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Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case–control study

  • Epidemiology
  • Published:
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Abstract

Purpose

To examine the association of plasma carotenoids, micronutrients in fruits, and vegetables, with risk of premalignant breast disease (PBD) in younger women.

Methods

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.

Results

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.

Conclusions

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.

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References

  1. Kreiter E, Richardson A, Potter J, Yasui Y (2014) Breast cancer: trends in international incidence in men and women. Br J Cancer 110:1891–1897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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–S218

    Article  PubMed  Google Scholar 

  3. Dorjgochoo T, Gao YT, Chow WH, Shu XO, Li H, Yang G, Cai Q, Rothman N, Cai H, Franke AA, Zheng W, Dai Q (2009) Plasma carotenoids, tocopherols, retinol and breast cancer risk: results from the Shanghai Women Health Study (SWHS). Breast Cancer Res Treat 117:381–389

    Article  CAS  PubMed  Google 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 104:1905–1916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tamimi RM, Hankinson SE, Campos H, Spiegelman D, Zhang S, Colditz GA, Willett WC, Hunter DJ (2005) Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol 161:153–160

    Article  PubMed  Google 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:R49

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wang Y, Gapstur SM, Gaudet MM, Furtado JD, Campos H, McCullough ML (2015) Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort. Cancer Causes Control 26:1233–1244

    Article  CAS  PubMed  Google Scholar 

  8. Eliassen AH, Liao X, Rosner B, Tamimi RM, Tworoger SS, Hankinson SE (2015) Plasma carotenoids and risk of breast cancer over 20 years of follow-up. Am J Clin Nutr 101:1197–1205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pouchieu C, Galan P, Ducros V, Latino-Martel P, Hercberg S, Touvier M (2014) Plasma carotenoids and retinol and overall and breast cancer risk: a nested case–control study. Nutr Cancer 66:980–988

    Article  CAS  PubMed  Google Scholar 

  10. Aune D, Chan DS, Vieira AR, Navarro Rosenblatt DA, Vieira R, Greenwood DC, Norat T (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

    Article  CAS  PubMed  Google Scholar 

  11. Yan B, Lu MS, Wang L, Mo XF, Luo WP, Du YF, Zhang CX (2016) Specific serum carotenoids are inversely associated with breast cancer risk among Chinese women: a case–control study. Br J Nutr 115:129–137

    Article  CAS  PubMed  Google Scholar 

  12. Sisti JS, Lindstrom S, Kraft P, Tamimi RM, Rosner BA, Wu T, Willett WC, Eliassen AH (2015) Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses’ health studies. Breast Cancer Res Treat 151:415–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Brinton LA, Sherman ME, Carreon JD, Anderson WF (2008) Recent trends in breast cancer among younger women in the United States. J Natl Cancer Inst 100:1643–1648

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yeum KJ, Ahn SH, Rupp de Paiva SA, Lee-Kim YC, Krinsky NI, Russell RM (1998) Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer. J Nutr 128:1920–1926

    CAS  PubMed  Google Scholar 

  15. Wellings SR, Jensen HM, Marcum RG (1975) An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst 55:231–273

    CAS  PubMed  Google Scholar 

  16. Boeke CE, Tamimi RM, Berkey CS, Colditz GA, Eliassen AH, Malspeis S, Willett WC, Frazier AL (2014) Adolescent carotenoid intake and benign breast disease. Pediatrics 133:e1292–e1298

    Article  PubMed  PubMed Central  Google Scholar 

  17. Shavers VL, Harlan LC, Stevens JL (2003) Racial/ethnic variation in clinical presentation, treatment, and survival among breast cancer patients under age 35. Cancer 97:134–147

    Article  PubMed  Google Scholar 

  18. 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

    CAS  PubMed  Google Scholar 

  19. Dupont WD, Page DL (1985) Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312:146–151

    Article  CAS  PubMed  Google 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 9:89–97

    Article  CAS  PubMed  Google Scholar 

  21. Toniolo P, Van Kappel AL, Akhmedkhanov A, Ferrari P, Kato I, Shore RE, Riboli E (2001) Serum carotenoids and breast cancer. Am J Epidemiol 153:1142–1147

    Article  CAS  PubMed  Google Scholar 

  22. Nelson ZC, Ray RM, Wu C, Stalsberg H, Porter P, Lampe JW, Shannon J, Horner N, Li W, Wang W, Hu Y, Gao D, Thomas DB (2010) Fruit and vegetable intakes are associated with lower risk of breast fibroadenomas in Chinese women. J Nutr 140:1294–1301

    Article  CAS  PubMed  PubMed Central  Google 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 160:945–960

    Article  PubMed  Google Scholar 

  24. Hislop TG, Band PR, Deschamps M, Ng V, Coldman AJ, Worth AJ, Labo T (1990) Diet and histologic types of benign breast disease defined by subsequent risk of breast cancer. Am J Epidemiol 131:263–270

    Article  CAS  PubMed  Google Scholar 

  25. Ingram DM, Nottage E, Roberts T (1991) The role of diet in the development of breast cancer: a case–control study of patients with breast cancer, benign epithelial hyperplasia and fibrocystic disease of the breast. Br J Cancer 64:187–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Galvan-Portillo M, Torres-Sanchez L, Lopez-Carrillo L (2002) Dietary and reproductive factors associated with benign breast disease in Mexican women. Nutr Cancer 43:133–140

    Article  PubMed  Google Scholar 

  27. Rao AV, Rao LG (2007) Carotenoids and human health. Pharmacol Res 55:207–216

    Article  CAS  PubMed  Google Scholar 

  28. Steinmetz KA, Potter JD (1991) Vegetables, fruit, and cancer. II. Mechanisms. Cancer Causes Control 2:427–442

    Article  CAS  PubMed  Google Scholar 

  29. Hirsch K, Atzmon A, Danilenko M, Levy J, Sharoni Y (2007) Lycopene and other carotenoids inhibit estrogenic activity of 17beta-estradiol and genistein in cancer cells. Breast Cancer Res Treat 104:221–230

    Article  CAS  PubMed  Google Scholar 

  30. Simeone AM, Tari AM (2004) How retinoids regulate breast cancer cell proliferation and apoptosis. Cell Mol Life Sci 61:1475–1484

    Article  CAS  PubMed  Google Scholar 

  31. Tang XH, Gudas LJ (2011) Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol 6:345–364

    Article  CAS  PubMed  Google Scholar 

  32. Prakash P, Russell RM, Krinsky NI (2001) In vitro inhibition of proliferation of estrogen-dependent and estrogen-independent human breast cancer cells treated with carotenoids or retinoids. J Nutr 131:1574–1580

    CAS  PubMed  Google 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 103:454–464

    Article  CAS  PubMed  Google Scholar 

  34. Tamimi RM, Colditz GA, Wang Y, Collins LC, Hu R, Rosner B, Irie HY, Connolly JL, Schnitt SJ (2011) Expression of IGF1R in normal breast tissue and subsequent risk of breast cancer. Breast Cancer Res Treat 128:243–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schleicher RL, Sternberg MR, Pfeiffer CM (2013) Race-ethnicity is a strong correlate of circulating fat-soluble nutrient concentrations in a representative sample of the U.S. population. J Nutr 143:966S–976S

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Kant AK, Graubard BI (2007) Ethnicity is an independent correlate of biomarkers of micronutrient intake and status in American adults. J Nutr 137:2456–2463

    CAS  PubMed  Google Scholar 

  37. Arab L, Cambou MC, Craft N, Wesseling-Perry K, Jardack P, Ang A (2011) Racial differences in correlations between reported dietary intakes of carotenoids and their concentration biomarkers. Am J Clin Nutr 93:1102–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, Gitto E, Arrigo T (2015) Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 16:378–400

    Article  Google Scholar 

  39. Amengual J, Lobo GP, Golczak M, Li HN, Klimova T, Hoppel CL, Wyss A, Palczewski K, von Lintig J (2011) A mitochondrial enzyme degrades carotenoids and protects against oxidative stress. FASEB J 25:948–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. London SJ, Connolly JL, Schnitt SJ, Colditz GA (1992) A prospective study of benign breast disease and the risk of breast cancer. JAMA 267:941–944

    Article  CAS  PubMed  Google 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 19:938–946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liu Y, Colditz GA, Rosner B, Berkey CS, Collins LC, Schnitt SJ, Connolly JL, Chen WY, Willett WC, Tamimi RM (2013) Alcohol intake between menarche and first pregnancy: a prospective study of breast cancer risk. J Natl Cancer Inst 105:1571–1578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author’s contributions

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.

Funding

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.

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Correspondence to Graham A. Colditz.

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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.

Ethical approval

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

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.

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Cohen, K., Liu, Y., Luo, J. et al. Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case–control study. Breast Cancer Res Treat 162, 571–580 (2017). https://doi.org/10.1007/s10549-017-4152-5

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  • DOI: https://doi.org/10.1007/s10549-017-4152-5

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