Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology

Ogino, Shuji; Nowak, Jonathan A.; Hamada, Tsuyoshi; Milner, Danny A.; Nishihara, Reiko

doi:10.1146/annurev-pathmechdis-012418-012818

Cited by 186 publications

(149 citation statements)

References 157 publications

(172 reference statements)

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“…Recent technological advances are enabling the development of emerging research fields such as the Molecular Pathological Epidemiology (MPE) incorporating interpersonal heterogeneity of a disease process into epidemiology (Hamada, Keum, Nishihara, & Ogino, ). In this framework the integration of data capturing the complex combination of genetic heterogeneity (endogenous factors) and the environment (exogenous factors) is providing novel insights underlying etiologic mechanisms of different cancer types (Ogino, Nowak, Hamada, Milner Jr, & Nishihara, ) and define new therapeutic strategies (Ogino et al, ).…”

Section: Resultsmentioning

confidence: 99%

Integrating molecular networks with genetic variant interpretation for precision medicine

Capriotti

Öztürk

Carter

2018

WIREs Mechanisms of Disease

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More reliable and cheaper sequencing technologies have revealed the vast mutational landscapes characteristic of many phenotypes. The analysis of such genetic variants has led to successful identification of altered proteins underlying many Mendelian disorders. Nevertheless the simple one‐variant one‐phenotype model valid for many monogenic diseases does not capture the complexity of polygenic traits and disorders. Although experimental and computational approaches have improved detection of functionally deleterious variants and important interactions between gene products, the development of comprehensive models relating genotype and phenotypes remains a challenge in the field of genomic medicine. In this context, a new view of the pathologic state as significant perturbation of the network of interactions between biomolecules is crucial for the identification of biochemical pathways associated with complex phenotypes. Seminal studies in systems biology combined the analysis of genetic variation with protein–protein interaction networks to demonstrate that even as biological systems evolve to be robust to genetic variation, their topologies create disease vulnerabilities. More recent analyses model the impact of genetic variants as changes to the “wiring” of the interactome to better capture heterogeneity in genotype–phenotype relationships. These studies lay the foundation for using networks to predict variant effects at scale using machine‐learning or algorithmic approaches. A wealth of databases and resources for the annotation of genotype–phenotype relationships have been developed to support developments in this area. This overview describes how study of the molecular interactome has generated insights linking the organization of biological systems to disease mechanism, and how this information can enable precision medicine. This article is categorized under: Translational, Genomic, and Systems Medicine > Translational Medicine Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Computational Methods

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Section: Resultsmentioning

confidence: 99%

Integrating molecular networks with genetic variant interpretation for precision medicine

Capriotti

Öztürk

Carter

2018

WIREs Mechanisms of Disease

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“…Intake of dietary calcium, dairy calcium, and calcium supplement and risk of colorectal cancer according to densities of tumor-infiltrating T-cell subsets in the NHS the cohorts. The integration of tumor immunology analyses into the framework of molecular pathologic epidemiology is an emerging research area (49,50), which enabled us to better understand etiologic heterogeneity according to tumor molecular and immune features. However, several limitations should be noted.…”

Section: Discussionmentioning

confidence: 99%

Calcium Intake and Risk of Colorectal Cancer According to Tumor-infiltrating T Cells

Yang

Liu

Keum

et al. 2019

Cancer Prevention Research

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Calcium intake has been associated with a lower risk of colorectal cancer. Calcium signaling may enhance T-cell proliferation and differentiation, and contribute to T-cell-mediated antitumor immunity. In this prospective cohort study, we investigated the association between calcium intake and colorectal cancer risk according to tumor immunity status to provide additional insights into the role of calcium in colorectal carcinogenesis. The densities of tumor-infiltrating T-cell subsets [CD3 þ , CD8 þ , CD45RO (PTPRC) þ , or FOXP3 þ cell] were assessed using IHC and computerassisted image analysis in 736 cancer cases that developed among 136,249 individuals in two cohorts. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Total calcium intake was associated with a multivariable HR of 0.55 (comparing 1,200 vs. <600 mg/day; 95% CI, 0.36-0.84; P trend ¼ 0.002) for CD8 þ T-cell-low but not for CD8 þ T-cell-high tumors (HR ¼ 1.02; 95% CI, 0.67-1.55; P trend ¼ 0.47). Similarly, the corresponding HRs (95% CIs) for calcium for low versus high T-cellinfiltrated tumors were 0.63 (0.42-0.94; P trend ¼ 0.01) and 0.89 (0.58-1.35; P trend ¼ 0.20) for CD3 þ ; 0.58 (0.39-0.87; P trend ¼ 0.006) and 1.04 (0.69-1.58; P trend ¼ 0.54) for CD45RO þ ; and 0.56 (0.36-0.85; P trend ¼ 0.006) and 1.10 (0.72-1.67; P trend ¼ 0.47) for FOXP3 þ , although the differences by subtypes defined by T-cell density were not statistically significant. These potential differential associations generally appeared consistent regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status. Our findings suggest a possible role of calcium in cancer immunoprevention via modulation of T-cell function.

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“…An MPE study was conducted to test this association and found that a diet rich in fiber and whole grains was associated with a decreased risk of colorectal cancer in persons containing F. nucleatum, suggesting decreased carcinogenesis through suppression of this microorganism. Further MPE studies on pathogenic interactions between the environment, immune system and tumor cells will shed light upon the mechanisms of the effect of ecosystem disruption on human immune system dysfunction and other epigenetic modification of our body, which in turn contributes to tumorigenesis [15,16].…”

Section: Ecosystem and Cancermentioning

confidence: 99%

Recognizing the Effect of Ecosystem Disruption on Human Health and Neurodevelopment

Ming

Ray

2019

IJERPH

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The topics of climate change and ecosystem disruption are at the forefront of global discussion. Accordingly, there is a sense of urgency among citizens, environmental experts, and political leaders for action and policy change. While the effect of a changing climate on the environment is well recognized, its impact on the human body has not been sufficiently described. In our review, we will attempt to outline some of these effects. We will discuss how the recent surge of immunologic disease may be related to the changing profile of microorganisms and antigens in our every-day environment. We will explore how the introduction of antibiotics may result in an altered gut microbiome, and subsequently abnormal neurodevelopment. Finally, we will discuss a possible link between chemical preservatives and neoplastic disease.

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Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology

Cited by 186 publications

References 157 publications

Integrating molecular networks with genetic variant interpretation for precision medicine

Integrating molecular networks with genetic variant interpretation for precision medicine

Calcium Intake and Risk of Colorectal Cancer According to Tumor-infiltrating T Cells

Recognizing the Effect of Ecosystem Disruption on Human Health and Neurodevelopment

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