Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study

Tao, Meng Hua; Marian, Cătălin; Nie, Jing; Ambrosone, Christine B.; Krishnan, Shiva; Edge, Stephen B.; Trevisan, Maurizio; Shields, Peter G.; Freudenheim, Jo L.

doi:10.3945/ajcn.110.009365

Cited by 20 publications

(24 citation statements)

References 45 publications

(56 reference statements)

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“…Given our emphasis on the tumor tissue, the most relevant previous research for our purposes are studies of breast tumor methylation and BMI (13, 46). In one study, Tao et al examined the association between obesity and methylation in three candidate genes, E-cadherin, p16 , and RAR-β(2) , in breast tumor tissue, and showed no statistically significant differences in percentage methylation by BMI status in their study population; regression analyses stratified by ER status were not reported (13). Though the three genes examined by Tao et al (13) were represented on our methylation panel, we were unable to ascertain the exact CpG loci on which methylation values were measured.…”

Section: Discussionmentioning

confidence: 99%

“…In one study, Tao et al examined the association between obesity and methylation in three candidate genes, E-cadherin, p16 , and RAR-β(2) , in breast tumor tissue, and showed no statistically significant differences in percentage methylation by BMI status in their study population; regression analyses stratified by ER status were not reported (13). Though the three genes examined by Tao et al (13) were represented on our methylation panel, we were unable to ascertain the exact CpG loci on which methylation values were measured. Given that DNA methylation levels can vary greatly within short base pair distances (47), we were unable to meaningfully compare our gene methylation results with those of Tao et al In another study, Naudshad et al examined the association between BMI and methylation in Ec-SOD, RASSF1, BRCA1 , and BNIP3 ; all of the gene loci except for BNIP3 were significantly, increasingly methylated with higher BMI while BNIP3 was significantly, inversely associated with BMI (46).…”

Section: Discussionmentioning

confidence: 99%

“…Though obesity has been associated with increased methylation in several cancer-related genes (11, 12), previous research has been limited by the use of white blood cells instead of breast tissue (11, 12) or by focusing on only candidate genes (13). We sought to test whether obesity is associated with methylation in a panel of cancer-related genes in the tumor tissue of women diagnosed with breast cancer.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor–Positive Breast Tumors

Hair

Troester

Edmiston

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Although obesity is associated with breast cancer incidence and prognosis, the underlying mechanisms are poorly understood. Identification of obesity-associated epigenetic changes in breast tissue may advance mechanistic understanding of breast cancer initiation and progression. The goal of this study, therefore, was to investigate associations between obesity and gene methylation in breast tumors. Methods Using the Illumina GoldenGate Cancer I Panel, we estimated the association between body mass index (BMI) and gene methylation in 345 breast tumor samples from Phase I of the Carolina Breast Cancer Study, a population based case-control study. Multivariable linear regression was used to identify sites that were differentially methylated by BMI. Stratification by tumor estrogen receptor status was also conducted. Results In the majority of the 935 probes analyzed (87%), the average beta value increased with obesity (BMI ≥ 30). Obesity was significantly associated with differential methylation (false discovery rate q-value < 0.05) in just 2 gene loci in breast tumor tissue overall and in 21 loci among estrogen receptor (ER)-positive tumors. Obesity was associated with methylation of genes that function in immune response, cell growth, and DNA repair. Conclusions Obesity is associated with altered methylation overall, and with hypermethylation among ER-positive tumors in particular, suggesting that obesity may influence the methylation of genes with known relevance to cancer. Some of these differences in methylation by obese status may influences levels of gene expression within breast cells. Impact If our results are validated, obesity-associated methylation sites could serve as targets for prevention and treatment research.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor–Positive Breast Tumors

Hair

Troester

Edmiston

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…2,3 Hypermethylation of DNA in promoter regions of tumor suppressor genes (TSG) such as p16, ER-a, PR, BRCA1, GSTP1, TIMP-4, and CDH1 is known to be a major event in breast carcinogenesis. 4 Several breast cancer risk factors, [5][6][7][8] including race, 2,9 have been reported to increase the risk of altered DNA methylation in breast tumors.…”

Section: Introductionmentioning

confidence: 99%

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

et al. 2015

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Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n D 61) and AAs (n D 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.

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“…These studies evaluated either non-diseased or tumor breast tissue, but did not find any significant associations [46, 47]. However, these studies were limited by small strata [47] and did not use a genome-wide approach [46, 47]. …”

Section: Discussionmentioning

confidence: 99%

Body mass index associated with genome-wide methylation in breast tissue

Hair

Kirk

et al. 2015

Breast Cancer Res Treat

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Gene expression studies indicate that body mass index (BMI) is associated with molecular pathways involved in inflammation, insulin-like growth factor activation, and other carcinogenic processes in breast tissue. The goal of this study was to determine whether BMI is associated with gene methylation in breast tissue and to identify pathways that are commonly methylated in association with high BMI. Epigenome-wide methylation profiles were determined using the Illumina HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women undergoing breast surgery between 2009 and 2013 at the University of North Carolina Hospitals. Multivariable, robust linear regression was performed to identify methylation sites associated with BMI at a false discovery rate q value <0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes.

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Body mass and DNA promoter methylation in breast tumors in the Western New York Exposures and Breast Cancer Study

Cited by 20 publications

References 45 publications

Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor–Positive Breast Tumors

Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor–Positive Breast Tumors

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

Body mass index associated with genome-wide methylation in breast tissue

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