Iron intake, oxidative stress‐related genes and breast cancer risk. Issue 5 (25th February 2020)

• Record Type: Journal Article
• Authors: Chang, Vicky C.; Cotterchio, Michelle; Bondy, Susan J.; Kotsopoulos, Joanne
• Is Part Of: International journal of cancer. Volume 147:Issue 5(2020)
• Page Start: 1354
• Page End: 1373
• Publication Date: 2020-02-25
• Subjects: iron intake -- heme iron -- breast cancer -- oxidative stress -- genetic polymorphisms; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32906
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress‐related genetic polymorphisms ( MnSOD, GSTM1 and GSTT1 ). A population‐based case–control study (3, 030 cases and 3, 402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1, 696 cases and 1, 761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all p trend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs . 0 mg/day = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (ORhighest vs . lowest quintile = 1.69, 95% CI: 1.16–2.47; p trend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions ( p interaction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity. Abstract : What's new? Iron may increase breast cancer risk through oxidative stress. Epidemiological evidence remains inconclusive, however, with few studies considering differences by type of iron, menopausal/hormone receptor status, and genetic variability. Results from this large population‐based case–control study do not support associations of iron intake with overall breast cancer risk; however, statistically significant associations were observed by menopausal and hormone receptor status. Higher intakes of total and nonheme iron in premenopausal women, and heme iron in postmenopausal women, increased risk of estrogen/progesterone receptor‐negative breast cancer. Furthermore, women with genotypes resulting in reduced antioxidant capacity may be more susceptible to high iron intake effects.