Plasma carotenoids, vitamin C and risk of breast cancer

Carla H Van Gils's research found that women with higher levels of vitamin C, alpha-carotene, beta-carotene or cryptoxanthin appeared to have a lower breast cancer risk than women with low levels of these antioxidants

  • Topic: Breast cancer
  • Institution: University Medical Centre Utrecht (UMCU)
  • Country: Netherlands
  • Status: Completed

Scientific abstract

(View plain language abstract)

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.

Plain language abstract

Background

Vegetables and fruits contain many putatively cancer protective substances. Several studies have used dietary questionnaires to measure vegetable and fruit consumption in large healthy populations and then followed participants for the occurrence of cancer. They do not show that vegetable and fruit consumption protects against breast cancer. It is, however, difficult to capture dietary habits by questionnaire and small protective effects may have been missed.

Carotenoids and vitamin C have cancer protective capacities and are abundantly present in vegetables and fruits. Blood levels of these micronutrients are good measures of vegetable and fruit consumption and they better estimate the concentration actually available to cells than dietary questionnaires.

Methods

We studied blood levels of carotenoids and vitamin C in relation to subsequent breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. At enrolment, blood samples, demographic, lifestyle and dietary data have been collected for participants from 10 European countries. Carotenoid and vitamin C levels were compared between 1,500 women who subsequently developed breast cancer and 1,500 healthy women.

Results

Women with higher levels of vitamin C, alpha-carotene, beta-carotene or cryptoxanthin appeared to have a lower breast cancer risk than women with low levels of these antioxidants. This was represented by an approximate 30% lower risk for those in the highest fifth of the antioxidant level distribution compared to those in the lowest fifth. The effects of carotenoids were stronger for oestrogen-receptor negative than for oestrogen-receptor positive breast cancer. The effects of vitamin C were stronger in never and past smokers than in current smokers.

Grant publications