Abstract 4296: Serum estrogen and estrogen metabolites and smoking among postmenopausal women in the Women's Health Initiative Observational Study
Authors: Yang Hannah P. , Anderson Garnet , Behan Sally , Brinton Louise A. , Chen Chu , Falk Roni , Oh Hannah , Pfeiffer Ruth , Tindle Hilary , Wentzensen Nicolas , Trabert Britton 
Published: July 2016

Abstract
BACKGROUND: A consistent inverse relation between smoking and endometrial cancer risk has been observed, with a meta-analysis demonstrating that smokers are at a 29% (95% confidence interval: 0.65-0.78) lower risk than non-smokers among postmenopausal women. Although smoking may have different effects on other hormone-related cancers, it has been proposed that smoking shifts estrogen metabolism to favor hydroxylation of estrone and estradiol along the 2 as compared with 4 or 16 pathways, thereby presumably reducing estrogenic activity. However, comprehensive studies examining the interrelationships between smoking and estrogen production and metabolism are limited, especially among postmenopausal women.
METHODS: Within the Women's Health Initiative Observational Study, a cohort of 93,676 postmenopausal women recruited between 1993 and 1998, 15 estrogens/estrogen metabolites (jointly referred to as EM) were measured by liquid chromatography/tandem mass spectrometry in pre-diagnostic serum among 974 women (all never/former menopausal hormone therapy users) for a nested case-control study of ovarian and endometrial cancers. Using inverse probability weighted linear regression, we calculated geometric means (GM; pmol/L) of individual EM, adjusted for age at and year of blood draw, time since menopause, race, and body mass index (BMI), by smoking status (never, former, current), intensity (1 pack/day; &lt;5, 5-&lt;20, 20+ pack/years), and duration (&lt;10, 10-19, 20-29, 30+ years). Percent difference was calculated by the difference over the mean EM values across categories of smoking factors. Statistical heterogeneity across categories of smoking factors was assessed using the Wald chi-square test.
RESULTS: Overall, we observed slightly lower, although non-significant EM levels among current compared to never smokers (GM for current vs. never smokers were 331 vs. 352 for estrone, 56.3 vs. 58.8 for estradiol; p-value&gt;0.83), with an indication that this association was limited to women with BMI 25+ kg/m2. We observed similar associations after excluding women defined as cancer cases at time of blood draw. Furthermore, current compared to never smokers had non-significant lower levels in the 2- (GM were 160 vs. 163; percent diff = -2%) as compared with 4- (16.0 vs. 15.7; 2%) or 16- (259 vs. 256; 1%) hydroxylation pathways (p-value&gt;0.82). Among smokers, EM levels tended to increase across categories of packs/day, but we observed no consistent patterns for years of smoking and pack/years.
CONCLUSIONS: Our finding that circulating EM are highest in non-smokers is at odds with the increases in EM seen with smoking intensity among smokers. This suggests that smoking may not be altering estrogen production and metabolism as hypothesized and smoking may be inversely associated with endometrial cancer via other non-hormonal pathways.
Citation Format: Hannah P. Yang, Garnet Anderson, Sally Behan, Louise A. Brinton, Chu Chen, Roni Falk, Hannah Oh, Ruth Pfeiffer, Hilary Tindle, Nicolas Wentzensen, Britton Trabert. Serum estrogen and estrogen metabolites and smoking among postmenopausal women in the Women's Health Initiative Observational Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4296.