Dallal, Cher M3; Stone, Roslyn A3; Cauley, Jane A3; Ness, Roberta B3; Vogel, Victor G3; Fentiman, Ian S3; Fowke, Jay H3; Krogh, Vittorio3; Loft, Steffen4; Meilahn, Elaine N3; Muti, Paola3; Olsen, Anja3; Overvad, Kim3; Sieri, Sabina3; Tjønneland, Anne3; Ursin, Giske3; Wellejus, Anja3; Taioli, Emanuela3
1 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet2 Section of Occupational and Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Public Health, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet
a combined analysis of individual level data
Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.¿Results: Higher premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). ¿Conclusions: Premenopausal urinary 2:16a-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16a-OHE1 overall, although obesity may modify associations with 2-OHE1.
International Journal of Biological Markers, 2013, Vol 28, Issue 1, p. 3-16