Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

Park, Hannah Lui

doi:10.3390/ijerph17041181

Cited by 16 publications

(11 citation statements)

References 177 publications

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“…Studies on epigenetic inheritance of breast cancer in humans will also need to take into account the possible interaction between ancestral exposures with lifestyle and environmental factors after birth. The good news is that there are existing multigenerational human cohorts that could be useful to study intergenerational and transgenerational breast cancer predisposition (13,91).…”

Section: Conclusion Unanswered Questions and Challengesmentioning

confidence: 99%

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Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline

et al. 2020

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The past decade has made evident that in addition to passing their genetic material at conception, parents also transmit a molecular memory of past environmental experiences, including nutritional status, to their progeny through epigenetic mechanisms. In the 1990s, it was proposed that breast cancer originates in utero. Since then, an overwhelming number of studies in human cohorts and animal models have provided support for that hypothesis. It is becoming clear, however, that exposure in the parent generation can lead to multigenerational and transgenerational inheritance of breast cancer. Importantly, recent data from our lab and others show that pre-conception paternal diets reprogram the male germline and modulate breast cancer development in offspring. This review explores the emerging evidence for transgenerational epigenetic inheritance of breast cancer focusing on studies associated with ancestral nutritional factors or related markers such as birth weight. We also explore paternal factors and the epigenetic mechanisms of inheritance through the male germline while also reviewing the existing literature on maternal exposures in pregnancy and its effects on subsequent generations. Finally, we discuss the importance of this mode of inheritance in the context of breast cancer prevention, the challenges, and outstanding research questions in the field.

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Section: Conclusion Unanswered Questions and Challengesmentioning

confidence: 99%

“…The majority of breast cancers are sporadic and thought to result from environmental and lifestyle exposures (13). Although a number of nutritional and lifestyle factors have been linked with breast cancer, these associations are mostly inconsistent (14).…”

Section: Introductionmentioning

confidence: 99%

Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline

et al. 2020

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“…Epigenetic markers, such as DNA methylation, may be a powerful tool for understanding the potential effects of glyphosate exposure in humans. White blood cell (WBC) DNA methylation has been associated with environmental exposures, 33 , 34 including endocrine-disrupting compounds, 35 , 36 other pesticides, 37 and air pollution. 38 , 39 , 40 In addition, DNA methylation indices combining information from multiple sites have been developed as biomarkers of some exposures, including smoking 41 , 42 and alcohol consumption.…”

Section: Introductionmentioning

confidence: 99%

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women

Lucia

Huang

Pathak

et al. 2022

Environ Health Perspect

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Background: Glyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure. Objective: We conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels. Methods: For 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography–tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate in of 1,000 subsamples of the study population were considered differentially methylated. Differentially methylated sites from the probe-specific analysis were combined into a methylation index. Epigenetic age acceleration from three epigenetic clocks and an epigenetic measure of pace of aging were examined for associations with glyphosate and AMPA. Results: We identified 24 CpG sites whose methylation level was associated with urinary glyphosate concentration and two associated with AMPA. Four regions, within the promoters of the MSH4 , KCNA6 , ABAT , and NDUFAF2 / ERCC8 genes, were associated with glyphosate levels, along with an association between ESR1 promoter hypomethylation and AMPA. The methylation index accurately predicted glyphosate levels in an internal validation cohort. AMPA, but not glyphosate, was associated with greater epigenetic age acceleration. Discussion: Glyphosate and AMPA exposure were associated with DNA methylation differences that could promote the development of cancer and other diseases. Further studies are warranted to replicate our results, determine the functional impact of glyphosate- and AMPA-associated differential DNA methylation, and further explore whether DNA methylation could serve as a biomarker of glyphosate exposure. https://doi.org/10.1289/EHP10174

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“…Epigenetic changes, such as DNA methylation, may serve as an intermediate phenotype for risk factors and their associated diseases [15][16][17]. As such, DNA methylation may provide a powerful tool for understanding the aetiology of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Association of mammographic density with blood DNA methylation

et al. 2021

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Background: Altered DNA methylation may be an intermediate phenotype between breast cancer risk factors and disease. Mammographic density is a strong risk factor for breast cancer. However, no studies to date have identified an epigenetic signature of mammographic density. We performed an epigenome-wide association study of mammographic density. Methods: White blood cell DNA methylation was measured for 385 postmenopausal women using the Illumina Infinium MethylationEPIC BeadChip array. Differential methylation was assessed using genome-wide, probe-level, and regional analyses. We implemented a resampling-based approach to improve the stability of our findings. Results: On average, women with elevated mammographic density exhibited DNA hypermethylation within CpG islands and gene promoters compared to women with lower mammographic density. We identified 250 CpG sites for which DNA methylation was significantly associated with mammographic density. The top sites were located within genes associated with cancer, including HDLBP, TGFB2, CCT4, and PAX8, and were more likely to be located in regulatory regions of the genome. We also identified differential DNA methylation in 37 regions, including within the promoters of PAX8 and PF4, a gene involved in the regulation of angiogenesis. Overall, our results paint a picture of epigenetic dysregulation associated with mammographic density. Conclusion: Mammographic density is associated with differential DNA methylation throughout the genome, including within genes associated with cancer. Our results suggest the potential involvement of several genes in the biological mechanisms behind differences in breast density between women. Further studies are warranted to explore these potential mechanisms and potential links to breast cancer risk.

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Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

Cited by 16 publications

References 177 publications

Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline

Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline

Association of Glyphosate Exposure with Blood DNA Methylation in a Cross-Sectional Study of Postmenopausal Women

Association of mammographic density with blood DNA methylation

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