An example of gene-environment interaction: mammography screening and radiation-induced breast cancer among women with a familial or genetic predisposition

M.C. Jansen-van der Weide1, M.J.W. Greuter, M. Oudkerk, G.H. de Bock
Department of Radiology, University Medical Center Groningen1

Background: Women at increased risk of breast cancer, participating in a screening program, are exposed to radiation. Although these women are exposed to low radiation doses (1.5-3 mSv), ionizing radiation, depending on dose and age at exposure, becomes more hazardous, when received at younger age, and for a longer period. Furthermore, the presence of a mutation in the DDRP genes could precipitate the harmful effect of radiation. We conducted a literature search on epidemiological studies, describing effects of low-dose radiation on breast cancer risk of women with a familial or genetic predisposition.

Materials and Methods: We conducted a systematic search in Pubmed and EMBASE. The search strategy ´Breast neoplasms AND Mass screening OR Mammography OR neoplasms, radiation-induced" was combined with text words focusing on high-risk women.

Preliminary results: Of the 34 articles found, 7 studies were selected. Four studies examined the effect of exposure to low-dose radiation among mutation carriers (Andrieu, Goldfrank, Narod, Bernstein). The other three studies researched the effect of radiation among women with and without a family history of breast cancer (Hill, John, Broeks).
The studies among carriers, which showed an effect of radiation (n=3), primarily found an increased breast cancer risk for women exposed at young ages and for a higher number of exposures. The studies among women with and without a positive family history all showed an effect of exposure to radiation on breast cancer risk. Two studies revealed a greater breast cancer risk among high-risk women (family history, OR: 1.8, 95% CI: 1.0-3.1; genetic predisposition, OR: 2.2, 95% CI: 1.0-4.6).

Conclusions: Taken into account study design, study power, and type of comparison, it is likely that low-dose radiation increases breast cancer risk among young women. Current results suggest an increased breast cancer risk due to mammography screening among women with a familial or genetic predisposition.