Several circulating carotenoids have been inversely associated with postmenopausal breast cancer risk in large cohort studies and a pooled analysis. Whether associations differ by tumor or participant characteristics remains unclear. We investigated the associations of plasma carotenoids with postmenopausal breast cancer risk overall and by estrogen receptor (ER) status, tumor stage, smoking status, and body mass index, in a case–control study nested in the Cancer Prevention Study II Nutrition Cohort.
A total of 496 invasive breast cancer cases diagnosed between blood draw in 1998–2001 and June 30, 2007 and matched 1:1 with controls on race, birth date, and blood draw date were included. Multivariable-adjusted conditional and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs).
Plasma α-carotene above the lowest quartile was associated with significant 40–43 % lower risk of invasive breast cancer risk (fourth vs. first quartile OR 0.60, 95 % CI 0.41–0.87, P-trend = 0.037) after adjustment for multiple covariates. This inverse association was strengthened after further adjustment for other plasma carotenoids and total fruit and vegetable intake (fourth vs. first quartile OR 0.50, 95 % CI 0.29–0.85, P-trend = 0.041). Other plasma carotenoids or total carotenoids were not associated with breast cancer risk. The inverse association of α-carotene with breast cancer remained for ER+, but not for ER− tumors, although test for heterogeneity was not statistically significant (P-heterogeneity = 0.49).
These results suggest that higher plasma α-carotene is associated with lower risk of invasive breast cancer.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Maiani G, Caston MJ, Catasta G et al (2009) Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Mol Nutr Food Res 53(Suppl 2):S194–S218
Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH (2007) Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Clin Chem 53:447–455
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49:1603–1616
Tang XH, Gudas LJ (2011) Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol 6:345–364
Hu F, Wang Yi B, Zhang W et al (2012) Carotenoids and breast cancer risk: a meta-analysis and meta-regression. Breast Cancer Res Treat 131:239–253
Zhang X, Spiegelman D, Baglietto L et al (2012) Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies. Am J Clin Nutr 95:713–725
Aune D, Chan DS, Vieira AR et al (2012) Fruits, vegetables and breast cancer risk: a systematic review and meta-analysis of prospective studies. Breast Cancer Res Treat 134:479–493
Jung S, Spiegelman D, Baglietto L et al (2013) Fruit and vegetable intake and risk of breast cancer by hormone receptor status. J Natl Cancer Inst 105:219–236
Aune D, Chan DS, Vieira AR et al (2012) Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 96:356–373
Eliassen AH, Hendrickson SJ, Brinton LA et al (2012) Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst 104:1905–1916
Wallstrom P, Wirfalt E, Lahmann PH, Gullberg B, Janzon L, Berglund G (2001) Serum concentrations of beta-carotene and alpha-tocopherol are associated with diet, smoking, and general and central adiposity. Am J Clin Nutr 73:777–785
Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC (1988) The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels. Am J Epidemiol 127:283–296
Calle EE, Rodriguez C, Jacobs EJ et al (2002) The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics. Cancer 94:2490–2501
El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H (2002) Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. Am J Clin Nutr 76:172–179
Holden JM, Eldridge AL, Beecher GR et al (1999) Carotenoid content of US foods: an update of the database. J Food Compos Anal 12:169–196
Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27
Wang M, Kuchiba A, Ogino S (2015) A meta-regression method for studying etiologic heterogeneity across disease subtypes classified by multiple biomarkers. Am J Epidemiol (in press)
Kleinbaum DG, Kupper LL, Muller KE (2007) Applied regression analysis and other multivariable methods. Cengage Learning, Belmont
Dorgan JF, Sowell A, Swanson CA et al (1998) Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 9:89–97
Hulten K, Van Kappel AL, Winkvist A et al (2001) Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden. Cancer Causes Control 12:529–537
Toniolo P, Van Kappel AL, Akhmedkhanov A et al (2001) Serum carotenoids and breast cancer. Am J Epidemiol 153:1142–1147
Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW (2002) Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 11:451–457
Tamimi RM, Hankinson SE, Campos H et al (2005) Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol 161:153–160
Sesso HD, Buring JE, Zhang SM, Norkus EP, Gaziano JM (2005) Dietary and plasma lycopene and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1074–1081
Dorjgochoo T, Gao YT, Chow WH et al (2009) Plasma carotenoids, tocopherols, retinol and breast cancer risk: results from the Shanghai Women Health Study (SWHS). Breast Cancer Res Treat 117:381–389
Epplein M, Shvetsov YB, Wilkens LR et al (2009) Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case–control study. Breast Cancer Res 11:R49
Kabat GC, Kim M, Adams-Campbell LL et al (2009) Longitudinal study of serum carotenoid, retinol, and tocopherol concentrations in relation to breast cancer risk among postmenopausal women. Am J Clin Nutr 90:162–169
Maillard V, Kuriki K, Lefebvre B et al (2010) Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in the E3N-EPIC study. Int J Cancer 127:1188–1196
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728
Gaudet MM, Gapstur SM, Sun J, Diver WR, Hannan LM, Thun MJ (2013) Active smoking and breast cancer risk: original cohort data and meta-analysis. J Natl Cancer Inst 105:515–525
Marangon K, Herbeth B, Lecomte E et al (1998) Diet, antioxidant status, and smoking habits in French men. Am J Clin Nutr 67:231–239
Ross MA, Crosley LK, Brown KM et al (1995) Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males: influences of smoking. Eur J Clin Nutr 49:861–865
Albanes D, Virtamo J, Taylor PR, Rautalahti M, Pietinen P, Heinonen OP (1997) Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 66:366–372
Heinonen OP, Albanes D (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The alpha-tocopherol, beta carotene cancer prevention study group. N Engl J Med 330:1029–1035
Omenn GS, Goodman GE, Thornquist MD et al (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155
Pradhan AD, Manson JE, Rossouw JE et al (2002) Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative observational study. JAMA 288:980–987
The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study II (CPS-II) cohort. We thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. We also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program.
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Wang, Y., Gapstur, S.M., Gaudet, M.M. et al. Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Causes Control 26, 1233–1244 (2015). https://doi.org/10.1007/s10552-015-0614-4
- Plasma carotenoids
- Breast cancer
- Estrogen receptor
- Cohort study
- Body mass index