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Background
Carotenoids and vitamin C are thought to be associated with reduced cancer risk due to their anti-oxidative capacity. We evaluated the associations of plasma carotenoid, tocopherol and vitamin C levels and risk of incident breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Methods
We used a nested case control design, and selected 1,502 female breast cancer cases with an oversampling of premenopausal and oestrogen receptor negative cases. Controls (n=1502) were time-matched to cases using an incidence density sampling design.
They were further matched on study centre, menopausal status, use of exogenous hormones, age, fasting status at blood collection, time of blood collection and phase of menstrual cycle. Baseline plasma samples were analysed for the carotenes: alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, cryptoxanthin and tocopherols: vitamin A, alpha-tocopherol and gamma-tocopherol by isocratic reserved phase high performance liquid chromatography (HPLC) and for plasma vitamin C by a colorimetric assay.
Conditional logistic regression was used to compute odds ratios for breast cancer risk. In these models we adjusted, in addition to the matching factors, for BMI, height, age at menarche, age at first full term pregnancy, ever use of pill, ever use of hormone therapy, smoking status, intake of alcohol, total energy, and saturated fatty acids, educational level and season of blood collection. The median follow-up time was nearly eight years.
Results
Risk of breast cancer was 27–34% lower for women in the highest quintile compared with that for women in the lowest quintile for plasma levels of Vitamin C (OR=0.66; 95% CI=0.49-0.90, p-trend=0.01), alpha-carotene (OR=0.72; 95% CI=0.52-0.99, p-trend=0.08), beta-carotene (OR=0.73; 95%=0.53-1.00, p-trend=0.11) and cryptoxanthin (OR=0.70; 95% CI=0.51-0.96, p-trend=0.21). Plasma vitamin C levels were similarly associated with all breast cancer subtypes, defined by menopausal status at diagnosis or estrogen receptor status. This was also the case for crytpoxanthin.
For alpha-carotene and beta-carotene the effects appeared somewhat stronger for post- than for premenopausal breast cancer. Their effects were stronger for, and largely restricted to, ER negative breast cancer (alpha-carotene, highest quintile (Q5) versus lowest quintile (Q1), OR=0.55; 95% CI=0.32-0.97, p-trend=0.02 and beta-carotene, Q5 versus Q1, OR=0.49; 95% CI=0.29-0.83, p-trend=0.02).
For most plasma antioxidants effects did not differ for current, past or never smokers or for women who consume more than 7, 1–7 or less than 1 glass of alcohol per week. The protective effect of vitamin C, however, was larger in never or past smokers than in current smokers (p interaction=0.04).
Conclusions
In this study we observed an inverse association of plasma vitamin C and some carotenoids with breast cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). The effect of carotenoids on ER- breast cancer was stronger than that on ER+ breast cancer. This difference was not seen for vitamin C. The effect of vitamin C was stronger in never and past smokers than in current smokers. Tocopherols were not related to breast cancer risk.