Summary

Scientists at deCODE genetics/Amgen and their collaborators have identified six new genes with rare germline variants linked to cancer risk, published in Nature Genetics.

Takeaways

  1. Gene Discovery: Six novel cancer susceptibility genes were identified, including BIK for prostate cancer and ATG12 for colorectal cancer.
  2. Large-Scale Analysis: The study involved analyzing genetic data from 130,991 cancer patients and 733,486 controls of European descent.
  3. Decreased Cancer Risk: Rare variants in genes like AURKB and PPP1R15A were found to decrease cancer risk, offering potential new therapeutic targets.

Scientists at deCODE genetics/Amgen, and their collaborators have discovered six novel genes with rare germline variants that associate with cancer risk. The findings are published today in Nature Genetics under the title “Gene-based burden tests of rare germline variants identify six cancer susceptibility genes”.

Rare Variants Point to Cancer Risk

A subset of cancers arises in individuals who are born with rare sequence variants that significantly alter their cancer risk. The discovery of such variants, like those in the BRCA1– and BRCA2 genes, has led to improved early cancer detection and the development of targeted therapies, ultimately reducing the cancer burden and improving prognosis of those carrying these mutations.

Cancer Risk Analyzed in Three Large Genetic Datasets

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 cancer risk; 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 accurate assessment of absolute lifetime cancer risk.

Decreased Risk Also ID’d

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 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.

Featured Image: Kari Stefansson CEO of deCODE genetics and senior author and Erna V. Ivarsdottir first author on the paper. Photo: Jon Gustafsson/deCODE Genetics