Journal article

Publication year: 2021

Pages: 89-96

Journal: Cancer Epidemiology, Biomarkers & Prevention

Volume number: 30

Issue number: 1

ISSN: 1055-9965

eISSN: 1538-7755

Open access status: Green

DOI Link: https://doi.org/10.1158/1055-9965.EPI-20-0471

Publisher: American Association for Cancer Research

Abstract: 

Background: No study has comprehensively examined how the steroid metabolome is associated with breast cancer risk in women with familial risk.

Methods: We examined 36 steroid metabolites across the spectrum of familial risk (5-year risk ranged from 0.14% to 23.8%) in pre- and postmenopausal women participating in the New York site of the Breast Cancer Family Registry (BCFR). We conducted a nested case-control study with 62 cases/124 controls individually matched on menopausal status, age, and race. We measured metabolites using GC-MS in urine samples collected at baseline before the onset of prospectively ascertained cases. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) per doubling in hormone levels.

Results: The average proportion of total steroid metabolites in the study sample were glucocorticoids (61%), androgens (26%), progestogens (11%), and estrogens (2%). A doubling in glucocorticoids (aOR = 2.7; 95% CI = 1.3-5.3) and androgens (aOR = 1.6; 95% CI = 1.0-2.7) was associated with increased breast cancer risk Specific glucocorticoids (THE, THF alpha THF, 6 beta-OH-F, THA, and alpha-THB) were associated with 49% to 161% increased risk Two androgen metabolites (AN and 11-OH-AN) were associated with 70% (aOR = 1.7; 95% CI = 1.1-2.7) and 90% (aOR = 1.9; 95% CI = 1.2-3.1) increased risk, respectively. One intermediate metabolite of a cortisol precursor (THS) was associated with 65% (OR = 1.65; 95% CI = 1.0-2.7) increased risk E1 and E2 estrogens were associated with 20% and 27% decreased risk, respectively.

Conclusions: Results suggest that glucocorticoids and 11-oxygenated androgens are positively associated with breast cancer risk across the familial risk spectrum.

Impact: if replicated, our findings suggest great potential of including steroids into existing breast cancer risk assessment tools.

Harvard Citation style: Houghton, L., Howland, R., Wei, Y., Ma, X., Kehm, R., Chung, W., et al. (2021) The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids, Cancer Epidemiology, Biomarkers & Prevention, 30(1), pp. 89-96. https://doi.org/10.1158/1055-9965.EPI-20-0471

APA Citation style: Houghton, L., Howland, R., Wei, Y., Ma, X., Kehm, R., Chung, W., Genkinger, J., Santella, R., Hartmann, M., Wudy, S., & Terry, M. (2021). The Steroid Metabolome and Breast Cancer Risk in Women with a Family History of Breast Cancer: The Novel Role of Adrenal Androgens and Glucocorticoids. Cancer Epidemiology, Biomarkers & Prevention. 30(1), 89-96. https://doi.org/10.1158/1055-9965.EPI-20-0471