Dietary iron intake and breast cancer risk: modulation by an antioxidant supplementation

Abstract

Experimental results suggested that iron-induced lipid peroxidation may explain the direct associations observed between red/processed meat intakes and colorectal and breast cancer risk. However, epidemiological evidence is lacking. Thus, we investigated the association between dietary iron intake and breast cancer risk, and its potential modulation by an antioxidant supplementation and lipid intake. This prospective study included 4646 women from the SU.VI.MAX trial (daily low-dose antioxidants vs. placebo). 188 incident breast cancers were diagnosed (median follow-up=12.6y). Dietary iron intake was assessed using repeated 24h dietary records. Multivariable Cox proportional hazards models were computed. Dietary iron intake was associated with an increased breast cancer risk (HRT3vs.T1=1.67 (1.02-2.71), P-trend=0.04). This association was observed in the placebo group (HRT3vs.T1=2.80 (1.42-5.54), P-trend=0.003), but not in the antioxidant-supplemented group (P-trend=0.7, P-interaction=0.1). Besides, in the placebo group, the increased breast cancer risk associated with dietary iron intake was more specifically observed in women with higher lipid intake (P-trend=0.046). These findings suggest that dietary iron intake may be associated with an increased breast cancer risk, especially in women who did not received antioxidants during the trial and who consumed more lipids. This supports the experimental results suggesting that breast cancer risk may be increased by iron-induced lipid peroxidation.

G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin

“…Population-based studies have taken a general approach to examine the relationship between iron and cancer risk. Although the results are not always consistent, the studies collectively support a model in which increased levels of iron in the body are associated with increased cancer risk 9 , 34 – 36 . Cancer cells always differ from their non-malignant counterparts in the levels or activity of many of the proteins that are involved in iron metabolism.…”

Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis

“…Among all 27 studies reviewed, the year of publication ranged from 1990 to 2018, with six studies published before 2000 [52–54, 67–69], nine studies between 2000 and 2009 [39, 55–61, 70], and 12 studies in 2010 or later [41, 42, 62–66, 71–75]. The majority of studies were conducted in the United States ( n = 12) [39, 42, 57, 58, 62–64, 66, 68–70, 73] or Canada ( n = 1) [59], while the rest were in Europe ( n = 9; including two in Germany and one in each of Denmark, Italy, the United Kingdom, Switzerland, France, Finland, and Sweden) [52–56, 65, 67, 72, 75], Asia ( n = 4; including two in China, one in Taiwan, and one in Japan) [41, 60, 61, 71], and Australia ( n = 1) [74].…”

Association between red and processed meat intake and colorectal adenoma incidence and recurrence: a systematic review and meta-analysis

“…Cooking red and processed meat is considered one of the major sources of carcinogens, such as heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), nitrate and N-nitroso compounds (NOCs), which are believed to play important roles in the etiology of cancer [ 37 – 39 ] and adenoma [ 35 , 40 ]. Second, a high iron intake from red meat may play a role in cancer [ 41 ] and CRA [ 42 ] by promoting the endogenous formation of carcinogenic N-nitroso compounds, causing oxidative damage and lipid peroxidation [ 43 ]. Third, positive associations have also been reported to be due to genetically controlled differences.…”