Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer

Background: High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Materials and Methods: Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. Results: We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (p < 0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (${\beta}=-0.463$, p = 0.002) but unrelated to age (${\beta}=-0.080$, p = 0.570) or obesity (${\beta}=-0.180$, p = 0.208). Conclusions: The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.