Abstract 3738: Associations between cigarette smoking and urinary estrogens/estrogen metabolites (EM) in premenopausal women
Authors: Fangyi Gu, Neil E. Caporaso, A Heather Eliassen, Xia Xu, Susan E. Hankinson, Regina G. Ziegler
Journal: Cancer Research (2011)

Abstract Smoking is a recognized risk factor for many cancers; however, its role in estrogen-related cancers is complex. Smoking has been hypothesized to increase breast cancer risk, although the evidence is mixed, and decrease endometrial cancer risk. Smoking is believed to reduce endogenous estrogen levels, which is suggested by earlier menopause and increased osteoporosis among smokers. However, the influence of smoking on estrogen metabolism is not known. We comprehensively examined the associations of creatinine-adjusted urinary concentrations of 15 estrogens/estrogen metabolites (EM) to cigarette smoking status and cigarettes per day (cpd) among 603 premenopausal women (428 never, 140 former, 35 current smokers) within the Nurses’ Health Study II. Data on smoking and other covariates were collected prospectively through biennial questionnaires; luteal phase urines collected during 1996-99 and questionnaire data from 1997 were used in this analysis. The 15 EM were quantified using a high-performance liquid chromatography-tandem mass spectrometry method with high sensitivity, specificity and reproducibility. EM were evaluated individually and grouped by metabolic pathway (2-, 4-, and 16-hydroxylation; catechols and methylated catechols). Absolute urinary concentrations, EM and EM groups as percent of total EM, and pathway ratios were analyzed. Age-adjusted geometric means of never, former and current smokers were calculated by generalized linear models (GLM). Tests for trend by cpd (0, 1-4, 5-14, 15+) were also generated by GLM after age-adjustment. Further analyses will examine reproductive, anthropometric, and other factors as potential confounders and possible explanations of observed associations. Current smokers had higher ratios of 2- to 16-pathway EM compared to never smokers (mean = 1.11 and 0.91, respectively), 4- to 16-pathway EM (mean = 0.12 and 0.08, respectively), and catechol to methylated catechol EM (mean = 7.2 and 5.9, respectively). Ratios were similar in former and never smokers. Urinary concentrations of total EM were not associated with cpd, but estradiol concentrations were inversely associated (p trend = 0.01). We observed positive trends between cpd and %2-pathway (p=0.05), %4-pathway (p=0.003), and %catechols (p=0.02); an inverse trend between cpd and %16-pathway (p=0.04); and no association between cpd and %parent estrogens or %methylated catechols. Similar, but less statistically significant, associations were observed for cpd and absolute concentrations of these pathways. These data provide a provocative initial evaluation of the associations among smoking, estrogen levels, and patterns of estrogen metabolism. In premenopausal women, current smoking status and smoking intensity are each significantly associated with estrogen metabolism profiles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3738. doi:10.1158/1538-7445.AM2011-3738