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19.09.2017 | Original paper

Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women

verfasst von: Devon J. Boyne, Christine M. Friedenreich, John B. McIntyre, Frank Z. Stanczyk, Kerry S. Courneya, Will D. King

Erschienen in: Cancer Causes & Control | Ausgabe 12/2017

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Abstract

Purpose

Epigenetic mechanisms may help to explain the complex and heterogeneous relation between sex hormones and cancer. Few studies have investigated the effects of sex hormones on epigenetic markers related to cancer risk such as levels of methylation within repetitive DNA elements. Our objective was to describe the association between endogenous sex hormone exposure and levels of LINE-1 and Alu methylation in healthy postmenopausal women.

Methods

We nested a cross-sectional study within the Alberta Physical Activity and Breast Cancer Prevention Trial (2003–2006). Study participants consisted of healthy postmenopausal women who had never been diagnosed with cancer (n = 289). Sex hormone exposures included serum concentrations of estradiol, estrone, testosterone, androstenedione, and sex hormone-binding globulin. We estimated the participants’ lifetime number of menstrual cycles (LNMC) as a proxy for cumulative exposure to ovarian sex hormones. Buffy coat samples were assessed for DNA methylation. Linear regression was used to model the associations of interest and to control for confounding.

Results

Both estradiol and estrone had a significant positive dose–response association with LINE-1 methylation. LNMC was associated with both LINE-1 and Alu methylation. Specifically, LNMC had a non-linear “U-shaped” association with LINE-1 methylation regardless of folate intake and a negative linear association with Alu methylation, but only amongst low folate consumers. Androgen exposure was not associated with either outcome.

Conclusion

Current and cumulative estrogen exposure was associated with repetitive element DNA methylation in a group of healthy postmenopausal women. LINE-1 and Alu methylation may be epigenetic mechanisms through which estrogen exposure impacts cancer risk.

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Hancks DC, Kazazian HH (2016) Roles for retrotransposon insertions in human disease. Mob DNA 7:9. doi:10.1186/s13100-016-0065-9 CrossRefPubMedPubMedCentral

Padeken J, Zeller P, Gasser SM (2015) Repeat DNA in genome organization and stability. Curr Opin Genet Dev 31:12–19. doi:10.1016/j.gde.2015.03.009 CrossRefPubMed

Bernstein BE, Meissner A, Lander ES (2007) The mammalian epigenome. Cell 128:669–681. doi:10.1016/j.cell.2007.01.033 CrossRefPubMed

DeRoo LA, Bolick SC, Xu Z, Umbach DM, Shore D, Weinberg CR, Sandler DP, Taylor JA (2014) Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study. Carcinogenesis 35(2):333–338. doi:10.1093/carcin/bgt34 CrossRefPubMed

Joyce BT, Gao T, Zheng Y, Liu L, Zhang W, Dai Q, Shrubsole MJ, Hibler EA, Cristofanilli M, Zhang H, Yang H (2016). Prospective changes in global DNA methylation and cancer incidence and mortality. Br J Cancer 115(4):465–472. doi:10.1038/bjc.2016.205 CrossRefPubMedPubMedCentral

Muka T, Koromani F, Portilla E, O’Connor A, Bramer WM, Troup J, Chowdhury R, Dehghan A, Franco OH (2016) The role of epigenetic modifications in cardiovascular disease: a systematic review. Int J Cardiol 212:174–183. doi:10.1016/j.ijcard.2016.03.062 CrossRefPubMed

Jakovcevski M, Akbarian S (2012) Epigenetic mechanisms in neurological disease. Nat Med 18:1194–1204. doi:10.1038/nm.2828 CrossRefPubMedPubMedCentral

Brown SB, Hankinson SE (2014) Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Steroids 99:8–10. doi:10.1016/j.steroids.2014.12.013 CrossRefPubMed

Barzi A, Lenz AM, Labonte MJ, Lenz HJ (2013) Molecular pathways: estrogen pathway in colorectal cancer. Clin Cancer Res 19:5842–5848. doi:10.1158/1078-0432.CCR-13-0325 CrossRefPubMed

10.

Mendelsohn ME (2002) Protective effects of estrogen on the cardiovascular system. Am J Cardiol 89:12–17CrossRef

11.

Arevalo M-A, Azcoitia I, Garcia-Segura LM (2015) The neuroprotective actions of oestradiol and oestrogen receptors. Nat Rev Neurosci 16:17–29. doi:10.1038/nrn3856 CrossRefPubMed

12.

Anderson KN, Schwab RB, Martinez ME (2014) Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast Cancer Res Treat 144:1–10. doi:10.1007/s10549-014-2852-7 CrossRefPubMedPubMedCentral

13.

Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8:253–262. doi:10.1038/nrg2045 CrossRefPubMed

14.

Zhang X, Ho SM (2011) Epigenetics meets endocrinology. J Mol Endocrinol 46:R11–R32CrossRefPubMedPubMedCentral

15.

Ulrich CM, Toriola AT, Koepl LM, Sandifer T, Poole EM, Duggan C, McTiernan A, Issa JP (2012) Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women. Epigenetics 7:1020–1028. doi:10.4161/epi.21464 CrossRefPubMedPubMedCentral

16.

Iwasaki M, Ono H, Kuchiba A, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Yoshida T, Tsugane S (2012) Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women. BMC Cancer 12:323. doi:10.1186/1471-2407-12-323 CrossRefPubMedPubMedCentral

17.

Varela-Rey M, Woodhoo A, Martinez-Chantar M-L, Mato JM, Lu SC (2013) Alcohol, DNA methylation, and cancer. Alcohol Res 35:25–35PubMedPubMedCentral

18.

Anderson OS, Sant KE, Dolinoy DC (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23:853–859. doi:10.1016/j.jnutbio.2012.03.003 CrossRefPubMedPubMedCentral

19.

Friedenreich CM, Woolcott CG, McTiernan A, Ballard-Barbash R, Brant RF et al (2010) Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncol 28:1458–1466. doi:10.1200/JCO.2009.24.9557 CrossRefPubMedPubMedCentral

20.

Friedenreich CM, Courneya KS, Neilson HK, Matthews CE, Willis G, Irwin M, Troiano R, Ballard-Barbash R (2006) Reliability and validity of the past year total physical activity questionnaire. Am J Epidemiol 163:959–970. doi:10.1093/aje/kwj112 CrossRefPubMed

21.

Csizmadi I, Kahle L, Ullman R, Dawe U, Zimmerman TP, Friedenreich CM, Bryant H, Subar AF (2007) Adaptation and evaluation of the national cancer institute’s diet history questionnaire and nutrient database for Canadian populations. Public Health Nutr 10:88–96. doi:10.1017/S1368980007184287 CrossRefPubMed

22.

Willet W, Howe G, Kushi L (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65:1220S-8S

23.

Friedenreich CM, Woolcott CG, McTiernan A, Terry T, Brant R, Ballard-Barbash R et al (2011) Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial. Int J Obes 35:427–435. doi:10.1038/ijo.2010.147 CrossRef

24.

Kile ML, Baccarelli A, Tarantini L, Hoffman E, Wright RO, Christiani DC (2010) Correlation of global and gene-specific DNA methylation in maternal-infant pairs. PLoS One 5:e13730. doi:10.1371/journal.pone.0013730 CrossRefPubMedPubMedCentral

25.

Endogenous Hormones Breast Cancer Collaborative Group (2003). Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95:1218–1226CrossRef

26.

Yang AS, Estécio MRH, Doshi K, Kondo Y, Tajara EH, Issa JP (2004) A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 32(3):e38. doi:10.1093/nar/gnh032 CrossRefPubMedPubMedCentral

27.

Zhang X, Tworoger SS, Eliassen AH, Hankinson SE (2013) Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up. Breast Cancer Res Treat 137:883–892. doi:10.1007/s10549-012-2391-z CrossRefPubMedPubMedCentral

28.

Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, Speizer F (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2–3 year period. Cancer Epidemiol Biomark Prev 4:649–654

29.

Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 1:289–300

30.

Ashbury JE, Taylor SA, Tse MY, Pang SC, Louw JA, Vanner SJ, King WD (2014) Biomarkers measured in buccal and blood leukocyte DNA as proxies for colon tissue global methylation. Int J Mol Epidemiol Genet 5:120–124PubMedPubMedCentral

31.

Chalitchagorn K, Shuangshoti S, Hourpai N, Kongruttanachok N, Tangkijvanich P, Thong-ngam D, Voravud N, Sriurangpong V, Multirangura A (2004) Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesis. Oncogene 23:8841–8846. doi:10.1038/sj.onc.1208137 CrossRefPubMed

32.

Lowe R, Slodkowicz G, Goldman N, Rakyan VK (2015) The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues. Epigenetics 10:274–281. doi:10.1080/15592294.2014.1003744 CrossRefPubMedPubMedCentral

33.

Adalsteinsson BT, Gudnason H, Aspelund T, Harris TB, Launer LJ, Eiriksdottir G, Smith AV, Gudnason V (2012) Heterogeneity in white blood cells has the potential to confound DNA methylation measurements. PLoS One 7:1–9. doi:10.1371/journal.pone.0046705 CrossRef

34.

Zhu Z-Z, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L et al (2012) Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol 41:126–139. doi:10.1093/ije/dyq154 CrossRefPubMed

Titel: Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women
verfasst von: Devon J. Boyne
Christine M. Friedenreich
John B. McIntyre
Frank Z. Stanczyk
Kerry S. Courneya
Will D. King
Publikationsdatum: 19.09.2017
Verlag: Springer International Publishing
Erschienen in: Cancer Causes & Control / Ausgabe 12/2017
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-017-0958-z

Springer Medizin

Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women