants that considerably heighten their risk. Discoveries of such variants, as seen in the BRCA1 and BRCA2 genes, have revolutionized early cancer detection and enabled the creation of targeted therapies. These advancements have ultimately reduced cancer rates and improved outcomes for individuals with these genetic predispositions.
Analysis of Genetic Data for Cancer Risks
In this study, the scientists analyzed three large genetic datasets from individuals of European descent, including 130,991 cancer patients and 733,486 controls. Through a gene-based burden association analysis across 22 different cancer types, they found four novel genes associated with a risk of developing cancer; the pro-apoptotic BIK for prostate cancer, the autophagy involved ATG12 for colorectal cancer, TG for thyroid cancer, and CMTR2 for both lung cancer and cutaneous melanoma.
The relative increase in cancer risk conferred by these variants was substantial (90-295%), but it should be noted that the design of the study does not allow an accurate assessment of absolute lifetime cancer risk.
Protective Genetic Variants Against Cancer
Additionally, the researchers found the first genes with rare variants that are associated with a decreased risk of cancer. Specifically, loss of AURKB was found to protect against any cancer type, and loss of PPP1R15A was associated with a 53% lower risk of breast cancer. This suggests that inhibition of PPP1R15A may be a therapeutic option for breast cancer.
The study revealed new insight into the biological mechanisms involved in cancer predisposition that will hopefully lead to better screening and treatment strategies.
Reference: “Gene-based burden tests of rare germline variants identify six cancer susceptibility genes” by Erna V. Ivarsdottir, Julius Gudmundsson, Vinicius Tragante, Gardar Sveinbjornsson, Snaedis Kristmundsdottir, Simon N. Stacey, Gisli H. Halldorsson, Magnus I. Magnusson, Asmundur Oddsson, G. Bragi Walters, Asgeir Sigurdsson, Saedis Saevarsdottir, Doruk Beyter, Gudmar Thorleifsson, Bjarni V. Halldorsson, Pall Melsted, Hreinn Stefansson, Ingileif Jonsdottir, Erik Sørensen, Ole B. Pedersen, Christian Erikstrup, Martin Bøgsted, Mette Pøhl, Andreas Røder, Hein Vincent Stroomberg, Ismail Gögenur, Jens Hillingsø, Stig E. Bojesen, Ulrik Lassen, Estrid Høgdall, Henrik Ullum, Søren Brunak, Sisse R. Ostrowski, DBDS Genomic Consortium, Ida Elken Sonderby, Oleksandr Frei, Srdjan Djurovic, Alexandra Havdahl, Pal Moller, Mev Dominguez-Valentin, Jan Haavik, Ole A. Andreassen, Eivind Hovig, Bjarni A. Agnarsson, Rafn Hilmarsson, Oskar Th. Johannsson, Trausti Valdimarsson, Steinn Jonsson, Pall H. Moller, Jon H. Olafsson, Bardur Sigurgeirsson, Jon G. Jonasson, Geir Tryggvason, Hilma Holm, Patrick Sulem, Thorunn Rafnar, Daniel F. Gudbjartsson and Kari Stefansson, 29 October 2024, Nature Genetics.
DOI: 10.1038/s41588-024-01966-6
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.