Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies

Abstract

Background: Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies.

Methods: We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided.

Results: Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, P(trend) = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, P(trend) = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, P(trend) = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, P(trend) = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, P(trend) = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, β-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, P(trend) = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, P(trend) = .06; P(heterogeneity) = .01).

Conclusions: This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.

Figure 1.

Original (O) and recalibrated (R) medians of plasma or serum levels of carotenoids by study, among control subjects. *To convert μg/dL to μmol/L, multiply by the following factors: 0.01863 for α-carotene, β-carotene, and lycopene; 0.01810 for β-cryptoxanthin; 0.01758 for lutein+zeaxanthin. MEC = Multiethnic Cohort Study; NHS = Nurses’ Health Study; NYUWHS = New York University Women’s Health Study; SWHS = Shanghai Women’s Health Study; WHS = Women’s Health Study.

Figure 2.

Relative risks (RRs) of breast cancer and 95% confidence intervals (CIs) according to quintile of plasma carotenoids (μg/dL), recalibrated data. Diamonds represent relative risks; lines represent 95% confidence intervals. To convert μg/dL to μmol/L, multiply by the following factors: 0.01863 for α-carotene, β-carotene, and lycopene; 0.01810 for β-cryptoxanthin; 0.01758 for lutein+zeaxanthin. ref = referent.

Figure 3.

Relative risks (RRs) of breast cancer and 95% confidence intervals (CIs) according to quintile of plasma carotenoids, recalibrated data, by tumor estrogen receptor (ER) status. Diamonds represent relative risks; lines represent 95% confidence intervals. ER⁺ = estrogen receptor positive; ER⁻ = estrogen receptor negative; ref = referent.