Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research

Michaud, Dominique S.; Houseman, E. Andrés; Marsit, Carmen J.; Nelson, Heather H.; Wiencke, John K.; Kelsey, Karl T.

doi:10.1158/1055-9965.epi-15-0681

Cited by 19 publications

(17 citation statements)

References 121 publications

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“…Smoking can strongly affect immune cell composition [21,35] although in our small study we observed only modest, nonsignificant differences between nonsmokers and smokers (based on either computation or complete blood counts, Tables 1 and 2, S2A–S2F Fig). Relative leukocyte composition (Fig 3) in relationship to relative change in cell-type composition and cell-type specific methylation effects may combine to produce different measured outcomes in whole blood.…”

Section: Resultsmentioning

confidence: 69%

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Su¹,

Wang²,

Campbell³

et al. 2016

PLoS ONE

106

124

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Tobacco smoke exposure dramatically alters DNA methylation in blood cells and may mediate smoking-associated complex diseases through effects on immune cell function. However, knowledge of smoking effects in specific leukocyte subtypes is limited. To better characterize smoking–associated methylation changes in whole blood and leukocyte subtypes, we used Illumina 450K arrays and Reduced Representation Bisulfite Sequencing (RRBS) to assess genome-wide DNA methylation. Differential methylation analysis in whole blood DNA from 172 smokers and 81 nonsmokers revealed 738 CpGs, including 616 previously unreported CpGs, genome-wide significantly associated with current smoking (p <1.2x10-7, Bonferroni correction). Several CpGs (MTSS1, NKX6-2, BTG2) were associated with smoking duration among heavy smokers (>22 cigarettes/day, n = 86) which might relate to long-term heavy-smoking pathology. In purified leukocyte subtypes from an independent group of 20 smokers and 14 nonsmokers we further examined methylation and gene expression for selected genes among CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, and CD2+ T cells. In 10 smokers and 10 nonsmokers we used RRBS to fine map differential methylation in CD4+ T cells, CD8+ T cells, CD14+, CD15+, CD19+, and CD56+ natural killer cells. Distinct cell-type differences in smoking-associated methylation and gene expression were identified. AHRR (cg05575921), ALPPL2 (cg21566642), GFI1 (cg09935388), IER3 (cg06126421) and F2RL3 (cg03636183) showed a distinct pattern of significant smoking-associated methylation differences across cell types: granulocytes> monocytes>> B cells. In contrast GPR15 (cg19859270) was highly significant in T and B cells and ITGAL (cg09099830) significant only in T cells. Numerous other CpGs displayed distinctive cell-type responses to tobacco smoke exposure that were not apparent in whole blood DNA. Assessing the overlap between these CpG sites and differential methylated regions (DMRs) with RRBS in 6 cell types, we confirmed cell-type specificity in the context of DMRs. We identified new CpGs associated with current smoking, pack-years, duration, and revealed unique profiles of smoking-associated DNA methylation and gene expression among immune cell types, providing potential clues to hematopoietic lineage-specific effects in disease etiology.

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Section: Resultsmentioning

confidence: 69%

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Su¹,

Wang²,

Campbell³

et al. 2016

PLoS ONE

106

124

View full text Add to dashboard Cite

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“…Tumours in different stages have different characteristics. However, inflammation and immune changes in tumour growth and also plays an important role in the process of treatment [43, 44]. In our research, the transcriptional regulatory pathway of inflammation and immune disorders of AD and BC were first studied, and other kinds of neurodegenerative diseases and cancers will be studied in the next step.…”

Section: Discussionmentioning

confidence: 99%

Differences of immune disorders between Alzheimer’s disease and breast cancer based on transcriptional regulation

et al. 2017

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Although chronic inflammation and immune disorders are of great importance to the pathogenesis of both dementia and cancer, the pathophysiological mechanisms are not clearly understood. In recent years, growing epidemiological evidence and meta-analysis data suggest an inverse association between Alzheimer’s disease (AD), which is the most common form of dementia, and cancer. It has been revealed that some common genes and biological processes play opposite roles in AD and cancer; however, the biological immune mechanism for the inverse association is not clearly defined. An unsupervised matrix decomposition two-stage bioinformatics procedure was adopted to investigate the opposite behaviors of the immune response in AD and breast cancer (BC) and to discover the underlying transcriptional regulatory mechanisms. Fast independent component analysis (FastICA) was applied to extract significant genes from AD and BC microarray gene expression data. Based on the extracted data, the shared transcription factors (TFs) from AD and BC were captured. Second, the network component analysis (NCA) algorithm in this study was presented to quantitatively deduce the TF activities and regulatory influences because quantitative dynamic regulatory information for TFs is not available via microarray techniques. Based on the NCA results and reconstructed transcriptional regulatory networks, inverse regulatory processes and some known innate immune responses were described in detail. Many of the shared TFs and their regulatory processes were found to be closely related to the adaptive immune response from dramatically different directions and to play crucial roles in both AD and BC pathogenesis. From the above findings, the opposing cellular behaviors demonstrate an invaluable opportunity to gain insights into the pathogenesis of these two types of diseases and to aid in developing new treatments.

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“…A history of PyV infection assessed through antibody detection against a viral antigen implies that either viral action or confounding by an immune trait (80) related to both infection and SCC risk may be responsible for skin carcinogenesis. BK and JC are known to reactivate under conditions of immunosuppression (e.g., organ transplantation) due to impaired cellular immune responses and decreased immune surveillance (22, 81, 82).…”

Section: Discussionmentioning

confidence: 99%

“…Further, we previously found specific PyVs to be associated with slight changes in adaptive lymphocyte proportions among immunocompetent individuals using a bioinformatics approach (83). As adaptive immunity is modulated by both genetics and exposure to infections or allergens, and plays a role in future cancer risk, research causally linking viruses and SCC is complicated by their shared association with immune dysfunction (80). …”

Section: Discussionmentioning

confidence: 99%

Prospective Study of Human Polyomaviruses and Risk of Cutaneous Squamous Cell Carcinoma in the United States

Gossai

Waterboer

Nelson

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Merkel cell polyomavirus (PyV) is causally related to Merkel cell carcinoma, a rare skin malignancy. Little is known about the serostability of other PyVs over time or associations with cutaneous squamous cell carcinoma (SCC).Methods: As part of a U.S. nested case-control study, antibody response against the PyV VP1 capsid proteins of BK and John Cunningham virus (JC) was measured using multiplex serology on 113 SCC cases and 229 gender, age, and study center-matched controls who had a prior keratinocyte cancer. Repeated serum samples from controls and both pre and postdiagnosis samples from a subset of SCC cases were also tested. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using conditional logistic regression.

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Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research

Cited by 19 publications

References 121 publications

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Distinct Epigenetic Effects of Tobacco Smoking in Whole Blood and among Leukocyte Subtypes

Differences of immune disorders between Alzheimer’s disease and breast cancer based on transcriptional regulation

Prospective Study of Human Polyomaviruses and Risk of Cutaneous Squamous Cell Carcinoma in the United States

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