Premenopausal Plasma Ferritin Levels, HFE Polymorphisms, and Risk of Breast Cancer in the Nurses' Health Study II

Background: Evidence from the Nurses' Health Study II (NHSII) suggests that red meat consumption is associated with increased breast cancer risk in premenopausal women. Iron may be responsible by contributing to oxidative stress or effects on immune function.

Methods: We conducted a case-control study nested within the NHSII, examining prediagnostic plasma ferritin (n = 795 cases, 795 controls), 15 hemochromatosis gene (HFE) single-nucleotide polymorphisms (SNP; n = 765 cases, 1,368 controls), and breast cancer risk. Cases were diagnosed after providing blood samples between 1996 and 1999. ORs and 95% confidence intervals (CI) were calculated for ferritin levels by conditional logistic regression and for HFE SNPs by unconditional logistic regression.

Results: We did not observe a significant association between ferritin levels and breast cancer (top vs. bottom quartile multivariate OR: 1.05; 95% CI, 0.77-1.45; PTrend = 0.77). Results did not change when restricted to women who were premenopausal at blood draw, and were similar when cases were examined by hormone receptor status, and menopausal status at diagnosis. No HFE SNPs were significantly associated with breast cancer in a log-additive manner. Among controls, ferritin levels were nominally associated with SNPs rs9366637 (PTrend = 0.04), rs6918586 (PTrend = 0.06), and rs13161 (PTrend = 0.07), but results did not remain significant after adjusting for multiple testing.

Conclusions: Ferritin levels and HFE SNPs were not associated with breast cancer risk in this population.

Impact: Components of red meat other than iron are likely responsible for its positive association with breast cancer in premenopausal women.