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Plasma amino acid profiles are associated with biomarkers of breast cancer risk in premenopausal Japanese women

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Abstract

Objective

Recently, profiles of plasma amino acids have been utilized to detect diseases including breast cancer. However, there is a possibility that the amino acid status may be associated with the risk of breast cancer. We investigated the relationship of plasma levels of amino acids with levels of sex hormones and insulin-like growth factor (IGF)-1, which are relevant to the etiology of premenopausal breast cancer, in normal premenopausal women.

Methods

Participants were 350 Japanese women who had regular menstrual cycles less than 40-day long. Fasting plasma samples were assayed for estradiol, testosterone, dehydroepiandrosterone sulfate, sex-hormone-binding globulin (SHBG), and IGF-1. A total of 20 amino acids in plasma were quantified by liquid chromatography–mass spectrometry. Information on lifestyle and reproductive factors was obtained using a self-administered questionnaire.

Results

The plasma arginine level was significantly inversely correlated with plasma levels of total and free estradiol and IGF-1 after adjusting for age, body mass index, and phase of the menstrual cycle. Plasma leucine and tyrosine levels were significantly positively correlated with the free testosterone level. The ratio of plasma asparagine to the total amino acids was significantly positively correlated with SHBG level.

Conclusions

Plasma levels of some specific amino acids, such as arginine, leucine, tyrosine, and asparagine, were associated with the levels of sex hormones, SHBG, or IGF-1 in premenopausal women. However, the present cross-sectional study cannot provide a cause–effect relation. The implication of amino acids in the etiology of breast cancer needs to be addressed in future studies.

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References

  1. Chadeau-Hyam M, Ebbels TM, Brown IJ et al (2010) Metabolic profiling and the metabolome-wide association study: significance level for biomarker identification. J Proteome Res 9:4620–4627

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Becker S, Kortz L, Helmschrodt C, Thiery J, Ceglarek U (2012) LC–MS-based metabolomics in the clinical laboratory. J Chromatogr B 883–884:68–75

    Article  Google Scholar 

  3. Nakamura T, Takebe K, Rudoh K et al (1994) Increased plasma gluconeogenic and system A amino acids in patients with pancreatic diabetes due to chronic pancreatitis in comparison with primary diabetes. Tohoku J Exp Med 173:413–420

    Article  CAS  PubMed  Google Scholar 

  4. Chen Y, Zhang R, Song Y, He J et al (2009) RRLC–MS/MS-based metabonomics combined with in-depth analysis of metabolic correlation network: finding potential biomarkers for breast cancer. Analyst 134:2003–2011

    Article  CAS  PubMed  Google Scholar 

  5. Kamaura M, Nishijima K, Takahashi M, Ando T, Mizushima S, Tochikubo O (2010) Lifestyle modification in metabolic syndrome and associated changes in plasma amino acid profiles. Circ J 74:2434–2440

    Article  CAS  PubMed  Google Scholar 

  6. Slupsky CM, Steed H, Wells TH et al (2010) Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin Cancer Res 16:5835–5841

    Article  CAS  PubMed  Google Scholar 

  7. Miyagi Y, Higashiyama M, Gochi A et al (2011) Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS ONE 6:e24143

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17

    Article  PubMed  Google Scholar 

  9. Marshall S (2006) Role of insulin, adipocyte hormones, and nutrient-sensing pathways I regulating fuel metabolism and energy homeostasis: a nutritional perspective of diabetes, obesity, and cancer. Sci STKE 346:re7

    Google Scholar 

  10. Kaaks R, Berrino F, Key T et al (2005) Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 97:755–765

    Article  CAS  PubMed  Google Scholar 

  11. Fortner RT, Eliassen AH, Spiegelman D, Willett WC, Barbieri RL, Hankinson SE (2013) Premenopausal endogenous steroid hormones and breast cancer risk: results from the Nurses’ Health Study II. Breast Cancer Res 15:R19. doi:10.1186/bcr3394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. The Endogenous Hormones and Breast Cancer Collaborative Group (2010) Insulin-like growth factor 1 (IGF1), IGF-binding protein 3 (IGFBP3), and breast cancer risk: reanalysis of 17 prospective studies. Lancet Oncol 11:530–542

    Article  PubMed Central  Google Scholar 

  13. Møller SE, Møller-Maach B, Olsen M, Fjalland B (1996) Effects of oral contraceptives on plasma neutral amino acids and cholesterol during a menstrual cycle. Eur J Clin Pharmacol 50:179–184

    Article  PubMed  Google Scholar 

  14. Ferrando AA, Tipton KD, Doyle D, Phillips SM, Cortiella J, Wolfe RR (1998) Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol 275:E864–E871

    CAS  PubMed  Google Scholar 

  15. Hamadeh MJ, Devries MC, Tarnopolsky MA (2005) Estrogen supplementation reduces whole body leucine and carbohydrate oxidation and increases lipid oxidation in men during endurance exercise. J Clin Endocrinol Metab 90:3592–3599

    Article  CAS  PubMed  Google Scholar 

  16. Nagata C, Nakamura K, Oba S, Hayashi M, Takeda N, Yasuda K (2009) Association of intakes of fat, dietary fiber, soy isoflavone, and alcohol with uterine fibroids in Japanese women. Br J Nutr 101:1427–1431

    Article  CAS  PubMed  Google Scholar 

  17. Nagata C, Wada K, Nakamura K, Hayashi M, Takeda N, Yasuda K (2011) Associations of body size and reproductive factors with circulating levels of sex hormones and prolactin in premenopausal Japanese women. Cancer Cause Control 22:581–588

    Article  Google Scholar 

  18. Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1983) Calculation of free and bound fractions of testosterone and estradiol-17β to human plasma proteins at body temperature. J Steroid Biochem 16:801–810

    Article  Google Scholar 

  19. Tessari P, Cecchet D, Cosma A et al (2011) Insulin resistance of amino acid and protein metabolism in type 2 diabetes. Clin Nutr 30:267–272

    Article  CAS  PubMed  Google Scholar 

  20. Zhang SM, Willett WC, Selhub J et al (2003) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst 95:373–380

    Article  CAS  PubMed  Google Scholar 

  21. Lin J, Lee I-M, Song Y et al (2010) Plasma homocysteine and cysteine and risk of breast cancer in women. Cancer Res 70:2397–2405

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Zhang SM, Willett WC, Selhub J, Manson JE, Colditz GA, Hankinson SE (2003) A prospective study of plasma total cysteine and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12:1188–1193

    CAS  PubMed  Google Scholar 

  23. Teyssier C, Le Romancer M, Sentis S, Jalaquier S, Corbo L, Cavaillés V (2009) Protein arginine methylation in estrogen signaling and estrogen-related cancers. Trends Endocrinol Metab 21:181–189

    Article  PubMed  Google Scholar 

  24. Holden DP, Cartwright JE, Nussey SS, Whitley GSJ (2003) Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine. Circulation 108:1575–1580

    Article  CAS  PubMed  Google Scholar 

  25. Çevik D, Unay Ö, Durmusoglu F, Yurdun T, Bilsel AS (2006) Plasma markers of NO synthase activity in women after ovarian hyperstimulation: influence of estradiol on ADMA. Vasc Med 11:7–12

    Article  PubMed  Google Scholar 

  26. Verhoeven MO, Hemelaar M, Teerlink T, Kenemans P, Van der Mooren MJ (2007) Effects of intranasal versus oral hormone therapy on asymmetric dimethylarginine in healthy postmenopausal women: a randomized study. Atherosclerosis 195:181–188

    Article  CAS  PubMed  Google Scholar 

  27. Hamelers IH, Van Schaik RF, Sussenbach JS, Steenbergh PH (2003) 17 beta-estradiol responsiveness of MCF-7 laboratory strains is dependent on an autocrine signal activating the IGF type I receptor. Cancer Cell Int 3:10

    Article  PubMed Central  PubMed  Google Scholar 

  28. Urban RJ (2011) Growth hormone and testosterone: anabolic effects on muscle. Horm Res Paediatr 76(Suppl 1):81–83

    Article  CAS  PubMed  Google Scholar 

  29. Garlick PJ (2005) The role of leucine in the regulation of protein metabolism. J Nutr 135:1553S–1556S

    CAS  PubMed  Google Scholar 

  30. Tai ES, Tan MLS, Stevens RD et al (2010) Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia 53:757–767

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Batch BC, Shah SH, Newgard CB et al (2013) Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness. Metabolism. doi: 10.1016/j.metabol.2013.01.007

  32. Kelly DM, Jones HT (2013) Testosterone: a metabolic hormone in health and disease. J Endocrinol 217:R25–R45

    Article  CAS  PubMed  Google Scholar 

  33. Cory JG, Cory AH (2006) Critical roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: asparaginase treatment in childhood acute lymphoblastic leukemia. In vivo 20:587–590

    CAS  PubMed  Google Scholar 

  34. Stančáková A, Civelek M, Saleem NK et al (2012) Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men. Diabetes 61:1895–1902

    Article  PubMed  Google Scholar 

  35. Wallace IR, McKinley MC, Bell PM, Hunter SJ (2013) Sex hormone binding globulin and insulin resistance. Clin Endocrinol (Oxf) 78:321–329

    Article  CAS  Google Scholar 

  36. Verkasalo PK, Thomas HV, Appleby PN, Davey GK, Key TJ (2011) Circulating levels of sex hormones and their relations to risk factors for breast cancer: a cross-sectional study in 1,092 pre- and postmenopausal women (United Kingdom). Cancer Causes Control 12:47–59

    Article  Google Scholar 

  37. Bezemer ID, Rinaldi S, Dossus L et al (2005) C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control 16:561–572

    Article  PubMed  Google Scholar 

  38. Rinaldi S, Peeters PH, Bezemer ID et al (2006) Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition. Cancer Causes Control 17:1033–1043

    Article  CAS  PubMed  Google Scholar 

  39. Tsuji M, Tamai Y, Wada K et al (2012) Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women. Cancer Causes Control 23:683–689

    Article  PubMed  Google Scholar 

  40. Townsend MK, Clish CB, Kraft P et al (2013) Reproducibility of metabolomics profiles among men and women in 2 large cohort studies. Clin Chem. doi:10.1373/clinchem.2012.199133

    PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by Grants-in-Aid for Scientific Research on Innovative Areas (No. 221S0001) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan

    Chisato Nagata, Keiko Wada & Michiko Tsuji

  2. Department of Food and Nutrition, Japan Women’s University, Tokyo, Japan

    Michiko Tsuji

  3. Department of Internal Medicine, Matsunami General Hospital, Gifu, Japan

    Makoto Hayashi & Keigo Yasuda

  4. Department of Endocrinology and Metabolism, Murakami Memorial Hospital, Asahi University, Gifu, Japan

    Noriyuki Takeda

Authors
  1. Chisato Nagata
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  2. Keiko Wada
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  3. Michiko Tsuji
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  4. Makoto Hayashi
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  5. Noriyuki Takeda
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  6. Keigo Yasuda
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Correspondence to Chisato Nagata.

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Nagata, C., Wada, K., Tsuji, M. et al. Plasma amino acid profiles are associated with biomarkers of breast cancer risk in premenopausal Japanese women. Cancer Causes Control 25, 143–149 (2014). https://doi.org/10.1007/s10552-013-0316-8

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  • DOI: https://doi.org/10.1007/s10552-013-0316-8

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