Abstract 623: Iron intake, oxidative stress-related genes, and breast cancer risk
Authors: Chang Vicky C. , Cotterchio Michelle , Bondy Susan J. , Kotsopoulos Joanne 
Published: August 2019

Abstract
Background: Iron has been shown to enhance breast carcinogenesis in animal models through generation of oxidative stress, although epidemiological evidence of the association between iron intake and breast cancer risk remains inconclusive. This study investigated associations between different types of iron intake and breast cancer risk, and whether these associations were modified by genetic polymorphisms in antioxidant enzymes, including manganese superoxide dismutase (MnSOD) and glutathione S-transferases M1 (GSTM1) and T1 (GSTT1).
Methods: A population-based case-control study in Ontario, Canada recruited 3,030 breast cancer cases identified from the Ontario Cancer Registry and 3,402 controls from random digit dialing. Iron intake from foods and supplements was assessed using a 178-item food frequency questionnaire. Multivariable logistic regression analyses were used to evaluate associations between breast cancer risk and intakes of dietary, supplemental, and total (dietary plus supplemental) iron, among all women and stratified by menopausal status. Associations were also examined by hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)] tumor subtype. Among women providing saliva (DNA) samples (1,696 cases and 1,761 controls), interactions between iron intake and genetic polymorphisms were assessed using the likelihood ratio test.
Results: Among all women, intakes of dietary, supplemental, and total iron were not associated with breast cancer risk, overall or by tumor subtype. Among premenopausal women, there was an increase in breast cancer risk for the ER–PR– subtype associated with higher intakes (highest vs. lowest quintile) of dietary [odds ratio (OR) = 1.4; 95% confidence interval (CI): 0.9–2.4] and total (OR = 1.8; 95% CI: 1.1–2.9) iron (P for trend &lt; 0.05). Among postmenopausal women, supplemental iron intake (&gt;18 vs. 0 mg/day) was associated with reduced breast cancer risk (OR = 0.7; 95% CI: 0.5–0.9), with similar associations across tumor subtypes. Associations of dietary and total iron intake with overall breast cancer risk were modified by GSTT1 and/or GSTM1/T1 combined genotypes (P for interaction &lt; 0.05). For example, among women with deletions in both GSTM1 and GSTT1 loci, higher dietary iron intake was associated with increased breast cancer risk (OR = 2.1; 95% CI: 1.1–4.2), whereas null or inverse associations were found among women with other GSTM1/T1 genotypes.
Conclusions: Results from this study suggest that higher dietary and total iron intake may be associated with increased risk of ER–PR– breast cancer among premenopausal women, whereas higher supplemental iron intake may be associated with reduced postmenopausal breast cancer risk. In addition, associations between iron intake and breast cancer risk may be modified by polymorphisms in oxidative stress-related genes. Our ongoing work will investigate heme and non-heme iron intake in relation to breast cancer risk.
Citation Format: Vicky C. Chang, Michelle Cotterchio, Susan J. Bondy, Joanne Kotsopoulos. Iron intake, oxidative stress-related genes, and breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 623.