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Circulating carotenoids, mammographic density, and subsequent risk of breast cancer.

ABSTRACT: Mammographic density is one of the strongest predictors of breast cancer risk. Recently, it has been suggested that reactive oxygen species may influence breast cancer risk through its influence on mammographic density. In the current study, we addressed this hypothesis and also assessed if the association between carotenoids and breast cancer risk varies by mammographic density. We conducted a nested case-control study consisting of 604 breast cancer cases and 626 controls with prospectively measured circulating carotenoid levels and mammographic density in the Nurses' Health Study. Circulating levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were measured. We used a computer-assisted thresholding method to measure percent mammographic density. We found no evidence that circulating carotenoids are inversely associated with mammographic density. However, mammographic density significantly modified the association between total circulating carotenoids and breast cancer (P heterogeneity = 0.008). Overall, circulating total carotenoids were inversely associated with breast cancer risk (P trend = 0.01). Among women in the highest tertile of mammographic density, total carotenoids were associated with a 50% reduction in breast cancer risk (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). In contrast, there was no inverse association between carotenoids and breast cancer risk among women with low mammographic density. Similarly, among women in the highest tertile of mammographic density, high levels of circulating alpha-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were associated with a significant 40% to 50% reduction in breast cancer risk (P trend < 0.05). Our results suggest that plasma levels of carotenoids may play a role in reducing breast cancer risk, particularly among women with high mammographic density.

SUBMITTER: Tamimi RM

PROVIDER: S-EPMC2820729 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Circulating carotenoids, mammographic density, and subsequent risk of breast cancer.

Tamimi Rulla M RM Colditz Graham A GA Hankinson Susan E SE

Cancer research 20091201 24

Mammographic density is one of the strongest predictors of breast cancer risk. Recently, it has been suggested that reactive oxygen species may influence breast cancer risk through its influence on mammographic density. In the current study, we addressed this hypothesis and also assessed if the association between carotenoids and breast cancer risk varies by mammographic density. We conducted a nested case-control study consisting of 604 breast cancer cases and 626 controls with prospectively me ...[more]

PMID: 19934322

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Project description:BackgroundHigher circulating carotenoids are associated with lower breast cancer risk. The underlying biology remains under-explored.MethodsWe profiled 293 prediagnostic plasma metabolites in a nested case-control study (n = 887 cases) within the Nurses' Health Studies. Associations between circulating carotenoids and metabolites were identified using linear-mixed models (FDR ≤ 0.05), and we further selected metabolites most predictive of carotenoids with LASSO. Metabolic signatures for carotenoids were calculated as weighted sums of LASSO selected metabolites. We further evaluated the metabolic signatures in relation to breast cancer risk using conditional logistic-regression.ResultsWe identified 48 to 110 metabolites associated with plasma levels of α-carotene, β-carotene, β-cryptoxanthin, estimated-vitamin-A-potential, lutein/zeaxanthin, and lycopene, which included primarily positively associated metabolites implicated in immune regulation (tryptophan), redox balance (plasmalogens, glutamine), epigenetic regulations (acetylated-/methylated-metabolites), and primarily inversely associated metabolites involved in β-oxidation (carnitines; FDR ≤ 0.05). The metabolomic signatures derived for β-carotene (Q4 vs. Q1 relative risk RR = 0.74, P trend = 0.02), and estimated-vitamin-A-potential (Q4 vs. Q1 RR = 0.74, P trend = 0.02)-measured ≥10 years before diagnosis-were associated with lower breast cancer risk. Modest attenuations of RR for measured levels of β-carotene and estimated-vitamin-A-potential were seen when we adjusted for their corresponding metabolic signatures.ConclusionsMetabolites involved in immune regulation, redox balance, membrane signaling, and β-oxidation were associated with plasma carotenoids. Although some metabolites may reflect shared common food sources or compartmental colocalization with carotenoids, others may signal the underlying pathways of carotenoids-associated lowered breast cancer risk.ImpactConsumption of carotenoid-rich diet is associated with a wide-range of metabolic changes which may help to reduce breast cancer risk.

Project description:Breast density and microcalcifications are strongly associated with the risk of breast cancer. However, few studies have evaluated the combined association between these two factors and breast cancer risk. We investigated the association between breast density, microcalcifications, and risk of breast cancer. This cohort study included 3,910,815 women aged 40-74 years who were screened for breast cancer between 2009 and 2010 and followed up until 2020. The National Health Insurance Service database includes national health-screening results from the national breast cancer screening program, which is an organized screening program provided every 2 years for all women aged 40 years or older. Breast density was assessed based on the Breast Imaging Reporting and Data System (BI-RADS) 4th edition, mostly through visual assessment by radiologists. The presence or absence of microcalcifications was obtained from the mammographic results. Cox proportional hazard regression for breast cancer risk was used to estimate hazard ratios (aHRs) adjusted for breast cancer risk factors. A total of 58,315 women developed breast cancer during a median follow-up of 10.8 years. Women with breast cancer had a higher proportion of microcalcifications than women without breast cancer (0.9% vs. 0.3%). After adjusting for breast density, women with microcalcification had a 3.07-fold (95% confidence interval [CI] 2.82-3.35) increased risk of breast cancer compared to women without microcalcification. The combined association between microcalcification and breast density dramatically increased the risk of breast cancer, corresponding to a higher level of breast density. Among postmenopausal women, the highest risk group was women with BI-RADS 4 and microcalcification. These women had more than a sevenfold higher risk than women with BI-RADS 1 and non-microcalcification (aHR, 7.26; 95% CI 5.01-10.53). Microcalcification is an independent risk factor for breast cancer, and its risk is elevated when combined with breast density.

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Circulating carotenoids, mammographic density, and subsequent risk of breast cancer.

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Circulating carotenoids, mammographic density, and subsequent risk of breast cancer.

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