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Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the nurses' health study II.

ABSTRACT: 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.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.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.Ferritin levels and HFE SNPs were not associated with breast cancer risk in this population.Components of red meat other than iron are likely responsible for its positive association with breast cancer in premenopausal women.

SUBMITTER: Graff RE

PROVIDER: S-EPMC3951649 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the nurses' health study II.

Graff Rebecca E RE Cho Eunyoung E Lindström Sara S Kraft Peter P Willett Walter C WC Eliassen A Heather AH

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20140117 3

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 24443403

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Project description:IntroductionPrior research supports an association between endogenous sex steroids and breast cancer among postmenopausal women; the association is less clear among premenopausal women.MethodsWe evaluated the associations between estrogens, androgens, progesterone and sex hormone binding globulin (SHBG) and breast cancer in a nested case-control study in the Nurses' Health Study II. Between 1996 and 1999, 29,611 participants provided blood samples; 18,521 provided samples timed in early follicular and mid-luteal phases of the menstrual cycle. A total of 634 women, premenopausal at blood collection, developed breast cancer between 1999 and 2009 and were matched to 1,264 controls (514 cases and 1,030 controls with timed samples). We used conditional logistic regression controlling for breast cancer risk factors for overall analyses; unconditional logistic regression additionally controlling for matching factors was used for subgroup analyses.ResultsIn analyses of premenopausal estrogens including breast cancers diagnosed both before and after menopause, there was no association between follicular estradiol, estrone and free estradiol and risk of either total or invasive breast cancer. Luteal estradiol was positively associated with estrogen receptor positive (ER+)/progesterone receptor positive (PR+) cancers (5th vs. 1st quintile odds ratio (OR): 1.7 (95% confidence interval (CI): 1.0 to 2.9), Ptrend = 0.02). Luteal estrone, free estradiol and progesterone were not associated with risk. Androgens were suggestively or significantly associated with risk when the sample was restricted to invasive tumors (for example, testosterone: OR: 1.4 (1.0 to 2.0), Ptrend = 0.23) and ER+/PR+ disease (testosterone: OR: 1.7 (1.1 to 2.6) Ptrend = 0.10; dehydroepiandrosterone sulfate (DHEAS) OR: 1.3 (0.8 to 2.0) Ptrend = 0.05). SHBG was not associated with breast cancer risk. The results varied by menopausal status at diagnosis, with follicular estradiol suggestively positively associated with breast cancers in women premenopausal at diagnosis (OR: 1.1 (0.9 to 1.3) and significantly inversely associated with postmenopausal disease (OR: 0.6 (0.4 to 0.9); Pheterogeneity < 0.01).ConclusionsAndrogens were associated with modestly increased risk of breast cancer in this population, with stronger associations for invasive and ER+/PR+ disease. Luteal phase estradiol levels were suggestively associated with ER+/PR+ tumors but no other strong associations were observed with estrogens. Associations with follicular phase estrogens may vary by menopausal status at diagnosis, but case numbers were limited. Additional studies to confirm the role of premenopausal hormones in the etiology of both premenopausal and postmenopausal breast cancer are needed.

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Dataset Information

Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the nurses' health study II.

Publications

Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the nurses' health study II.

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