ATM-Related Cancer Risk

The ATM gene plays an important role in cell growth and protection against DNA damage.

The ATM gene is classified as a “moderate risk” gene, meaning that there is a modestly increased risk for certain types of cancers.  For example, women who have one ATM pathogenic gene mutation likely have an approximately 3-fold increased risk of breast cancer as compared to the general population. ATM gene mutations have also been linked to an increased risk for pancreatic and prostate cancer, but the lifetime risks for these types of cancer are not yet defined.  Further research is needed to understand the interactions of moderate risk genes and family history on lifetime cancer risk.

Rarely, an individual will inherit two ATM gene mutations – one from each parent.  When this happens, the child has a severe disease called Ataxia Telangiectasia (AT).  Children who have AT have neurological problems, immunodeficiency, and cancers such as leukemia and lymphoma.  Most children are diagnosed with AT between the ages of 1 to 4 years.

ATM cancer screening and risk-reducing options

There is currently no agreement within the medical community on the best long-term medical management for an individual who carries a mutation in the ATM gene.  Healthcare providers oftentimes rely on an individual’s personal and family history to guide medical care.

Depending upon personal and family history, some women may consider increased breast cancer surveillance such as mammogram and breast MRI.

At this time, there is no proven form of screening for pancreatic cancer. Some hospitals may offer research-based screening with imaging exams (MRI, CT, and endoscopic ultrasound) and blood work.  Potential benefits, risks and limitations of research-based screening should be understood.

Depending upon personal and family history, some men may consider increased prostate cancer surveillance such as PSA blood testing and digital rectal examination.

As research continues to evolve, physicians and researchers will gain a better understanding of how an ATM gene mutation will guide medical care.  Because the information provided to patients will almost certainly change, those with an ATM gene mutation are encouraged to keep in touch with their medical providers in order to receive updates.

ATM testing in other family members

At this point in time, testing adult family members for a moderate risk gene mutation does NOT provide the same clarity or guidance that testing for a high risk gene mutation does. This is because moderate risk gene mutations should not be assumed to be the sole explanation for a particular family’s history of cancer.  For example, a family could have additional undetected/ unknown genetic and/or non-genetic risk factors contributing to the development of cancer seen in family members.  It is recommended that concerned family members discuss the issue of testing with their physicians.  If an adult family member were to test positive for the familial ATM gene mutation, increased cancer screening might be considered.  However, given the current lack of data regarding ATM gene mutations, if an adult family member were to test negative for a familial ATM gene mutation, that individual may still be at increased risk for cancer depending upon the family history and possibility for other genes to be playing a role in that individual/ family.  Cancer screening should be performed in accordance with the family history until further data is available.

Because of the potential risk for children to be affected with AT if both of their parents have ATM gene mutations, family members who are considering having children should speak with a genetic counselor to discuss risks and the possibility of having their partner tested before conceiving.

Significance of pathogenic or likely pathogenic change in ATM

When pathogenic (harmful) or likely pathogenic (likely harmful) changes (mutations) are detected in ATM, this information is informative in 4 ways:

  1. Diagnostics: It might have contributed to a cancer developing and provides part of an explanation as to why someone develops cancer.
  2. Prevention: If identified in other family members, early screening or risk reductive surgical planning might be indicated and pursued. Evidenced based counseling framework related literature.
  3. Therapeutics: The ATM gene produces a protein in the body essential for repair of cells and if this function is altered, a cell may be unstable and develop into a cancer. Specific medications are being studied as part of clinical trials for people with an inability to appropriately repair their DNA due to changes in ATM and other DNA damage related genes. Clinical Trials
  4. Family Planning: Some individuals and families may decide to use genetic information for planning a family.  It is important to know for ATM and other DNA damage genes in addition to a 50% risk for an offspring to also inherit a damaging change,  in the exceedingly rare circumstance  both parents carry a harmful change (mutation) in the same gene a rare and severe disease may occur in infancy or childhood with a probability of 25% for each pregnancy.

Variant of Uncertain Significance (VUSs) in the ATM gene

Not at this time. In order for a change in a gene to be determined as pathogenic or likely pathogenic significant evidence or burden of proof is needed given the importance of decisions and recommendations to be made.

Data Repositories for ATM Variants

The federal government is invested in learning more about variants of uncertain significance and tracking these variants in a central source called ClinVar.  However, significant expertise and curation is required before variants are deposited in this central source. PROMPT is dedicated to generating quality data.

The consequences of misclassification can be significant and costly when individuals make life impacting decisions.  Recently, the PROMPT study team illustrated in work spearheaded by Balamana et al. how different variants may be classified and the potential consequences of mis-classification based on the 4 main uses of this information by individuals and providers.

More information on the ATM gene:

  1. Gene Information:  OMIM, Orphanet, Decipher
  2. Where to send testing: GeneTests (where testing can be performed)
  3. Catalogue of mutations:  Locus Specific Database, ClinVar
  4. Registry information: Genetic Testing Registry


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