Abstract 1883: Dietary nitrate and nitrite, micronutrients, and postmenopausal breast cancer risk in the NIH-AARP Diet and Health Study
Authors: Inoue-Choi Maki , Sinha Rashmi , Gierach Gretchen L. , Ward Mary H. 
Published: August 2015

Abstract
Background: Ingested nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOCs), potential human carcinogens. Vitamin C inhibits and heme iron enhances NOC formation. To date, interactions between dietary nitrate and nitrite intakes and these micronutrients have not been evaluated in relation to the risk for breast cancer in prospective cohort studies.
Methods: We followed 191,926 postmenopausal women in the NIH-AARP Diet and Health Study for incident breast cancer. Dietary intake was assessed using a food frequency questionnaire at baseline (1995). Daily nitrate and nitrite intakes were computed for total, animal, and processed meat sources, and adjusted for energy intake using a density method. We computed multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by quintiles of nitrate and nitrite for all breast cancers, by estrogen/progesterone receptor (ER/PR) status, and by stage (localized, regional/distant) using Cox proportional hazards regression. We stratified analyses by low or high (≤ or &gt; median) heme iron (138 mg/1,000kcal) and total vitamin C (273 mg/d) intakes.
Results: We identified 7,508 incident invasive breast cancers (1995-2006). On average, 95% of nitrate and 70% of nitrite intakes were from plant sources. Red processed meat intake was not associated with risk of all breast cancer but was positively associated with risk of localized breast cancer (adjusted HR = 1.35 for Q5, CI = 1.11-1.42, p-trend&lt;0.001). Heme iron intake was positively associated with risk of all breast cancer (HR = 1.12 for Q5, CI = 1.04-1.21, p-trend = 0.004). Total nitrate intake was associated with higher risk of all breast cancer, particularly among women with high heme iron intake (HR = 1.15, CI = 1.01-1.30 for Q5, p-trend = 0.02), but not among women with low heme iron intake (p-trend = 0.63, p-interaction = 0.17); similar associations were observed when evaluating total nitrate intake in relation to hormone receptor positive cancers (p-interaction = 0.09 for total nitrate x heme iron in relation to ER+/PR+ positive cancer). Total nitrite intake was not associated with overall breast cancer risk. Nitrite intake from processed red meats was associated with higher risk of localized (HR = 1.23, 95%CI = 1.09-1.39 for Q5, p-trend&lt;0.001) but not regional/distant breast cancers (p-trend = 0.41). Vitamin C intake did not interact with nitrate or nitrite intake in relation to breast cancer risk.
Conclusions: Our findings suggest that high nitrate intake and nitrite intake from processed meats may increase postmenopausal women's risk of breast cancer, especially for those with high heme iron intake.
Citation Format: Maki Inoue-Choi, Rashmi Sinha, Gretchen L. Gierach, Mary H. Ward. Dietary nitrate and nitrite, micronutrients, and postmenopausal breast cancer risk in the NIH-AARP Diet and Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1883. doi:10.1158/1538-7445.AM2015-1883