It’s All in the Genes: ATM Pathogenic Variants in Cancer Risk

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Holly Magliochetti

Genetics Institute of America

Genetics Institute of America (GIA) is a national laboratory dedicated to heightening the awareness of early intervention and genetic screening to promote the longevity and quality of life outcomes.  


It’s All in the Genes:

Cancer Risk and ATM

DELRAY BEACH, FL  – ATM codes for a kinase, which is found in the cell nucleus. Its primary function is to control how fast cells proliferate within the body, as well as aid in DNA repair.1 ATM plays a vital role in the development of key body systems including the nervous system and immune system. Diminished function of the ATM protein could result in serious health conditions, including ataxia-telangiectasia and various types of cancer. 1 Pathogenic variants (PVs) within the ATM gene are fairly common within the population, even without family history; however, researchers are still attempting to understand the risk associated.

“Previous estimates of adult-onset breast cancer risk in women heterozygous for germline ATM PVs range from a 2- to 5-fold increased risk compared to women without ATM PVs. It has been suggested that there may be substantially higher risks associated with specific ATM variants…where the risk of developing breast cancer by age 70 has been estimated at 52- 60%.”2 A new study funded by the National Cancer Institute with researchers from Stanford University aimed to understand the magnitude of risk associated with ATM PVs in all cancer types. “Improved precision of estimates of cancer risks associated with ATM PVs is critical because ATM PVs are common in individuals of varied ancestry undergoing genetic testing for hereditary cancer risk, and even modest risk increases may warrant modified recommendations for [treatment,] cancer screening and prevention.”2

As a result of the data collected, the researchers found moderate-to-high risk associated with the following cancer types: invasive ductal breast, gastric, prostate, and pancreatic. Low-to-moderate risk was also seen for melanoma, colorectal cancer, ovarian cancer, male breast cancer, and ductal carcinoma. 2

These findings support increased risk for multiple cancer types associated with ATM PVs. Currently, guidelines support increased screening, prevention, and targeted treatment for breast and pancreatic cancer patients with an ATM PV; however, these same measures need to be extended to prostate and gastric cancer patients, as well.

  1. ATM gene. MedlinePlus. Accessed January 24, 2023.
  2. Hall MJ, Bernhisel R, Hughes E, et al. Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated (ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers. Cancer Prev Res (Phila). 2021;14(4):433-440. doi:10.1158/1940-6207.CAPR-20-0448
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