Abstract A22: Associations between dietary intake and novel genotoxic estrogen biomarkers implicated in breast cancer risk

Background: An expansive body of evidence implicates estrogen in the development of breast cancer (BC). Recently, a novel estrogen biomarker, the genotoxoic estrogen ratio (GER), was shown to be associated with BC. In addition, an elevated GER was observed in women at high-risk of BC, and furthermore, high GER has been shown to be reversible. Because of the potential for phytochemicals to inhibit activating enzymes and induce protective enzymes within the metabolism pathway resulting in reduced GER, we sought to examine associations between dietary factors and GER. Methods: This analysis was conducted in 53 pre-menopausal, healthy women aged 40-45 years from a cross-sectional study in which participants provided first-void urine samples and 3-day food records. The estrogen metabolites, conjugates and depurinating DNA adducts comprising the GER were identified from urine samples using ultraperformance liquid chromatography/ tandem mass spectrometry. The numerator of GER contains estrogen compounds which are bound to DNA as depurinating adducts, and thus have the potential to be genotoxic; the denominator contains the unbound estrogen counterparts consisting of estrogen metabolites and conjugates. A trend test was used to assess associations between tertiles of nutrient and food intake. Results: We observed GER to be associated with dietary intake after adjustment for age, total calories, percent adiposity, and estradiol. Specifically, elevated GER was associated with low vegetable intake (p=0.01), low carbohydrate consumption (p=0.01), low botanical intake (p=0.04), and high animal protein consumption (p=0.05). In particular, elevated GER was associated with the increasing servings of eggs (p=0.01) and fish (p=0.02) per day. In addition, low GER was associated with three botanical groupings: highest category of umbelliferae consumption (which includes carrots and celery; p=0.01), middle category of cruciferae consumption (which includes broccoli and cabbages; p=0.05), and middle category of ericaceae consumption (which includes blueberries and cranberries; p=0.05). Conclusion: These data provide the first investigation of lifestyle factors in relation to this novel GER biomarker. While these data would require replication, this early report suggesting inverse associations between dietary intake of botanical foods and GER provides an intriguing link between dietary factors and a novel biomarker with implications for breast cancer risk. Citation Format: Kerryn W. Reding, Muhammed Zahid, Ercole Cavalieri, Eleanor G. Rogan, Charlotte Atkinson, Mellissa Yong, Katherine Newton, Johanna Lampe. Associations between dietary intake and novel genotoxic estrogen biomarkers implicated in breast cancer risk. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A22.