Skip to main content Accessibility help
×
Home

Exposures in early life: associations with DNA promoter methylation in breast tumors

  • M.-H. Tao (a1), C. Marian (a2), P. G. Shields (a2), N. Potischman (a3), J. Nie (a4), S. S. Krishnan (a2), D. L. Berry (a5), B. V. Kallakury (a5), C. Ambrosone (a6), S. B. Edge (a7), M. Trevisan (a4) (a8), J. Winston (a9) and J. L. Freudenheim (a4)...

Abstract

There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.

Copyright

Corresponding author

*Address for correspondence: Dr M.-H. Tao, Institute for Translational Epidemiology, Mount Sinai School of Medicine, PO BOX 1057, New York, NY 10029, USA. Email menghua.tao@mssm.edu

References

Hide All
1.Okasha, M, McCarron, P, Gunnell, D, Smith, GD. Exposures in childhood, adolescence and early adulthood and breast cancer risk: a systematic review of the literature. Breast Cancer Res Treat. 2003; 78, 223276.
2.Burdge, GC, Lillycrop, KA, Jackson, AA. Nutrition in early life, and risk of cancer and metabolic disease: alternative endings in an epigenetic tale? Br J Nutr. 2009; 101, 619630.
3.Russo, J, Russo, IH. Development of the human breast. Maturitas. 2004; 49, 215.
4.Park, SK, Kang, D, McGlynn, KA, et al. Intrauterine environments and breast cancer risk: meta-analysis and systematic review. Breast Cancer Res. 2008; 10, R8.
5.Xu, X, Dailey, AB, Peoples-Sheps, M, et al. Birth weight as a risk factor for breast cancer: a meta-analysis of 18 epidemiological studies. J Womens Health. 2009; 18, 11691178.
6.Xue, F, Michels, KB. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol. 2007; 8, 10881100.
7.Martin, RM, Middleton, N, Gunnell, D, Owen, CG, Smith, GD. Breast-feeding and cancer: the Boyd Orr Cohort and a systematic review with meta-analysis. J Natl Cancer Inst. 2005; 97, 14461457.
8.Forman, MR, Cantwell, MM, Ronckers, C, Zhang, Y. Through the looking glass at early-life exposures and breast cancer risk. Cancer Invest. 2005; 23, 609624.
9.Ruder, EH, Dorgan, JF, Kranz, S, Kris-Etherton, PM, Hartman, TJ. Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence. Clin Breast Cancer. 2008; 8, 334342.
10.Barba, M, McCann, SE, Nie, J, et al. Perinatal exposures and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study. Cancer Causes Control. 2006; 17, 395401.
11.Green, J, Cairns, BJ, Casabonne, D, et al, for the Million Women Study collaborators.Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol. 2011; 12, 785794.
12.Waterland, RA. Is epigenetics an important link between early life events and adult disease? Horm Res. 2009; (Suppl 1), 1316.
13.Bernal, AJ, Jirtle, RL. Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res (Part A). 2010; 88, 938944.
14.Szyf, M, Pakneshan, P, Rabbani, SA. DNA methylation and breast cancer. Biochem Pharmacol. 2004; 68, 11871197.
15.Esteller, M. Epigenetics in cancer. N Engl J Med. 2008; 358, 11481159.
16.Herman, JG, Merlo, A, Mao, L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 1995; 55, 45254530.
17.Arapshian, A, Kuppumbatti, YS, Mira-y-Lopez, R. Methylation of conserved CpG sites neighboring the beta retinoic acid response element may mediate retinoic acid receptor beta gene silencing in MCF-7 breast cancer cells. Oncogene. 2000; 19, 40664070.
18.Caldeira, JR, Prando, EC, Quevedo, FC, et al. CDH1 promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer. BMC Cancer. 2006; 6, 48.
19.Desaulniers, D, Xiao, GH, Lian, H, et al. Effects of mixtures of polychlorinated biphenyls, methylmercury, and organochlorine pesticides on hepatic DNA methylation in prepubertal female Sprague-Dawley rats. Int J Toxicol. 2009; 28, 294307.
20.Heijmans, BT, Tobi, EW, Stein, AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105, 1704617049.
21.Tao, MH, Shields, PG, Nie, J, et al. DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat. 2009; 114, 559568.
22.Tao, MH, Marian, C, Nie, J, et al. Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study. Am J Clin Nutr. 2011; 94, 831838.
23.Mellemkjaer, L, Olsen, ML, Sørensen, HT, et al. Birth weight and risk of early-onset breast cancer (Denmark). Cancer Causes Control. 2003; 14, 6164.
24.Innes, K, Byers, T, Schymura, M. Birth characteristics and subsequent risk for breast cancer in very young women. Am J Epidemiol. 2000; 152, 11211128.
25.Fryer, AA, Emes, RD, Ismail, KM, et al. Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans. Epigenetics. 2011; 6, 8694.
26.La Merrill, M, Stein, CR, Landrigan, P, Engel, SM, Savitz, DA. Prepregnancy body mass index, smoking during pregnancy, and infant birth weight. Ann Epidemiol. 2011; 21, 413420
27.Flom, J, Ferris, J, Gonzalez, K, Santella, R, Terry, M. Prenatal tobacco smoke exposure and genome wide methylation in adulthood. Cancer Epidemiol Biomarkers Prev. 2011; 20, 25182523.
28.Breton, CV, Byun, HM, Wenten, M, et al. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med. 2009; 180, 462467.
29.Shah, PS, Ohlsson, A. Knowledge Synthesis group on determinants of low birth weight and preterm births. Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis. CMAJ. 2009; 180, E99E108.
30.Attig, L, Gabory, A, Junien, C. Early nutrition and epigenetic programming: chasing shadows. Curr Opin Clin Nutr Metab Care. 2010; 13, 284293.
31.Freudenheim, JL, Marshall, JR, Graham, S, et al. Exposure to breastmilk in infancy and the risk of breast cancer. Epidemiology. 1995; 5, 324331.
32.Wise, LA, Titus-Ernstoff, L, Newcomb, PA, et al. Exposure to breast milk in infancy and risk of breast cancer. Cancer Causes Control. 2009; 20, 10831089.
33.Michels, KB, Trichopoulos, D, Rosner, BA, et al. Being breastfed in infancy and breast cancer incidence in adult life: results from the two nurses’ health studies. Am J Epidemiol. 2001; 153, 275283.
34.Titus-Ernstoff, L, Egan, KM, Newcomb, PA, et al. Exposure to breast milk in infancy and adult breast cancer risk. J Natl Cancer Inst. 1998; 90, 921924.
35.Rodriguez-Palmero, M, Koletzko, B, Kunz, C, Jensen, R. Nutritional and biochemical properties of human milk: II. Lipids, micronutrients, and bioactive factors. Clin Perinatol. 1999; 26, 335359.
36.Knip, M, Virtanen, SM, Akerblom, HK. Infant feeding and the risk of type 1 diabetes. Am J Clin Nutr. 2010; 91, 1506S1513S.
37.Kang, GH, Lee, HJ, Hwang, KS, et al. Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation. Am J Pathol. 2003; 163, 15511556.
38.Issa, JP, Ahuja, N, Toyota, M, Bronner, MP, Brentnall, TA. Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res. 2001; 61, 35733577.
39.Hsieh, CC, Tzonou, A, Trichopoulos, D. Birth order and breast cancer risk. Cancer Causes Control. 1991; 2, 9598.
40.Fernandez, SV, Russo, J. Estrogen and xenoestrogens in breast cancer. Toxicol Pathol. 2010; 38, 110122.
41.Victora, CG, Adair, L, Fall, C, et al. Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008; 371, 340357.
42.Hughes, LA, van den Brandt, PA, de Bruïne, AP, et al. Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PLoS One. 2009; 4, e7951.
43.Li, L, Manor, O, Power, C. Early environment and child-to-adult growth trajectories in the 1958 British birth cohort. Am J Clin Nutr. 2004; 80, 185192.
44.Slanger, T, Mutschelknauss, E, Kropp, S, et al. Test-retest reliability of self-reported reproductive and lifestyle data in the context of a German case-control study on breast cancer and postmenopausal hormone therapy. Ann Epidemiol. 2007; 17, 993998.
45.Eads, CA, Danenberg, KD, Kawakami, K, et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 2000; 28, E32.
46.Lee, ES, Issa, JP, Roberts, DB, et al. Quantitative promoter hypermethylation analysis of cancer-related genes in salivary gland carcinomas: comparison with methylation-specific PCR technique and clinical significance. Clin Cancer Res. 2008; 14, 26642672.

Keywords

Exposures in early life: associations with DNA promoter methylation in breast tumors

  • M.-H. Tao (a1), C. Marian (a2), P. G. Shields (a2), N. Potischman (a3), J. Nie (a4), S. S. Krishnan (a2), D. L. Berry (a5), B. V. Kallakury (a5), C. Ambrosone (a6), S. B. Edge (a7), M. Trevisan (a4) (a8), J. Winston (a9) and J. L. Freudenheim (a4)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed