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Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women

  • Sahoko Takagi (a1), Mariko Naito (a1), Sayo Kawai (a1), Rieko Okada (a1), Chisato Nagata (a2), Satoyo Hosono (a3), Yuichiro Nishida (a4), Naoyuki Takashima (a5), Sadao Suzuki (a6), Ippei Shimoshikiryo (a7), Haruo Mikami (a8), Hirokazu Uemura (a9), Nagato Kuriyama (a10), Keizo Ohnaka (a11), Michiaki Kubo (a12), Nobuyuki Hamajima (a13), Hideo Tanaka (a3) (a14) and Kenji Wakai (a1)...


Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47–69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2–Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.


Corresponding author

* Corresponding author: S. Takagi, fax +81 52 744 2971, email


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1. Torre, LA, Siegel, RL, Ward, EM, et al. (2016) Global cancer incidence and mortality rates and trends – an update. Cancer Epidemiol Biomarkers Prev 25, 1627.
2. Katanoda, K, Matsuda, T, Matsuda, A, et al. (2013) An updated report of the trends in cancer incidence and mortality in Japan. Jpn J Clin Oncol 43, 492507.
3. Key, T, Appleby, P, Barnes, I, et al. (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94, 606616.
4. Missmer, SA, Eliassen, AH, Barbieri, RL, et al. (2004) Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst 96, 18561865.
5. Gruber, CJ, Tschugguel, W, Schneeberger, C, et al. (2002) Production and actions of estrogens. N Engl J Med 346, 340352.
6. Al-Azzawi, F & Palacios, S (2009) Hormonal changes during menopause. Maturitas 63, 135137.
7. World Cancer Research Fund & American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity, and Prevention of Cancer: A Global Perspective. Washington, DC: AICR.
8. Brinkman, MT, Baglietto, L, Krishnan, K, et al. (2010) Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations. Eur J Clin Nutr 64, 176183.
9. Holmes, MD, Spiegelman, D, Willett, WC, et al. (2000) Dietary fat intake and endogenous sex steroid hormone levels in postmenopausal women. J Clin Oncol 18, 36683676.
10. Wu, AH, Pike, MC & Stram, DO (1999) Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast cancer. J Natl Cancer Inst 91, 529534.
11. Olson, SH, Bandera, E V & Orlow, I (2007) Variants in estrogen biosynthesis genes, sex steroid hormone levels, and endometrial cancer: a HuGE review. Am J Epidemiol 165, 235245.
12. Hosono, S, Ito, H, Oze, I, et al. (2015) Polymorphisms in CYP19A1, HSD17B1 and HSD17B2 genes and serum sex hormone level among postmenopausal Japanese women. Maturitas 82, 394401.
13. Kidokoro, K, Ino, K, Hirose, K, et al. (2009) Association between CYP19A1 polymorphisms and sex hormones in postmenopausal Japanese women. J Hum Genet 54, 7885.
14. Shi, L, Yang, X, Dong, X, et al. (2016) Polymorphism of HSD17B1 Ser312Gly with cancer risk: evidence from 66,147 Subjects. Twin Res Hum Genet 19, 136145.
15. Feigelson, HS, Cox, DG, Cann, HM, et al. (2006) Haplotype analysis of the HSD17B1 gene and risk of breast cancer: a comprehensive approach to multicenter analyses of prospective cohort studies. Cancer Res 66, 24682475.
16. Nagata, C, Nagao, Y, Shibuya, C, et al. (2005) Fat intake is associated with serum estrogen and androgen concentrations in postmenopausal Japanese women. J Nutr 135, 28622865.
17. Hamajima, N (2007) The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene-environment interactions for cancer. Asian Pac J Cancer Prev 8, 317323.
18. Wakai, K, Hamajima, N, Okada, R, et al. (2011) Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: a project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. J Epidemiol 21, 223235.
19. Tokudome, S, Goto, C, Imaeda, N, et al. (2004) Development of a data-based short food frequency questionnaire for assessing nutrient intake by middle-aged Japanese. Asian Pac J Cancer Prev 5, 4043.
20. Tokudome, Y, Goto, C, Imaeda, N, et al. (2005) Relative validity of a short food frequency questionnaire for assessing nutrient intake versus three-day weighed diet records in middle-aged Japanese. J Epidemiol 15, 135145.
21. Imaeda, N, Goto, C, Tokudome, Y, et al. (2007) Reproducibility of a short food frequency questionnaire for Japanese general population. J Epidemiol 17, 100107.
22. Resources Council, Science and Technology Agency, Japan (2000) Standard Tables of Food Composition in Japan, 5th ed. Tokyo: Resources Council, Science and Technology Agency, Japan (in Japanese).
23. Wakai, K, Tamakoshi, K, Date, C, et al. (2005) Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan. Cancer Sci 96, 590599.
24. Kuriki, K, Hirose, K, Wakai, K, et al. (2007) Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese. Int J Cancer 121, 377385.
25. Zheng, J-S, Hu, X-J, Zhao, Y-M, et al. (2013) Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ 346, f3706.
26. Ohnishi, Y, Tanaka, T, Ozaki, K, et al. (2001) A high-throughput SNP typing system for genome-wide association studies. J Hum Genet 46, 471477.
27. Dallal, CM, Tice, JA, Buist, DSM, et al. (2014) Estrogen metabolism and breast cancer risk among postmenopausal women: a case-cohort study within B~FIT. Carcinogenesis 35, 346355.
28. Falk, RT, Brinton, LA, Dorgan, JF, et al. (2013) Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study. Breast Cancer Res 15, R34.
29. Fuhrman, BJ, Schairer, C, Gail, MH, et al. (2012) Estrogen metabolism and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 104, 326339.
30. Key, TJ, Appleby, PN, Reeves, GK, et al. (2015) Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: reanalysis of eighteen prospective studies. Steroids 99, 4955.
31. Nagata, C, Nagao, Y, Yamamoto, S, et al. (2008) Light exposure at night, urinary 6-sulfatoxymelatonin, and serum estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiol Biomarkers Prev 17, 14181423.
32. Campbell, KL, Foster-Schubert, KE, Alfano, CM, et al. (2012) Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal women: randomized controlled trial. J Clin Oncol 30, 23142326.
33. van Gemert, WAM, Schuit, AJ, van der Palen, J, et al. (2015) Effect of weight loss, with or without exercise, on body composition and sex hormones in postmenopausal women: the SHAPE-2 trial. Breast Cancer Res 17, 120.
34. Murtaugh, MA, Herrick, J, Sweeney, C, et al. (2011) Macronutrient composition influence on breast cancer risk in Hispanic and non-Hispanic white women: the 4-Corners Breast Cancer Study. Nutr Cancer 63, 185195.
35. Lajous, M, Boutron-Ruault, M-C, Fabre, A, et al. (2008) Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women. Am J Clin Nutr 87, 13841391.
36. Sugawara, N, Yasui-Furukori, N, Umeda, T, et al. (2015) Relationship between dietary patterns and cognitive function in a community-dwelling population in Japan. Asia Pac J Public Health 27, NP2651NP2660.
37. Wu, AH, Stanczyk, FZ, Seow, A, et al. (2002) Soy intake and other lifestyle determinants of serum estrogen levels among postmenopausal Chinese women in Singapore. Cancer Epidemiol Biomarkers Prev 11, 844851.
38. Smith-Warner, SA, Spiegelman, D, Adami, HO, et al. (2001) Types of dietary fat and breast cancer: a pooled analysis of cohort studies. Int J Cancer 92, 767774.
39. Tokudome, Y, Imaeda, N, Ikeda, M, et al. (1999) Foods contributing to absolute intake and variance in intake of fat, fatty acids and cholesterol in middle-aged Japanese. J Epidemiol 9, 7890.
40. Kuriki, K, Nagaya, T, Tokudome, Y, et al. (2003) Plasma concentrations of (n-3) highly unsaturated fatty acids are good biomarkers of relative dietary fatty acid intakes: a cross-sectional study. J Nutr 133, 36433650.
41. Goto, C, Tokudome, Y, Imaeda, N, et al. (2006) Validation study of fatty acid consumption assessed with a short food frequency questionnaire against plasma concentration in middle-aged Japanese people. Food Nutr Res 50, 7782.
42. Young, LR, Kurzer, MS, Thomas, W, et al. (2011) Effect of dietary fat and omega-3 fatty acids on urinary eicosanoids and sex hormone concentrations in postmenopausal women: a randomized controlled feeding trial. Nutr Cancer 63, 930939.
43. Larsson, SC, Kumlin, M, Ingelman-Sundberg, M, et al. (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79, 935945.
44. Richards, JA & Brueggemeier, RW (2003) Prostaglandin E2 regulates aromatase activity and expression in human adipose stromal cells via two distinct receptor subtypes. J Clin Endocrinol Metab 88, 28102816.
45. Puranen, TJ, Poutanen, MH, Peltoketo, HE, et al. (1994) Site-directed mutagenesis of the putative active site of human 17 beta-hydroxysteroid dehydrogenase type 1. Biochem J 304, 289293.
46. The National Center for Biotechnology Information (2016) Cluster Report: rs605059. (accessed July 2016).
47. Wu, AH, Seow, A, Arakawa, K, et al. (2003) HSD17B1 and CYP17 polymorphisms and breast cancer risk among Chinese women in Singapore. Int J Cancer 104, 450457.
48. Iwasaki, M, Hamada, GS, Nishimoto, IN, et al. (2010) Dietary isoflavone intake, polymorphisms in the CYP17, CYP19, 17beta-HSD1, and SHBG genes, and risk of breast cancer in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians. Nutr Cancer 62, 466475.
49. Setiawan, VW, Hankinson, SE, Colditz, GA, et al. (2004) HSD17B1 gene polymorphisms and risk of endometrial and breast cancer. Cancer Epidemiol Biomarkers Prev 13, 213219.
50. Yao, L, Cao, L-H, Qiu, L-X, et al. (2010) The association between HSD17B1 Ser312Gly polymorphism and breast cancer risk: a meta-analysis including 31,053 subjects. Breast Cancer Res Treat 123, 577580.
51. Date, C, Fukui, M, Yamamoto, A, et al. (2005) Reproducibility and validity of a self-administered food frequency questionnaire used in the JACC study. J. Epidemiol 15, Suppl. 1, S9S23.
52. Tsugane, S, Kobayashi, M, Sasaki, S, et al. (2003) Validity of the self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I: comparison with dietary records for main nutrients. J Epidemiol 13, S51S56.
53. Karim, R, Stanczyk, FZ, Brinton, RD, et al. (2015) Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. J Clin Endocrinol Metab 100, 508515.
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