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Int J Radiat Biol. 2018 Feb;94(2):97-105. doi: 10.1080/09553002.2018.1419303. Epub 2018 Jan 16.

Bioavailable serum estradiol may alter radiation risk of postmenopausal breast cancer: a nested case-control study.

Author information

1
a Radiation Effects Research Foundation , Hiroshima , Japan.
2
b Department of Statistics , Radiation Effects Research Foundation , Hiroshima , Japan.
3
c Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Epidemiology Branch, Basic Sciences Program , Bethesda , MD , USA.
4
d Translational Research Division , Research Center for Genomic Medicine, Saitama Medical University , Saitama , Japan.
5
e Department of Community Medicine , University of Connecticut Health Center , Farmington, CT , USA.
6
f Center for Data Science Education and Research, Shiga University , Hikone , Japan.
7
g Department of Statistics, College of Natural Science , Kyungpook National University , Daegu , South Korea.
8
h Division of Cancer Epidemiology and Genetics , NCI/NIH , Bethesda , MD , USA.
9
i Department of Clinical Studies , Radiation Effects Research Foundation , Hiroshima , Japan.
10
j Department of Molecular Biosciences , Radiation Effects Research Foundation , Hiroshima , Japan.

Abstract

PURPOSE:

Ionizing radiation and high levels of circulating estradiol are known breast cancer carcinogens. We investigated the risk of first primary postmenopausal breast cancer in relation to the combined effects of whole-body ionizing radiation exposure and prediagnostic levels of postmenopausal sex hormones, particularly bioavailable estradiol (bE2).

MATERIALS AND METHODS:

A nested case-control study of 57 incident breast cancer cases matched with 110 controls among atomic bomb survivors. Joint effects of breast radiation dose and circulating levels of sex hormones were assessed using binary regression and path analysis.

RESULTS AND CONCLUSION:

Radiation exposure, higher levels of bE2, testosterone and progesterone, and established reproductive risk factors were positively associated with postmenopausal breast cancer risk. A test for mediation of the effect of radiation via bE2 level suggested a small (14%) but significant mediation (p = 0.004). The estimated interaction between radiation and bE2 was large but not significant (interaction = 3.86; p = 0.32). There is accumulating evidence that ionizing radiation not only damages DNA but also alters other organ systems. While caution is needed, some portion of the radiation risk of postmenopausal breast cancer appeared to be mediated through bE2 levels, which may be evidence for cancer risks due to both direct and indirect effects of radiation.

KEYWORDS:

Breast cancer; estradiol; hormones; interaction; mediation; postmenopausal; radiation

PMID:
29307255
PMCID:
PMC6135639
DOI:
10.1080/09553002.2018.1419303
[Indexed for MEDLINE]
Free PMC Article

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