Top

10-11-2017 | Breast cancer | Article

Body mass index, diet, and exercise: testing possible linkages to breast cancer risk via DNA methylation

Journal: Breast Cancer Research and Treatment

Authors: Arielle S. Gillman, Casey K. Gardiner, Claire E. Koljack, Angela D. Bryan

Publisher: Springer US

Abstract

Purpose

To examine DNA methylation as a mechanism linking diet, physical activity, weight status, and breast cancer risk.

Methods

Insufficiently active women of varying weight status, without a history of cancer, completed a maximal exercise test, clinical measurement of height and weight, and a dietary intake measure. They also provided blood samples, which were analyzed to ascertain average methylation of candidate genes related to breast cancer (BRCA1, RUNX3, GALNT9, and PAX6) and inflammation (TLR4 and TLR6).

Results

Elevated weight status (r = − .18, p < .05) and poorer aerobic fitness (r = .24, p < .01) were each associated with decreased methylation of inflammation genes. Methylation of inflammation genes statistically mediated the relationship between weight status and cancer gene methylation (standardized indirect effect = .12, p < .05) as well as between cardiorespiratory fitness and cancer gene methylation (standardized indirect effect = − .172, p < .01). However, recent dietary behavior was not associated with methylation of either inflammation or cancer genes.

Conclusions

Both weight status and cardiovascular fitness are associated with methylation of genes associated with both inflammation and cancer. Methylation of inflammatory genes might serve as a mechanistic link between lifestyle factors and methylation changes in genes that increase risk for breast cancer.

Howlader N, Noone AM, Krapcho M et al (2011) SEER cancer statistics review, 1975–2009 (vintage 2009 populations). National Cancer Institute, Bethesda

Ogden CL, Carroll MD, Fryar CD, Flegal KM (2015) Prevalence of obesity among adults and youth: United States, 2011–2014. NCHS Data Brief 219:1–8

Ligibel JA, Alfano CM, Courneya KS et al (2014) American society of clinical oncology position statement on obesity and cancer. J Clin Oncol 32:3568–3574. https://doi.org/10.1200/JCO.2014.58.4680 CrossRefPubMedPubMedCentral

Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348:1625–1638CrossRefPubMed

Park J, Morley TS, Kim M et al (2014) Obesity and cancer—mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol 10:455–465. https://doi.org/10.1038/nrendo.2014.94 CrossRefPubMedPubMedCentral

Aljadani HM, Patterson A, Sibbritt D et al (2013) Diet quality, measured by fruit and vegetable intake, predicts weight change in young women. J Obes. https://doi.org/10.1155/2013/525161 PubMedPubMedCentral

He K, Hu FB, Colditz GA et al (2004) Changes in intake of fruits and vegetables in relation to risk of obesity and weight gain among middle-aged women. Int J Obes 28:1569–1574. https://doi.org/10.1038/sj.ijo.0802795 CrossRef

Key TJ, Allen NE, Spencer EA, Travis RC (2002) The effect of diet on risk of cancer. Lancet 360:861–868. https://doi.org/10.1016/S0140-6736(02)09958-0 CrossRefPubMed

Steinmetz KA, Potter JD (1996) Vegetables, fruit, and cancer prevention. J Am Diet Assoc 96:1027–1039. https://doi.org/10.1016/S0002-8223(96)00273-8 CrossRefPubMed

10.

Monninkhof EM, Elias SG, Vlems FA et al (2007) Physical activity and breast cancer: a systematic review. Epidemiology 18:137–157CrossRefPubMed

11.

Lynch BM, Neilson HK, Friedenreich CM (2010) Physical activity and breast cancer prevention. Physical activity and cancer. Springer, New york, pp 13–42CrossRef

12.

Dimeo FC, Stieglitz R, Novelli-Fischer U et al (1999) Effects of physical activity on the fatigue and psychologic status of cancer patients during chemotherapy. Cancer 85:2273–2277CrossRefPubMed

13.

Ibrahim EM, Al-Homaidh A (2011) Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol 28:753–765CrossRefPubMed

14.

Font-Burgada J, Sun B, Karin M (2016) Obesity and cancer: the oil that feeds the flame. Cell Metab 23:48–62. https://doi.org/10.1016/j.cmet.2015.12.015 CrossRefPubMed

15.

Tobias DK, Akinkuolie AO, Chandler PD et al (2017) Markers of inflammation and incident breast cancer risk in the Women’s health study. Am. J, Epidemiol

16.

Woods JA, Vieira VJ, Keylock KT (2009) Exercise, inflammation, and innate immunity. Immunol Allergy Clin North Am 29:381–393. https://doi.org/10.1016/j.iac.2009.02.011 CrossRefPubMed

17.

Calder PC, Ahluwalia N, Brouns F et al (2011) Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr 106:S5–S78. https://doi.org/10.1017/S0007114511005460 CrossRefPubMed

18.

Xu X, Su S, Barnes VA et al (2013) A genome-wide methylation study on obesity. Epigenetics 8:522–533. https://doi.org/10.4161/epi.24506 CrossRefPubMedPubMedCentral

19.

Ronn T, Volkov P, Gillberg L et al (2015) Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood. Hum Mol Genet 100:9440–9445. https://doi.org/10.1093/hmg/ddv124

20.

Higdon J, Delage B, Williams D, Dashwood R (2007) Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res 55:224–236. https://doi.org/10.1016/j.phrs.2007.01.009 CrossRefPubMedPubMedCentral

21.

Li Y, Tollefsbol TO (2010) Impact on DNA methylation in cancer prevention and therapy by bioactive dietary components. Curr Med Chem 17:2141–2151. https://doi.org/10.2174/092986710791299966 CrossRefPubMedPubMedCentral

22.

Zhang FF, Morabia A, Carroll J et al (2011) Dietary patterns are associated with levels of global genomic DNA methylation in a cancer-free population. J Nutr 141:1165–1171. https://doi.org/10.3945/jn.110.134536 CrossRefPubMedPubMedCentral

23.

Coyle YM, Xie X-J, Lewis CM et al (2007) Role of physical activity in modulating breast cancer risk as defined by APC and RASSF1A promoter hypermethylation in nonmalignant breast tissue. Cancer Epidemiol Prev Biomark 16:192–196CrossRef

24.

Bryan AD, Magnan RE, Hooper AEC et al (2013) Physical activity and differential methylation of breast cancer genes assayed from saliva: a preliminary investigation. Ann Behav Med 45:89–98. https://doi.org/10.1007/s12160-012-9411-4 CrossRefPubMedPubMedCentral

25.

Zhang FF, Cardarelli R, Carroll J et al (2011) Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics 6:293–299. https://doi.org/10.4161/epi.6.3.14378 CrossRefPubMedPubMedCentral

26.

Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680CrossRefPubMed

27.

Yang H, Zhou H, Feng P et al (2010) Reduced expression of toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion. J Exp Clin Cancer Res 29:92CrossRefPubMedPubMedCentral

28.

Lau QC, Raja E, Salto-Tellez M et al (2006) RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res 66:6512–6520CrossRefPubMed

29.

Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3:415–428CrossRefPubMed

30.

Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225–3229PubMed

31.

Belinsky SA, Palmisano WA, Gilliland FD et al (2002) Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res 62:2370–2377PubMed

32.

Ortega FB, Ruiz JR, Labayen I et al (2017) The fat but fit paradox: what we know and don’t know about it. Br J Sports Med. https://doi.org/10.1136/bjsports-2016-097400

33.

Pierce JP, Stefanick ML, Flatt SW et al (2007) Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 25:2345–2351. https://doi.org/10.1200/JCO.2006.08.6819 CrossRefPubMedPubMedCentral

34.

Satia JA, Watters JL, Galanko JA (2009) Validation of an antioxidant nutrient questionnaire in whites and African Americans. J Am Diet Assoc 109(502–508):e6

35.

Reed K, Poulin ML, Yan L, Parissenti AM (2010) Comparison of bisulfite sequencing PCR with pyrosequencing for measuring differences in DNA methylation. Anal Biochem 397:96–106CrossRefPubMed

36.

Esteller M, Silva JM, Dominguez G et al (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. JNCI J Natl Cancer Inst 92:564–569CrossRefPubMed

37.

Pangeni RP, Channathodiyil P, Huen DS et al (2015) The GALNT9, BNC1 and CCDC8 genes are frequently epigenetically dysregulated in breast tumours that metastasise to the brain. Clin Epigenetics 7:57CrossRefPubMedPubMedCentral

38.

Toyota M, Ho C, Ahuja N et al (1999) Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 59:2307–2312PubMed

39.

Bryan A, Schmiege SJ, Broaddus MR (2007) Mediational analysis in hiv/aids research: estimating multivariate path analytic models in a structural equation modeling framework. AIDS Behav 11:365–383. https://doi.org/10.1007/s10461-006-9150-2 CrossRefPubMed

40.

Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591. https://doi.org/10.1038/nrc1408 CrossRefPubMed

41.

Ehrlich M (2002) DNA methylation in cancer: too much, but also too little. Oncogene 21:5400–5413. https://doi.org/10.1038/sj.onc.1205651 CrossRefPubMed