Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses’ health studies
High levels of circulating carotenoids are hypothesized to reduce breast cancer risk, potentially due to their antioxidant properties. However, little is known about the relationship between carotenoid exposure earlier in life and risk. We examined associations of premenopausal plasma carotenoids and markers of oxidative stress and risk of breast cancer among 1179 case–control pairs in the Nurses’ Health Study (NHS) and NHSII. Levels of α- and β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin were quantified by high-performance liquid chromatography. Three fluorescent oxidation products (FlOP_360, FlOP_320, FlOP_400) were measured in a subset of participants by spectrofluoroscopy. Multivariate conditional logistic regression was used to estimate odds ratios and 95 % confidence intervals for breast cancer by quartile, as well as P values for tests of linear trend. We additionally examined whether 45 single-nucleotide polymorphisms (SNPs) in five genes involved in oxidative and antioxidative processes or carotenoid availability were associated with risk. Carotenoid measures were not inversely associated with breast cancer risk. No differences by estrogen receptor status were observed, though some inverse associations were observed among women postmenopausal at diagnosis. Plasma FlOP levels were not positively associated with risk, and suggestive inverse associations with FlOP_320 and FlOP_360 were observed. Several SNPs were associated with carotenoid levels, and a small number were suggestively associated with breast cancer risk. We observed evidence of interactions between some SNPs and carotenoid levels on risk. We did not observe consistent associations between circulating levels of premenopausal carotenoids or FlOP levels and breast cancer risk.
KeywordsBreast cancer Fluorescent oxidation products Carotenoids Oxidative stress
We would like to thank the participants and staff of the Nurses Health Study and NHSII for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data.
Conflict of interest
This study was supported in part by R01 CA050385 (Walter Willett, PI) and UM1 CA176726 (Willett, PI). This project was additionally supported in part by UM1 CA186107, P01 CA87969, R01 CA49449, and R01 CA67262. Julia Sisti was supported by training Grants R25 CA098566 and T32 CA900137.
- 11.Sato R et al (2002) Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomark Prev 11:451–457Google Scholar
- 24.Eliassen AH et al (2014) Plasma carotenoids and risk of breast cancer over 20 years of follow-up. Am J Clin Nutr 74:2919Google Scholar
- 26.Wu T, Rifai N, Roberts LJ 2nd, Willett WC, Rimm EB (2004) Stability of measurements of biomarkers of oxidative stress in blood over 36 h. Cancer Epidemiol Biomark Prev 13:1399–1402Google Scholar
- 36.Frei B (1994) Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med 97, 5S–13S; discussion 22S–28SGoogle Scholar