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Correlation between nutritional biomarkers and breast cancer: a case-control study.

A case-control study to explore associations between retinoids, tocopherols, total and beta-carotenes and breast cancer was conducted by analysing concentrations of these biomarkers in adipose tissue, cheek cells and plasma. A total of 414 French-Canadians in Montreal with new diagnoses of breast cancer were age-matched to 429 population-based controls. Subjects were interviewed using a questionnaire, and biological samples from 287 cases and 112 controls were collected within 3 months of the diagnosis. Mean beta carotene concentrations in cheek cells were significantly lower among controls. Odds ratios (ORs) from logistic regression analysis were used to compare higher and lower tercile concentrations. Significant positive associations were observed in adipose tissue for retinoid [OR=2.11; 95% CI (1.09-4.08)] and beta carotene [OR=3.18; 95% CI (1.70-5.93)]; in cheek cells for beta carotene [OR=2.22; 95% CI (1.21-4.50)] and for total carotenes [OR=2.94; 95% CI (1.59-5.42)] and in plasma for beta carotene [OR=1.53; 95% CI (0.80-2.93)] and total carotenes [OR=1.04; 95% CI (0.53-2.05)]. Among the control groups, significant Pearson correlations were observed between cheek cells and adipose tissue for total carotenes (r=0.27; p=0.01) and cheek cells and plasma (r=0.22; p=0.04). In contrast to previous works, this study shows that high concentrations of retinoids and carotenes in adipose tissue and cheek cells are associated with increased risk of breast cancer. However, all these studies are limited by small sample size. Although our study tested a limited number of controls, important associations were observed. These results suggest that the effect of disease on biomarkers is fundamental to the interpretation of epidemiological data. We suggest either that the high levels of these biomarkers found in cancer patients in this study may be due to the disease process that affects the pharmacokinetics of the biomarker or that the disease causes a change in dietary habits. In addition, in studies involving the application of biomarkers to cancer epidemiology it is imperative that a typical biomarker concentration is not associated with breast cancer risk before further examination of the methodological limitations of epidemiological studies investigating this relationship. Therefore, sample size, selection bias, information bias, and confounding should be considered in the design of studies investigating the aetiological relationship between biomarkers and breast cancer.

Adipose Tissue↗

Gap analysis of pediatric reference intervals for risk biomarkers of cardiovascular disease and the metabolic syndrome.

The childhood obesity epidemic has begun to compromise the health of the pediatric population by promoting premature development of atherosclerosis and the metabolic syndrome (MS), both of which significantly increase the risk of cardiovascular disease (CVD) early in life. As a result, recently, there has been increased recognition of the need to assess and closely monitor children and adolescents for risk factors of CVD and components of the MS. Serum/Plasma biomarkers including total cholesterol, triglycerides, HDL-C, LDL-C, insulin and C-peptide have been used for this purpose for many years. Recently, emerging biomarkers such as apolipoprotein AI, apolipoprotein B, leptin, adiponectin, free fatty acids, and ghrelin have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers, if not more powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender, pubertal stage, and ethnic origin are a necessity. Unfortunately, to date, many critical gaps exist in the reference interval database of most of the biomarkers that have been identified. This review contains a comprehensive gap analysis of the reference intervals for emerging and traditional risk biomarkers of CVD and the MS and discusses the clinical significance and analytical considerations of each biomarker.

Biomarkers↗

Multimodal alignment improves generalizability of genomic biomarker prediction in computational pathology.

Computational pathology models that use digitized histopathology whole-slide images have the potential to become a cost-effective and scalable alternative to molecular assays for the prediction of genomic biomarkers, a key task in precision oncology. However, as new genomic biomarkers are discovered or quantified, large, labeled datasets must be prospectively collected to train new models. To address this challenge, we developed multimodal alignment for biomarker learning and generalization (MARBLE), a multimodal contrastive pretraining strategy that integrates structured biomarker knowledge into representation learning of histopathology images. MARBLE aligns histopathology-derived representations with representations of genomic biomarkers generated by a large language model (LLM) and a protein language model (PLM). This biologically informed alignment enables data-efficient generalization to novel, out-of-distribution biomarkers. Using the MSK-IMPACT cohort of over 40,000 patients across multiple biomarker panel versions, we design experiments grounded in real-world data to demonstrate the value of our proposed approach.

CP: computational biology↗

Circulating biomarkers from tumour bulk to tumour machinery: promises and pitfalls.

In this paper, we provide a working classification for circulating biomarkers according to their potential clinical application. We broadly divided biomarkers into four groups: (i) biomarkers of cancer risk, (ii) biomarkers of tumour-host interactions, (iii) biomarker of tumour burden, and (iv) function-related biomarkers. We hope this classification will provide a framework to which the results of future studies can be added. We also discuss the promises and pitfalls in the optional use of biomarkers in oncology.

Biomarkers, Tumor↗

Validity of human nails as a biomarker of arsenic and selenium exposure: A review.

Human nail clippings have been used in recent epidemiological studies as a routine bioindicator of arsenic and selenium exposure. To ensure sound application of this biomarker, however, it is important to consider properties and scientific knowledge pertaining to validation of this particular tool. In this review, the use of human nails to measure exposure to arsenic and selenium is discussed in the context of the biomarker validation framework. Literature related to both analytical procedures and intrinsic characteristics of the biomarker is reviewed. Specifically, the followings are addressed: sample collection and preparation methods, establishment of the exposure-biomarker relationship, intraindividual variability and reproducibility of measurements, and biomarker-disease investigations. Drawing from a rapidly growing body of literature, current knowledge of these biomarker validation steps is assessed. Therefore, this review brings attention to the important issue of biomarker validation, laying the framework for future studies measuring elemental composition of nails.

Arsenic↗

Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl diisocyanate (pMDI) and its glutathione adduct.

Hemoglobin adducts (Hb-MDX) of monomeric methylenediphenyl diisocyanate (MDI) are often interpreted as indirect evidence of hydrolysis of the diisocyanate moiety to the respective amine (diphenylmethane-4,4'-diamine, 4,4'-MDA) which constitutes the rationale of using this biomarker as an internal dosimeter of exposure to putatively formed MDA. In contrast, more recently published data suggest that following inhalation the high concentration of glutathione (GSH) present in lungs favor an adduct formation with GSH and/or peptides/proteins rather than hydrolysis. The focus of this study was to test this alternate hypothesis, viz. whether Hb-MDX can also be formed by the GSH bis-adduct of monomeric MDI. The synthesized mMDI-GSH bis-adduct was administered to rats by single intratracheal instillation. Additional groups were dosed by gavage and intraperitoneal injection. Biomarkers of exposure were determined in blood (plasma protein and hemoglobin adducts) and urine after harsh alkaline and acid hydrolysis, respectively. Data from previous single inhalation exposure studies with aerosols of MDI and 4,4'-MDA in rats served as reference. As to whether N-acetylation plays any modifying role to yield these mMDI-specific biomarkers was addressed in similarly head-only exposed dogs, a species with no appreciable N-acetylation capacity whereas rats are strong N-acetylators. The results obtained suggest that biomarkers in blood from controlled exposures above current workplace standards of mMDI appear not to be suitable for reliable assessments of past exposures. The biomarkers typically used to assess past exposures to MDI were also identified following exposure to the MDI-GSH bis-adduct. Their yield was low but quite similar for MDI aerosol and the MDI-GSH bis-adduct, whilst that of MDA was distinctively higher. The findings of this study are supportive of a conceptual pathway that the MDI-derived biomarkers of exposure are formed through MDI-GSH adducts rather than MDA. Data from dogs support the findings from rats and show that N-acetylation does not appear to be an essential modifying factor. It is concluded that the yield of MDI-related markers of exposure is relatively low and dependent on the exposure dose (and route). MDA originating from hydrolyzed serum protein or hemoglobin appear to be confounded by false-positive background levels which are surmised to be associated with the method of hydrolysis. The determination of urinary biomarkers might be a useful tool to identify recent exposures (by any route). Due methodological uncertainties associated with the harsh hydrolysis of biological specimens may be reduced substantially when using incremental pre- to post-shift changes rather than relying solely on absolute data.

Acetanilides↗

Biomarker discovery in biological fluids.

Discovery of novel protein biomarkers is essential for successful drug discovery and development. These novel protein biomarkers may aid accelerated drug efficacy, response, or toxicity decision making based on their enhanced sensitivity and/or specificity. These biomarkers, if necessary, could eventually be converted into novel diagnostic marker assays. Proteomic platforms developed over the past few years have given us the ability to rapidly identify novel protein biomarkers in various biological matrices from cell cultures (lysates, supernatants) to human clinical samples (serum, plasma, and urine). In this article, we delineate an approach to biomarker discovery. This approach is divided into three steps, (i) identification of markers, (ii) prioritization of identified markers, and (iii) preliminary validation (qualification) of prioritized markers. Using drug-induced idiosyncratic hepatotoxicity as a case study, the article elaborates methods and techniques utilized during the three steps of biomarker discovery process. The first step involves identification of markers using multi-dimensional protein identification technology. The second step involves prioritization of a subset of marker candidates based on several criteria such as availability of reagent set for assay development and literature association to disease biology. The last step of biomarker discovery involves development of preliminary assays to confirm the bio-analytical measurements from the first step, as well as qualify the marker(s) in pre-clinical models, to initiate future marker validation and development.

14-3-3 Proteins↗

Perspective: a program to improve protein biomarker discovery for cancer.

Biomarkers for cancer risk, early detection, prognosis, and therapeutic response promise to revolutionize cancer management. Protein biomarkers offer tremendous potential in this regard due to their great diversity and intimate involvement in physiology. An effective program to discover protein biomarkers using existing technology will require team science, an integrated informatics platform, identification and quantitation of candidate biomarkers in disease tissue, mouse models of disease, standardized reagents for analyzing candidate biomarkers in bodily fluids, and implementation of automation. Technology improvements for better fractionation of the proteome, selection of specific biomarkers from complex mixtures, and multiplexed assay of biomarkers would greatly enhance progress.

Animals↗

Blood-based biomarkers of Alzheimer's disease and neurodegeneration in an indigenous African cohort using both Simoa and NULISA platforms.

In low- and middle-income countries, Alzheimer's disease (AD) constitutes a growing public health burden. However, AD biomarkers research remains underrepresented in African populations. This study assesses core biomarkers of AD and their relevance in the African context as potential aid in clinical diagnosis. Nigerian older adults from VALIANT cohort (n&#x2009;=&#x2009;967) underwent biomarker quantification in plasma (p-tau217, GFAP, NfL, A&#x3b2;42 and A&#x3b2;40) employing both the Single Molecule Assay (Simoa, Quanterix) and Nucleic acid-Linked Immuno-Sandwich Assay (NULISA, Alamar). Biomarkers were associated with disease severity in clinical-diagnostic and clinical-biological groups, with stepwise increases of p-tau217, NfL and GFAP from cognitively unimpaired to dementia (p&#x2009;<&#x2009;0.05). Results were consistent across platforms. Comparison between sexes showed higher biomarker levels in male participants across diagnostic groups. A significant effect of apoE-E4 proteotype on p-tau217 levels, after adjusting for age and sex was identified. These findings support the application of plasma AD biomarkers in the African context and the relevance of further AD biomarker research in diverse populations.

Biomarkers↗

Quantitative screening of protein biomarkers of early glycation, advanced glycation, oxidation and nitrosation in cellular and extracellular proteins by tandem mass spectrometry multiple reaction monitoring.

Glycation of proteins forms fructosamines and AGEs (advanced glycation end products). Oxidative and nitrosative stress leads to the formation of oxidative and nitrosative modifications. The modified amino acid residues formed in these processes are biomarkers of protein damage: some are risk markers and some may be risk factors for disease development. We developed a method for the concurrent quantitative measurement of 16 biomarkers indicative of protein glycation, oxidation and nitrosation damage using LC-MS/MS (LC with tandem MS detection). Underivatized analytes were detected free in physiological fluids and in enzymatic hydrolysates of cellular and extracellular proteins. Hydroimidazolones were the most important glycation biomarkers, and methionine sulphoxide was the most important oxidative biomarker quantitatively; 3-nitrotyrosine was the biomarker of nitrosation. Quantitative screening showed high levels of AGEs in cellular protein and moderate levels in protein of blood plasma. Levels of 3-nitrotyrosine were typically 100-fold lower than this. The major glycation adducts in blood plasma had high renal clearances in normal healthy human subjects, whereas methionine sulphoxide and 3-nitrotyrosine had low renal clearances due to further metabolism. Physiological AGEs in blood plasma were eliminated from the circulation in the kidney and not in the liver. LC-MS/MS peptide mapping was also used to locate the protein biomarkers. These studies reveal that advanced glycation is a significant modification of cellular and extracellular protein. The enzymatic defences against glycation, antioxidants and proteasomal protein degradation inside cells are probable factors regulating biomarker levels of cellular protein.

Biomarkers↗

Multiple biomarkers for the prediction of first major cardiovascular events and death.

BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS: For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.

Biomarkers↗

Research strategies and the use of nutrient biomarkers in studies of diet and chronic disease.

OBJECTIVE: To provide an account of the state of diet and chronic disease research designs and methods; to discuss the role and potential of aggregate and analytical observational studies and randomised controlled intervention trials; and to propose strategies for strengthening each type of study, with particular emphasis on the use of nutrient biomarkers in cohort study settings. DESIGN: Observations from diet and disease studies conducted over the past 25 years are used to identify the strengths and weaknesses of various study designs that have been used to associate nutrient consumption with chronic disease risk. It is argued that a varied research programme, employing multiple study designs, is needed in response to the widely different biases and constraints that attend aggregate and analytical epidemiological studies and controlled intervention trials. Study design modifications are considered that may be able to enhance the reliability of aggregate and analytical nutritional epidemiological studies. Specifically, the potential of nutrient biomarker measurements that provide an objective assessment of nutrient consumption to enhance analytical study reliability is emphasised. A statistical model for combining nutrient biomarker data with self-report nutrient consumption estimates is described, and related ongoing work on odds ratio parameter estimation is outlined briefly. Finally, a recently completed nutritional biomarker study among 102 postmenopausal women in Seattle is mentioned. The statistical model will be applied to biomarker data on energy expenditure, urinary nitrogen, selected blood fatty acid measurements and various blood micronutrient concentrations, and food frequency self-report data, to identify study subject characteristics, such as body mass, age or socio-economic status, that may be associated with the measurement properties of food frequency nutrient consumption estimates. This information will be crucial for the design of a potential larger nutrient biomarker study within the cohort study component of the Women's Health Initiative. SETTING AND SUBJECTS: The methodology under study is expected to be pertinent to a wide variety of diet and chronic disease association studies in the general population. Ongoing work focuses on statistical methods developed using computer simulations motivated by studies of dietary fat in relation to breast and colon cancer among post-menopausal women, and ongoing pilot studies to be described in detail elsewhere, involving post-menopausal women living in the Seattle area. RESULTS AND CONCLUSION: A varied research programme appears to be needed to make progress in the challenging diet and chronic disease research area. Such progress may include aggregate studies of diet and chronic disease that include sample surveys in diverse population groups world-wide, analytical epidemiological studies that use nutrient biomarker data to calibrate self-report nutrient consumption estimates, and randomised controlled intervention trials that arise from an enhanced infrastructure for intervention development. New innovative designs, models and methodologies are needed for each such research setting.

Aged↗

Biomarkers of effect in toads and frogs.

Amphibians are good bioindicators of environmental pollution due to their susceptibility to chemicals during their freshwater cycles. The effects of environmental pollution, together with changes in human activity and climate, have contributed to the reduction in the amphibian population over recent decades. However, toxicological research on amphibians has been rather scarce compared with that on other vertebrates. In this article we review the biochemical alterations underlying xenobiotic action and/or the detoxifying responses described for anuran species, with the aim of establishing possible biomarkers of effect. During the embryonic development of anurans, morphological and behavioural alterations are the effects most frequently cited in connection with chemical exposures. However, such biomarkers have a low sensitivity and are unspecific compared with biochemical alterations. Some primary pesticide targets, in particular cholinesterases for organophosphates and carbamates, have been evaluated. Esterases change seasonally and with the stage of development, and their sensitivity to anticholinesterase agents varies between species. Thus their use as biomarkers in anurans must be carefully analysed. Enzymes and endogenous compounds related to oxidative metabolism may also be used as biomarkers of effect. Glutathione pool, glutathione-S-transferases and metallothioneins respond in different ways to pesticides and heavy metals in anuran embryos and tadpoles. Mixed-function oxidases, in turn, are less developed in amphibians, and show a reduced induction in response to pesticide exposures. Endogenous polyamine levels are also proposed as good age-related biomarkers of damage. Finally, molecular biomarkers related to receptor binding, signal transduction and genetic response have gained increasing relevance, as they have been implicated in the fertilisation process and the earliest events in anuran development. The identification of transcription factors associated with the exposure of amphibians to xenobiotics as well as other alterations in hormone signalling appears highly promising. However, these techniques are likely to complement other methods. In conclusion, the use of several biomarkers with multiple endpoints is needed to link exposure to response and to provide better predictive tools for the environmental protection of endangered anuran species.

Animals↗

Evaluation of urinary 1-hydroxypyrene, S-phenylmercapturic acid, trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2'-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke.

The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose-response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.

8-Hydroxy-2'-Deoxyguanosine↗

Biomarkers in cancer screening, research and detection: present and future: a review.

Biomarkers provide a powerful and dynamic approach to understanding the spectrum of malignancies with applications in observational and analytic epidemiology, randomized clinical trials, screening, diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer a means for homogeneous classification of a disease and risk factor, and they can extend one's basic information about the underlying pathogenesis of disease. The goals in cancer research include finding biomarkers that can be used for the early detection of cancers, design individual therapies, and to identify underlying processes involved in the disease. Because so many myriad processes are involved in the diseased states, the goal is similar to 'finding a needle in a haystack'. However, the development of many -omic technologies, such as genomics and proteomics, has allowed us to monitor a large number of key cellular pathways simultaneously. This has enabled the identification of biomarkers and signalling molecules associated with cell growth, cell death and cellular metabolism. These are also facilitating in monitoring the functional disturbance, molecular and cellular damage, and damage response. This brief review describes the development of biomarkers in cancer research and detection with emphasis on different proteomic tools for the identification and discovery of new biomarkers, different clinical assays to detect various biomarkers in different specimens, role of biomarkers in cancer screening and last but not the least, the challenges in this direction of cancer research.

Biomarkers, Tumor↗

Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin D, C-reactive protein and fructosamine in two Dutch cohorts.

Biomarkers are widely used in epidemiology, yet there are few reliability studies to assess the appropriateness of using these biomarkers for the assessment of exposure-disease relationships. The aim of the study was to assess the reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht and Bilthoven) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total iron, total iron-binding capacity, transferrin saturation, transferrin, C-reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid, creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma, protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were analysed from the blood samples at the two points of time. For all biomarkers, except C-reactive protein, there were no substantial changes in the mean levels over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels consistently showed the highest reliability for men and women (intra-class correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and protein thiol oxidation had poor reliability; and among men iron-related biomarkers (except serum ferritin) had poor reliability. With the exception of a few gender-specific differences, most of the 20 biomarkers performed well and can be considered to have sufficient reliability to be used in future cohort studies.

Biomarkers↗

Biomarkers to assess the utility of potential reduced exposure tobacco products.

To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of exposure or toxicity and ultimately may serve as indicators for future disease risk. Recommendations were based on the relationship of the biomarker to what is known about mechanisms of tobacco-related pathogenesis, the extent to which the biomarker differs among smokers and nonsmokers, and the sensitivity of the biomarker to changes in smoking status. Other promising biomarkers were discussed. No existing biomarkers have been demonstrated to be predictive of tobacco-related disease, which highlights the importance and urgency of conducting research in this area.

Biomarkers↗

Biomarkers to assess the utility of potential reduced exposure tobacco products.

To date, we have no valid biomarkers that serve as proxies for tobacco-related disease to test potential reduced exposure products. This paper represents the deliberations of four workgroups that focused on four tobacco-related heath outcomes: Cancer, nonmalignant pulmonary disease, cardiovascular disease, and fetal toxicity. The goal of these workgroups was to identify biomarkers that offer some promise as measures of exposure or toxicity and ultimately may serve as indicators for future disease risk. Recommendations were based on the relationship of the biomarker to what is known about mechanisms of tobacco-related pathogenesis, the extent to which the biomarker differs among smokers and nonsmokers, and the sensitivity of the biomarker to changes in smoking status. Other promising biomarkers were discussed. No existing biomarkers have been demonstrated to be predictive of tobacco-related disease, which highlights the importance and urgency of conducting research in this area.

Biomarkers↗