Molecular risk biomarkers

Molecular risk biomarkers could detect systemic or local changes indicating that the carrier of this specific biomarker is at higher risk for disease development in the future. Examples include the presence of human papillomavirus in the cervix, which is associated with a higher risk for the development of cervical cancer, the association between Hdicohacterpylori and gastric cancer as well as EBV and nasopharyngeal carcinoma. The drawback of these markers is that they are not helpful for the detection of early disease. 

Kreps SE, BanzetN, Christiani DC, Polla BS. 1997. Molecular biomarkers of early responses to environmental stressors — implications for risk assessment and pubhc health. Rev Environ Health 12 261-280. 

These above-mentioned studies quantifying bile acid reflux have been fundamental to allowing in vitro analysis of bile acid effects at physiological doses (Table 6.2). These in vitro studies have crucially, identified molecular mechanisms important in bile-driven carcinogenesis. These molecular events will undoubtedly be important in future years as drug-able targets and as biomarkers of cancer risk. Prior to bile acid quantification in the refluxate, there... 

Environmental Cancer Risk, Nutrition, and Individual Susceptibility (ECNIS) Studying use of biomarkers of exposure and susceptibility and bioindicators of disease in molecular epidemiology of cancer (ECNIS 2005). 

Bonassi, S., and W.W. Au. 2002. Biomarkers in molecular epidemiology studies for health risk prediction. Mutat. Res. 511(l) 73-86. 

Biomarkers can also be used to identify factors that increase the likelihood that an individual will develop disease. This is an important area of research in molecular epidemiology as it becomes more evident that not all risk factors will contribute to disease equally across the human population. Therefore, in order to determine whether an environmental agent is related to disease, those factors that are also required for disease development need to be taken into account. Otherwise, many disease risk factors may go undetected. Examples of susceptibility factors that can be ascertained using biomarkers are some viral infections, which may predispose to specific diseases (for example, HIV infection and Kaposi sarcoma) or HBV infection and liver cancer. Biomarkers can also be used to measure dietary factors that can contribute to disease. The most common susceptibility factor studied using a molecular epidemiological approach are hereditary factors, which are discussed in the following section. 

Biomarkers are defined as any cellular or molecular indication of toxic exposure, adverse health outcome or susceptibility (NAS, 1987). From this definition, three distinct biomarkers are evident, that of exposure, effects of exposure, and host susceptibility. As more extensively discussed by Maier et al. (2001), this field has progressed to a point where application to risk assessment is possible. For example, biomarkers of effects, exposure, and host susceptibility can give insights into mode of chemical action. These insights are likely to better inform the hazard... 

Rossi F, Bellini G, Tolone C et al (2012) The cannabinoid receptor type 2 Q63R variant increases the risk of celiac disease implication for a novel molecular biomarker and future therapeutic intervention. Pharmacol Res 66 88-94... 

Among molecular biomarkers, DNA adducts such as 8-hydroxy-dG, Ml-dG, and PhIP-DNA, discussed in Chapter 7, represent potential candidates for the assessment of the efficacy of an intervention study however, as pointed out recently by Halliwell [7], there is considerable circumstantial evidence rather than proof beyond reasonable doubt as to the validity of oxidative DNA as a biomarker of subsequent cancer development. As well as validated biomarkers, interlaboratory agreement is urgently needed on their protocols and use. Developments in functional trinomics will facilitate characterization of molecular and genomic biomarkers that can be used to determine risk in prospective cohorts as well as surrogate endpoints in clinical studies. 

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