Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case–control study
To examine the association of plasma carotenoids, micronutrients in fruits, and vegetables, with risk of premalignant breast disease (PBD) in younger women.
Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month follow-up and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids.
The risk reduction between the highest and lowest tertiles varied by carotenoid, with β-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62–1.09; P trend = 0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48–1.44; P trend = 0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI ≥ 30 kg/m2; 61 cases and 115 controls) but not lean women (BMI < 25 kg/m2; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and β-carotene and higher levels of β-cryptoxanthin and lutein/zeaxanthin.
We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women, consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development.
KeywordsCarotenoids Benign breast disease Breast cancer African American Prevention
LY and GAC secured funding, conceived, and designed the study. KC and LY conducted statistical analyses with input from JL. KC wrote the first draft of the manuscript, which was critically revised by LY and GAC. All authors read and approved the final manuscript.
The study was supported by the Breast Cancer Research Foundation and the Siteman Investment Program at the Alvin J. Siteman Cancer Center in Washington University School of Medicine, St. Louis, Missouri. We thank the Siteman Biostatistics Shared Resource, which is supported in part by NCI Cancer Center Support Grant P30CA091842, for assistance in data analysis. We also thank Jeremy Furtado and his team for the carotenoid assays at the Nutritional Biomarker Laboratory within the Harvard T.H. Chan School of Public Health.
Compliance with ethical standards
Conflict of interest
Kevin Conhen, Ying Liu, Jingqin Luo, and Graham A. Colditz have no conflict of interest. Catherine M. Appleton has a consultant/advisory role in Hologic and Siemens.
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in this study based on the protocol approved by the Institutional Review Board at the Washington University in St. Louis.
- 2.Maiani G, Caston MJ, Catasta G, Toti E, Cambrodon IG, Bysted A, Granado-Lorencio F, Olmedilla-Alonso B, Knuthsen P, Valoti M, Bohm V, Mayer-Miebach E, Behsnilian D, Schlemmer U (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–S218CrossRefPubMedGoogle Scholar
- 4.Eliassen AH, Hendrickson SJ, Brinton LA, Buring JE, Campos H, Dai Q, Dorgan JF, Franke AA, Gao YT, Goodman MT, Hallmans G, Helzlsouer KJ, Hoffman-Bolton J, Hulten K, Sesso HD, Sowell AL, Tamimi RM, Toniolo P, Wilkens LR, Winkvist A, Zeleniuch-Jacquotte A, Zheng W, Hankinson SE (2012) Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst 104:1905–1916CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Epplein M, Shvetsov YB, Wilkens LR, Franke AA, Cooney RV, Le Marchand L, Henderson BE, Kolonel LN, Goodman MT (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:R49CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N, Stephenson HE Jr (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 9:89–97CrossRefPubMedGoogle Scholar
- 23.Wu C, Ray RM, Lin MG, Gao DL, Horner NK, Nelson ZC, Lampe JW, Hu YW, Shannon J, Stalsberg H, Li W, Fitzgibbons D, Porter P, Patterson RE, Satia JA, Thomas DB (2004) A case–control study of risk factors for fibrocystic breast conditions: Shanghai Nutrition and Breast Disease Study, China, 1995–2000. Am J Epidemiol 160:945–960CrossRefPubMedGoogle Scholar
- 33.Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, Travier N, Olsen A, Tjonneland A, Overvad K, Rinaldi S, Romieu I, Brennan P, Boutron-Ruault MC, Perquier F, Cadeau C, Boeing H, Aleksandrova K, Kaaks R, Kuhn T, Trichopoulou A, Lagiou P, Trichopoulos D, Vineis P, Krogh V, Panico S, Masala G, Tumino R, Weiderpass E, Skeie G, Lund E, Quiros JR, Ardanaz E, Navarro C, Amiano P, Sanchez MJ, Buckland G, Ericson U, Sonestedt E, Johansson M, Sund M, Travis RC, Key TJ, Khaw KT, Wareham N, Riboli E, van Gils CH (2016) Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr 103:454–464CrossRefPubMedGoogle Scholar
- 41.Kotsopoulos J, Tworoger SS, Campos H, Chung FL, Clevenger CV, Franke AA, Mantzoros CS, Ricchiuti V, Willett WC, Hankinson SE, Eliassen AH (2010) Reproducibility of plasma and urine biomarkers among premenopausal and postmenopausal women from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 19:938–946CrossRefPubMedPubMedCentralGoogle Scholar