The Association between Circulating Carotenoids and Risk of Breast Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies

Abstract

Carotenoids appear to have anticancer effects. Prospective evidence for the relation between serum carotenoids and breast cancer is controversial. The present systematic review and meta-analysis aimed to investigate the link between circulating carotenoids and the risk of breast cancer. We performed a systematic search of PubMed, Scopus, and Web of Science up to 30 November, 2022. Prospective studies on adults aged >/=18 y that have reported risk estimates for the association between circulating carotenoids and breast cancer risk were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for combining studies' risk estimates. Dose-response relations were explored through a 1-stage random-effects model. Fifteen publications (17 nested case-control studies and 1 cohort study) with 20,188 participants and 7608 cases were included. We observed an inverse association between the highest level of circulating total carotenoids (relative risk RR: 0.76; 95% confidence interval CI: 0.62, 0.93; n = 8), alpha-carotene (RR: 0.77; 95% CI: 0.68, 0.87; n = 13), beta-carotene (RR: 0.80; 95% CI: 0.65, 0.98; n = 15), beta-cryptoxanthin (RR: 0.85; 95% CI: 0.74, 0.96; n = 11), lycopene (RR: 0.86; 95% CI: 0.76, 0.98; n = 13), and lutein (RR: 0.70; 95% CI: 0.52, 0.93; n = 6) and the risk of breast cancer compared with the lowest level. Additionally, each 10 mug/dL of total carotenoids, alpha-carotene, beta-carotene, and beta-cryptoxanthin was associated with 2%, 22%, 4%, and 10% lower risk of breast cancer, respectively. This relationship was stronger at lower levels of total carotenoids and beta-cryptoxanthin. The certainty of evidence was rated from very low to low. Most studies were performed among Western nations, which should be acknowledged for extrapolation of findings. Total circulating carotenoids, alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein seem to be related to a decreased risk of breast cancer. Our findings could have practical importance for public health. This study was registered at PROSPERO as CRD42023434983.