Skip to main content

21-03-2010 | Oncology | Article

ATM gene mutations plus radiation may increase contralateral breast cancer risk


Free abstract

MedWire News: Certain rare mutations in the ataxia telangiectasia mutated (ATM) gene, when combined with radiation exposure, may increase a woman's risk for developing contralateral breast cancer, according to a study published in the Journal of the National Cancer Institute.

Jonine Bernstein (Memorial Sloan-Kettering Cancer Center, New York, USA) and colleagues explain that the ATM gene regulates cellular responses to the DNA damage induced by ionizing radiation, an established breast carcinogen.

However, it is unclear whether individuals who carry ATM mutations and are exposed to radiation are especially susceptible to radiation-induced breast cancer.

To investigate, Bernstein and team compared ATM mutations among women who had developed a second cancer in the contralateral breast (n=708) to mutations in a matched control group of women with unilateral breast cancer (n=1397).

All women underwent full mutation screening of the entire ATM gene. For those who had received radiation therapy, the researchers estimated the amount of radiation to the contralateral breast using treatment records and radiation measurements.

The researchers found that women who carried a rare ATM missense variant that was predicted to be deleterious and who also received radiation had a significant 2.8- to 3.3-fold higher risk for contralateral breast cancer, compared with women who did not have these mutations and had not had radiation. The risk for contralateral breast cancer increased with increasing radiation dose.

Women with both a mutation and radiation exposure also had a 5.3- to 5.8-fold higher risk for contralateral cancer than women who had a mutation but no radiation exposure.

Bernstein et al note that the missense variants were found in less than 1% of study participants, which implies that ATM mutations would account for only a small portion of second primary breast cancers observed in the population.

In an accompanying editorial, David Brenner, of Columbia University Medical Center in New York, notes that “the [study] results reemphasize that we do not yet understand most of the etiology of the disturbingly high long-term risks of second breast cancers. It is important, therefore, to continue to seek prophylactic preventative options that are useful for all breast cancer survivors."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Laura Dean

Related topics