Associations of ionizing radiation and breast cancer-related serum hormone and growth factor levels in cancer-free female A-bomb survivors

Abstract

Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N = 412, ages 26-79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1 Gy of radiation dose among samples collected from postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%, respectively), while they decreased in samples collected from premenopausal women (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively). Interactions by menopausal status were significant (P = 0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there was a significant interaction by menopausal status (P = 0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.

FIG. 1

Log total estradiol (E₂) by menopausal status and radiation dose. The relative change is the percentage change at a dose of 1 Gy. The regression lines and P values are based on the final models obtained for the markers (Table 3). The slopes of the two regression lines by menopausal status are significantly different (P = 0.003).

FIG. 2

Log bioavailable estradiol (E₂) concentration by menopausal status and radiation dose. The relative change is the percentage change at a dose of 1 Gy. The regression lines and P values are based on the final models obtained for the markers (Table 3). The slopes of the two regression lines by menopausal status are significantly different (P < 0.001).

FIG. 3

Log testosterone by menopausal status and radiation dose. The relative change is the percentage change at a dose of 1 Gy. The regression lines and P values are based on the final models obtained for the markers (Table 3). The slopes of the two regression lines by menopausal status are significantly different (P < 0.001).

FIG. 4

IGF-1 by menopausal status and radiation dose. The relative change is the percentage change at a dose of 1 Gy. The regression lines and P values are based on the final models obtained for the markers (Table 3). The slopes of the two regression lines by menopausal status are significantly different (P = 0.014).