ATM-Related Cancer Risk
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 approximately a 2.5 to 3-fold increased risk of breast cancer as compared to the general population. The risk for a woman to develop contralateral breast cancer (i.e. a second cancer diagnosis, but in the opposite breast) in the setting of an ATM gene mutation is not yet defined, nor is the potential risk for new cancer diagnoses following exposure to radiation. ATM gene mutations have also been linked to an increased risk for pancreatic cancer and potentially prostate and ovarian cancer, but the lifetime risks for these types of cancer are not yet clearly 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
The best long-term medical management for individuals who carry a mutation in the ATM gene is a topic of on-going research. Healthcare providers oftentimes rely on an individual’s personal and family history to guide medical care.
- Breast: Depending upon personal and family history, in addition to standard clinical breast exams and mammography, some women may also consider increased breast cancer surveillance with breast MRI.
- Pancreas: 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.
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 unidentified genetic and/or non-genetic risk factors contributing to the development of cancer seen in family members. It is recommended that family members discuss the risks, benefits and limitations of genetic testing with their physician and/or genetic counselor. 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. 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. Genetic test results may be used by some individuals for reproductive decision-making including the use of pre-implantation genetic diagnosis (PGD), donor gametes, or adoption.
As research and data on cancer risk estimates continue to evolve, physicians and researchers will gain a better understanding of how an ATM gene mutation influences 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.
- Gatti R. Ataxia-Telangiectasia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle (WA)1993.
- Choi M, Kipps T, Kurzrock R. ATM Mutations in Cancer: Therapeutic Implications. Mol Cancer Ther. 2016;15(8):1781-91. doi: 10.1158/1535-7163.MCT-15-0945. PubMed PMID: 27413114.
- Tung N, Domchek SM, Stadler Z, Nathanson KL, Couch F, Garber JE, et al. Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016;13(9):581-8. doi: 10.1038/nrclinonc.2016.90. PubMed PMID: 27296296.
- Pritchard CC, Mateo J, Walsh MF, et al: Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med 375:443-53, 2016
- Salo-Mullen EE, O’Reilly EM, Kelsen DP, et al: Identification of germline genetic mutations in patients with pancreatic cancer. Cancer 121:4382-8, 2015
- Grant RC, Selander I, Connor AA, et al: Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer. Gastroenterology 148:556-64, 2015