1 4025 142 LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: NEEDS AND OPPORTUNITIES FOR INTEGRATED RESEARCH. LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ARE LEADING CAUSES OF MORBIDITY AND MORTALITY IN THE UNITED STATES AND WORLDWIDE. THEY SHARE A COMMON ENVIRONMENTAL RISK FACTOR IN CIGARETTE SMOKE EXPOSURE AND A GENETIC PREDISPOSITION REPRESENTED BY THE INCIDENCE OF THESE DISEASES IN ONLY A FRACTION OF SMOKERS. THE PRESENCE OF COPD INCREASES THE RISK OF LUNG CANCER UP TO 4.5-FOLD. TO INVESTIGATE COMMONALITIES IN DISEASE MECHANISMS AND PERSPECTIVES FOR DISEASE CHEMOPREVENTION, THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) AND THE NATIONAL CANCER INSTITUTE (NCI) HELD A WORKSHOP. THE PARTICIPANTS IDENTIFIED FOUR RESEARCH OBJECTIVES: 1) CLARIFY COMMON EPIDEMIOLOGICAL CHARACTERISTICS OF LUNG CANCER AND COPD; 2) IDENTIFY SHARED GENETIC AND EPIGENETIC RISK FACTORS; 3) IDENTIFY AND VALIDATE BIOMARKERS, MOLECULAR SIGNATURES, AND IMAGING-DERIVED MEASUREMENTS OF EACH DISEASE; AND 4) DETERMINE COMMON AND DISPARATE PATHOGENETIC MECHANISMS. THESE OBJECTIVES SHOULD BE REACHED VIA FOUR RESEARCH APPROACHES: 1) IDENTIFY, PUBLICIZE, AND ENABLE THE EVALUATION AND ANALYSIS OF EXISTING DATASETS AND REPOSITORIES OF BIOSPECIMENS; 2) OBTAIN PHENOTYPIC AND OUTCOME DATA AND BIOSPECIMENS FROM LARGE STUDIES OF SUBJECTS WITH AND/OR AT RISK FOR COPD AND LUNG CANCER; 3) DEVELOP AND USE ANIMAL AND OTHER PRECLINICAL MODELS TO INVESTIGATE PATHOGENETIC LINKS BETWEEN THE DISEASES; AND 4) CONDUCT EARLY-PHASE CLINICAL TRIALS OF POTENTIAL CHEMOPREVENTIVE AGENTS. TO FOSTER MUCH NEEDED RESEARCH INTERACTIONS, TWO FINAL RECOMMENDATIONS WERE MADE BY THE PARTICIPANTS: 1) INCORPORATE BASELINE PHENOTYPING AND OUTCOME MEASURES FOR BOTH DISEASES IN FUTURE LONGITUDINAL STUDIES OF EACH DISEASE AND 2) EXPAND COLLABORATIVE EFFORTS BETWEEN THE NCI AND NHLBI. 2009 2 3631 37 INCORPORATING BIOMARKERS IN COPD MANAGEMENT: THE RESEARCH KEEPS GOING. GLOBALLY, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) REMAINS A MAJOR CAUSE OF MORBIDITY AND MORTALITY, HAVING A SIGNIFICANT SOCIOECONOMIC EFFECT. SEVERAL MOLECULAR MECHANISMS HAVE BEEN RELATED TO COPD INCLUDING CHRONIC INFLAMMATION, TELOMERE SHORTENING, AND EPIGENETIC MODIFICATIONS. NOWADAYS, THERE IS AN INCREASING NEED FOR NOVEL THERAPEUTIC APPROACHES FOR THE MANAGEMENT OF COPD. THESE TREATMENT STRATEGIES SHOULD BE BASED ON FINDING THE SOURCE OF ACUTE EXACERBATION OF COPD EPISODES AND ESTIMATING THE PATIENT'S OWN RISK. THE USE OF BIOMARKERS AND THE MEASUREMENT OF THEIR LEVELS IN CONJUNCTION WITH COPD EXACERBATION RISK AND DISEASE PROGNOSIS IS CONSIDERED AN ENCOURAGING APPROACH. MANY TYPES OF COPD BIOMARKERS HAVE BEEN IDENTIFIED WHICH INCLUDE BLOOD PROTEIN BIOMARKERS, CELLULAR BIOMARKERS, AND PROTEASE ENZYMES. THEY HAVE BEEN ISOLATED FROM DIFFERENT SOURCES INCLUDING PERIPHERAL BLOOD, SPUTUM, BRONCHOALVEOLAR FLUID, EXHALED AIR, AND GENETIC MATERIAL. HOWEVER, THERE IS STILL NOT AN EXCLUSIVE BIOMARKER THAT IS USED FOR THE EVALUATION OF COPD BUT RATHER A COMBINATION OF THEM, AND THIS IS ATTRIBUTED TO DISEASE COMPLEXITY. IN THIS REVIEW, WE SUMMARIZE THE CLINICAL SIGNIFICANCE OF COPD-RELATED BIOMARKERS, THEIR ASSOCIATION WITH DISEASE OUTCOMES, AND COPD PATIENTS' MANAGEMENT. FINALLY, WE DEPICT THE VARIOUS SAMPLES THAT ARE USED FOR IDENTIFYING AND MEASURING THESE BIOMARKERS. 2022 3 4112 38 MECHANISMS CONTRIBUTING TO THE COMORBIDITY OF COPD AND LUNG CANCER. LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) OFTEN CO-OCCUR, AND INDIVIDUALS WITH COPD ARE AT A HIGHER RISK OF DEVELOPING LUNG CANCER. WHILE THE UNDERLYING MECHANISM FOR THIS RISK IS NOT WELL UNDERSTOOD, ITS MAJOR CONTRIBUTING FACTORS HAVE BEEN PROPOSED TO INCLUDE GENOMIC, IMMUNE, AND MICROENVIRONMENT DYSREGULATION. HERE, WE REVIEW THE EVIDENCE AND SIGNIFICANT STUDIES THAT EXPLORE THE MECHANISMS UNDERLYING THE HEIGHTENED LUNG CANCER RISK IN PEOPLE WITH COPD. GENETIC AND EPIGENETIC CHANGES, AS WELL AS THE ABERRANT EXPRESSION OF NON-CODING RNAS, PREDISPOSE THE LUNG EPITHELIUM TO CARCINOGENESIS BY ALTERING THE EXPRESSION OF CANCER- AND IMMUNE-RELATED GENES. OXIDATIVE STRESS GENERATED BY TOBACCO SMOKING PLAYS A ROLE IN REDUCING GENOMIC INTEGRITY, PROMOTING EPITHELIAL-MESENCHYMAL-TRANSITION, AND GENERATING A CHRONIC INFLAMMATORY ENVIRONMENT. THIS LEADS TO ABNORMAL IMMUNE RESPONSES THAT PROMOTE CANCER DEVELOPMENT, THOUGH NOT ALL SMOKERS DEVELOP LUNG CANCER. SEX DIFFERENCES IN THE METABOLISM OF TOBACCO SMOKE PREDISPOSE FEMALES TO DEVELOPING COPD AND ACCUMULATING DAMAGE FROM OXIDATIVE STRESS THAT POSES A RISK FOR THE DEVELOPMENT OF LUNG CANCER. DYSREGULATION OF THE LUNG MICROENVIRONMENT AND MICROBIOME CONTRIBUTES TO CHRONIC INFLAMMATION, WHICH IS OBSERVED IN COPD AND KNOWN TO FACILITATE CANCER INITIATION IN VARIOUS TUMOR TYPES. FURTHER, THERE IS A NEED TO BETTER CHARACTERIZE AND IDENTIFY THE PROPORTION OF INDIVIDUALS WITH COPD WHO ARE AT A HIGH RISK FOR DEVELOPING LUNG CANCER. WE EVALUATE POSSIBLE NOVEL AND INDIVIDUALIZED SCREENING STRATEGIES, INCLUDING BIOMARKERS IDENTIFIED IN GENETIC STUDIES AND EXHALED BREATH CONDENSATE ANALYSIS. WE ALSO DISCUSS THE USE OF CORTICOSTEROIDS AND STATINS AS CHEMOPREVENTIVE AGENTS TO PREVENT LUNG CANCER. IT IS CRUCIAL THAT WE OPTIMIZE THE CURRENT METHODS FOR THE EARLY DETECTION AND MANAGEMENT OF LUNG CANCER AND COPD IN ORDER TO IMPROVE THE HEALTH OUTCOMES FOR A LARGE AFFECTED POPULATION. 2023 4 6783 31 [CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN WOMEN]. FOR THE PAST SEVERAL YEARS THE NUMBER OF WOMEN SUFFERING FROM CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS BEEN STEADILY INCREASING. THIS FACT PROMPTS THE DEBATE WHICH FACTORS, IN ADDITION TO CONSIDERABLY INCREASING PREVALENCE OF CIGARETTE SMOKING AMONG YOUNG WOMEN, ARE RESPONSIBLE FOR THESE EPIDEMIOLOGIC CHANGES. DIFFERENCES IN THE NATURAL HISTORY AND PROGNOSIS OF COPD IN FEMALES AND MALES ARE PRESENTED IN THE PAPER, AS WELL AS THE NUMBER OF POTENTIAL ETHIOPATHOGENETIC AND PATHOPHYSIOLOGIC FACTORS INFLUENCING THESE VARIATIONS. AMONG THEM, DIFFERENCES IN THE COPD RISK FACTORS SPECTRUM IN BOTH GENDERS AND IN AIRWAYS ANATOMY ARE POINTED OUT, AND THE MECHANISMS RESPONSIBLE FOR GREATER WOMEN'S SUSCEPTIBILITY TO COMPONENTS OF CIGARETTE SMOKE, WHICH REFLECT GENETIC (ENZYME POLYMORPHISMS), EPIGENETIC (DIMINISHED DNA METHYLATION) AND HORMONAL (ESTROGENS) INFLUENCES ON XENOBIOTICS METABOLISM. FURTHER, SEX-RELATED DIFFERENCES REGARDING COPD PHENOTYPES (CHRONIC BRONCHITIS VS. EMPHYSEMA), IMMUNOLOGICAL MARKERS AND CLINICAL MANIFESTATION OF DISEASE ARE UNDERLINED IN THE PAPER. MORE FREQUENT COEXISTENCE OF ANXIETY AND DEPRESSION, COPD EXACERBATIONS AND WORSE QUALITY OF LIFE IN WOMEN ARE ALSO EMPHASIZED. OTHER DIFFERENCES, POINTED OUT BY AUTHORS INCLUDE AUTOIMMUNOLOGICAL CONCEPTION OF PATHOGENESIS OF COPD (GREATER FEMALE SUSCEPTIBILITY TO PRODUCE AUTOANTIBODIES), RISK FACTORS OF DISEASE EXACERBATION AND, AT LAST, RESPONSE TO CERTAIN FORMS OF COPD TREATMENT (NICOTINE REPLACEMENT THERAPY, LONG-TERM OXYGEN THERAPY). 2012 5 3027 33 GENETICS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMPLEX DISEASE WITH MULTIFACTORIAL BACKGROUND, BASED ON THE INTERACTION OF ENVIRONMENTAL AND GENETIC FACTORS. ENVIRONMENTAL FACTORS ARE CLEARLY RELATED TO THE DEVELOPMENT OF THE DISEASE. HOWEVER, FAMILY AND TWIN STUDIES SUGGESTED GENETICS FACTORS TO BE ONE OF THE IMPORTANT DETERMINANTS FOR THE DEVELOPMENT OF COPD. DIFFERENT APPROACHES HAVE BEEN USED TO IDENTIFY GENES OF INTEREST. GENOMEWIDE LINKAGE ANALYSIS FOUND AREAS OF INTEREST ON DIFFERENT CHROMOSOMES, WITH SOME GENES LOCATED IN THIS REGIONS BEING IDENTIFIED AND REPLICATED AS SUSCEPTIBILITY GENES. NUMEROUS OF CANDIDATE GENES THAT COULD BE LINKED TO DISEASE PATHOGENESIS HAVE BEEN IMPLICATED IN COPD GENETICS. HOWEVER, THE CANDIDATE GENE APPROACH IS OFTEN LIMITED BY INCONSISTENT RESULTS IN OTHER STUDY POPULATIONS. RECENTLY, A COMBINATION OF DIFFERENT METHODS IS USED GIVING MORE EVIDENCE FOR SOME CANDIDATE GENES, INCLUDING TGFBETA-1, SURFACTANT, SERPINE2 AND MICROSOMAL EPOXIDE HYDROLASE. IN THE FUTURE ONGOING EXACT PHENOTYPE DEFINITION, COMBINATION OF SEVERAL APPROACHES, GENOME-WIDE ASSOCIATION STUDIES AND ANIMAL MODEL GENETICS WILL LEAD TO NEW INSIGHTS INTO THE GENETICS OF COPD, WITH EPIGENETIC FACTORS NEEDS TO BE FURTHER INVESTIGATED AND CONSIDERED IN CONCERT WITH GENETIC FINDINGS. 2007 6 6788 40 [COPD AND LUNG CANCER: EPIDEMIOLOGICAL AND BIOLOGICAL LINKS]. LUNG CANCER AND CHRONIC OBSTRUCTIVE LUNG DISEASE (COPD) ARE TWO COMMON FATAL DISEASES. APART FROM THEIR COMMON LINK TO TOBACCO, THESE TWO DISEASES ARE USUALLY CONSIDERED TO BE THE RESULT OF SEPARATE DISTINCT MECHANISMS. IN THE PAST 15 YEARS, NUMEROUS STUDIES HAVE PRODUCED ARGUMENTS IN FAVOUR OF A RELATIONSHIP BETWEEN THESE TWO PATHOLOGIES THAT GOES BEYOND A SIMPLE ADDITION OF RISK FACTORS. AT THE EPIDEMIOLOGICAL LEVEL, THERE ARE DATA THAT DEMONSTRATE AN INCREASED INCIDENCE OF BRONCHIAL CARCINOMA IN PATIENTS WITH COPD. THE LINKS BETWEEN THESE TWO PATHOLOGIES ARE STILL UNEXPLAINED BUT THERE ARE NUMEROUS ARGUMENTS SUPPORTING A COMMON PHYSIOPATHOLOGY. COMMON GENETIC AND EPIGENETIC ABNORMALITIES, MECHANICAL FACTORS AND SIGNALISATION PATHWAYS HAVE BEEN QUOTED. COPD AND LUNG CANCER APPEAR TO BE TWO DISEASES POSSESSING A GENETIC BASIS THAT CREATES A PREDISPOSITION TO ENVIRONMENTAL OR TOXIC ASSAULTS, RESULTING IN A DIFFERENT CLINICAL MANIFESTATION IN EACH DISEASE. CONSEQUENTLY, IMPROVEMENTS IN THE MANAGEMENT OF THESE TWO DISEASES WILL INVOLVE A MORE INTENSIVE INVESTIGATION OF THEIR PHYSIOPATHOLOGY, AND REQUIRE A CLOSER COLLABORATION BETWEEN RESEARCH CENTRES AND CLINICAL UNITS. 2012 7 396 33 AN UPDATE ON EPIGENETICS AND CHILDHOOD RESPIRATORY DISEASES. EPIGENETIC MECHANISMS, DEFINED AS CHANGES IN PHENOTYPE OR GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE, HAVE BEEN PROPOSED TO CONSTITUTE A LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT AFFECT COMPLEX DISEASES. RECENT STUDIES SHOW THAT DNA METHYLATION, ONE OF THE KEY EPIGENETIC MECHANISMS, IS ALTERED IN CHILDREN EXPOSED TO AIR POLLUTANTS AND ENVIRONMENTAL TOBACCO SMOKE EARLY IN LIFE. SEVERAL CANDIDATE GENE STUDIES ON EPIGENETICS HAVE BEEN PUBLISHED TO DATE, BUT IT IS ONLY RECENTLY THAT GLOBAL METHYLATION ANALYSES HAVE BEEN PERFORMED FOR RESPIRATORY DISORDERS SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, LARGE-SCALE STUDIES WITH ADEQUATE POWER ARE YET TO BE PRESENTED IN CHILDREN, AND IMPLICATIONS FOR CLINICAL USE REMAIN TO BE EVALUATED. IN THIS REVIEW, WE SUMMARIZE THE RECENT ADVANCES IN EPIGENETICS AND RESPIRATORY DISORDERS IN CHILDREN, WITH A MAIN FOCUS ON METHODOLOGICAL CHALLENGES AND ANALYSES RELATED TO PHENOTYPE AND EXPOSURE USING GLOBAL METHYLATION APPROACHES. 2014 8 3028 27 GENETICS OF COMPLEX AIRWAY DISEASE. THE PAST 3 YEARS HAVE SEEN HIGHLY SIGNIFICANT GENETIC EFFECTS IDENTIFIED FOR A WIDE VARIETY OF COMMON COMPLEX DISEASES, INCLUDING THE AIRWAY DISORDERS OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. IT APPEARS THAT ONLY A PORTION OF THE GENETICALLY MEDIATED SUSCEPTIBILITY TO COMPLEX DISEASES HAS BEEN IDENTIFIED, AND THERE IS MUCH LEFT TO BE DISCOVERED. THIS REVIEW BRIEFLY DESCRIBES THE RESULTS OF THE GENOME-WIDE ASSOCIATION STUDIES OF ASTHMA AND GIVES AN OVERVIEW OF THE PARALLEL AND INCREASINGLY LARGE-SCALE STUDIES THAT ARE TAKING PLACE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE FUTURE IMPACT IS DISCUSSED OF TECHNOLOGICAL ADVANCES THAT ALLOW INCREASINGLY LARGE-SCALE GENE EXPRESSION STUDIES, NEXT-GENERATION SEQUENCING, AND GENOME-WIDE TESTING FOR EPIGENETIC EFFECTS. THE USE OF GENETIC TECHNOLOGY TO EXAMINE THE AIRWAY MICROBIOTA THAT INTERACT WITH THE MUCOSA IN HEALTH AND DISEASE IS DESCRIBED. 2011 9 3100 35 GENOMIC IMPACT OF CIGARETTE SMOKE, WITH APPLICATION TO THREE SMOKING-RELATED DISEASES. THERE IS CONSIDERABLE EVIDENCE THAT INHALED TOXICANTS SUCH AS CIGARETTE SMOKE CAN CAUSE BOTH IRREVERSIBLE CHANGES TO THE GENETIC MATERIAL (DNA MUTATIONS) AND PUTATIVELY REVERSIBLE CHANGES TO THE EPIGENETIC LANDSCAPE (CHANGES IN THE DNA METHYLATION AND CHROMATIN MODIFICATION STATE). THE DISEASES THAT ARE BELIEVED TO INVOLVE GENETIC AND EPIGENETIC PERTURBATIONS INCLUDE LUNG CANCER, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), AND CARDIOVASCULAR DISEASE (CVD), ALL OF WHICH ARE STRONGLY LINKED EPIDEMIOLOGICALLY TO CIGARETTE SMOKING. IN THIS REVIEW, WE HIGHLIGHT THE SIGNIFICANCE OF GENOMICS AND EPIGENOMICS IN THESE MAJOR SMOKING-RELATED DISEASES. WE ALSO SUMMARIZE THE IN VITRO AND IN VIVO FINDINGS ON THE SPECIFIC PERTURBATIONS THAT SMOKE AND ITS CONSTITUENT COMPOUNDS CAN INFLICT UPON THE GENOME, PARTICULARLY ON THE PULMONARY SYSTEM. FINALLY, WE REVIEW STATE-OF-THE-ART GENOMICS AND NEW TECHNIQUES SUCH AS HIGH-THROUGHPUT SEQUENCING AND GENOME-WIDE CHROMATIN ASSAYS, RAPIDLY EVOLVING TECHNIQUES WHICH HAVE ALLOWED EPIGENETIC CHANGES TO BE CHARACTERIZED AT THE GENOME LEVEL. THESE TECHNIQUES HAVE THE POTENTIAL TO SIGNIFICANTLY IMPROVE OUR UNDERSTANDING OF THE SPECIFIC MECHANISMS BY WHICH EXPOSURE TO ENVIRONMENTAL CHEMICALS CAUSES DISEASE. SUCH MECHANISTIC KNOWLEDGE PROVIDES A VARIETY OF OPPORTUNITIES FOR ENHANCED PRODUCT SAFETY ASSESSMENT AND THE DISCOVERY OF NOVEL THERAPEUTIC INTERVENTIONS. 2012 10 629 35 BIOLOGICAL AND GENETIC MECHANISMS OF COPD, ITS DIAGNOSIS, TREATMENT, AND RELATIONSHIP WITH LUNG CANCER. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS ONE OF THE MOST PREVALENT CHRONIC ADULT DISEASES, WITH SIGNIFICANT WORLDWIDE MORBIDITY AND MORTALITY. ALTHOUGH LONG-TERM TOBACCO SMOKING IS A CRITICAL RISK FACTOR FOR THIS GLOBAL HEALTH PROBLEM, ITS MOLECULAR MECHANISMS REMAIN UNCLEAR. SEVERAL PHENOMENA ARE THOUGHT TO BE INVOLVED IN THE EVOLUTION OF EMPHYSEMA, INCLUDING AIRWAY INFLAMMATION, PROTEINASE/ANTI-PROTEINASE IMBALANCE, OXIDATIVE STRESS, AND GENETIC/EPIGENETIC MODIFICATIONS. FURTHERMORE, COPD IS ONE MAIN RISK FOR LUNG CANCER (LC), THE DEADLIEST FORM OF HUMAN TUMOR; FORMATION AND CHRONIC INFLAMMATION ACCOMPANYING COPD CAN BE A POTENTIAL DRIVER OF MALIGNANCY MATURATION (0.8-1.7% OF COPD CASES DEVELOP CANCER/PER YEAR). RECENTLY, THE DEVELOPMENT OF MORE RESEARCH BASED ON COPD AND LUNG CANCER MOLECULAR ANALYSIS HAS PROVIDED NEW LIGHT FOR UNDERSTANDING THEIR PATHOGENESIS, IMPROVING THE DIAGNOSIS AND TREATMENTS, AND ELUCIDATING MANY CONNECTIONS BETWEEN THESE DISEASES. OUR REVIEW EMPHASIZES THE BIOLOGICAL FACTORS INVOLVED IN COPD AND LUNG CANCER, THE ADVANCES IN THEIR MOLECULAR MECHANISMS' RESEARCH, AND THE STATE OF THE ART OF DIAGNOSIS AND TREATMENTS. THIS WORK COMBINES MANY BIOLOGICAL AND GENETIC ELEMENTS INTO A SINGLE WHOLE AND STRONGLY LINKS COPD WITH LUNG TUMOR FEATURES. 2023 11 5787 40 SPUTUM ANALYSIS: NON-INVASIVE EARLY LUNG CANCER DETECTION. LUNG CANCER IS THE LEADING CAUSE OF CANCER-RELATED DEATHS OVER THE WORLD, CHARACTERIZED BY A VERY HIGH MORTALITY RATE. MOLECULAR TECHNIQUE DEVELOPMENT TRIES TO FOCUS ON EARLY DETECTION OF CANCERS BY STUDYING MOLECULAR ALTERATIONS THAT CHARACTERIZE CANCER CELLS. WORLDWIDE LUNG CANCER RESEARCH HAS FOCUSED ON AN EVER-INCREASING NUMBER OF MOLECULAR ELEMENTS OF CARCINOGENESIS AT GENETIC, EPIGENETIC AND PROTEIN LEVELS. THE NON-INVASIVENESS IS THE CHARACTERISTIC THAT ALL CLINICAL TRIALS ON CANCER DETECTION SHOULD HAVE. ABNORMAL CHEST IMAGING AND/OR NON-SPECIFIC SYMPTOMS ARE INITIAL SIGNALS OF LUNG CANCER THAT APPEAR IN AN ADVANCED STAGE OF DISEASE. THIS FACT REPRESENTS THE CAUSE OF THE LOW 5-YEAR SURVIVAL RATE: OVER 90% OF PATIENTS DYING WITHIN 5 YEARS OF DIAGNOSIS. SINCE SMOKERS HAVE HIGHER QUANTITY OF SPUTUM CONTAINING EXFOLIATED CELLS FROM THE BRONCHIAL TREE, AND THE SPUTUM REPRESENTS THE MOST EASILY ACCESSIBLE BIOLOGICAL FLUID AND ITS COLLECTION IS NON-INVASIVE, ANALYSIS OF THIS SAMPLE REPRESENTS A GOOD AREA OF RESEARCH IN EARLY LUNG CANCER DIAGNOSIS. CONTINUED CIGARETTE SMOKING IS THE CAUSE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), WITH AN ESTIMATED ATTRIBUTABLE RISK FACTOR EXCEEDING 80% IN SMOKING AFFECTED INDIVIDUALS. LUNG CANCER IS FOUND IN 40-70% OF PATIENTS WITH COPD, PARTICULARLY IN SEVERE DISEASE, AND IT IS A COMMON CAUSE OF DEATH IN THESE PATIENTS. A LARGE PROSPECTIVE TRIAL OF ALMOST HALF A MILLION NON-SMOKERS SHOWED AS LUNG CANCER IS ALSO COMMON IN PATIENTS WITH COPD WHO HAVE NEVER SMOKED. THIS REVIEW DESCRIBES ISSUES RELATED TO EARLY LUNG CANCER SCREENING USING NON-INVASIVE METHODS. 2013 12 4445 52 MOLECULAR LINKS BETWEEN COPD AND LUNG CANCER: NEW TARGETS FOR DRUG DISCOVERY? COPD AND LUNG CANCER ARE LEADING CAUSES OF MORBIDITY AND MORTALITY WORLDWIDE, AND THEY SHARE A COMMON ENVIRONMENTAL RISK FACTOR IN CIGARETTE SMOKE EXPOSURE AND A GENETIC PREDISPOSITION REPRESENTED BY THEIR INCIDENCE IN ONLY A FRACTION OF SMOKERS. THIS REFLECTS THE ABILITY OF CIGARETTE SMOKE TO INDUCE AN INFLAMMATORY RESPONSE IN THE AIRWAYS OF SUSCEPTIBLE SMOKERS. MOREOVER, COPD COULD BE A DRIVING FACTOR IN LUNG CANCER, BY INCREASING OXIDATIVE STRESS AND THE RESULTING DNA DAMAGE AND REPRESSION OF THE DNA REPAIR MECHANISMS, CHRONIC EXPOSURE TO PRO-INFLAMMATORY CYTOKINES, REPRESSION OF INNATE IMMUNITY AND INCREASED CELLULAR PROLIFERATION. AREAS COVERED: WE HAVE FOCUSED OUR REVIEW ON THE POTENTIAL PATHOGENIC MOLECULAR LINKS BETWEEN TOBACCO SMOKING-RELATED COPD AND LUNG CANCER AND THE POTENTIAL MOLECULAR TARGETS FOR NEW DRUG DEVELOPMENT BY UNDERSTANDING THE COMMON SIGNALING PATHWAYS INVOLVED IN COPD AND LUNG CANCER. EXPERT COMMENTARY: RESEARCH IN THIS FIELD IS MOSTLY LIMITED TO ANIMAL MODELS OR SMALL CLINICAL TRIALS. LARGE CLINICAL TRIALS ARE NEEDED BUT MOSTLY COMBINED MODELS OF COPD AND LUNG CANCER ARE NECESSARY TO INVESTIGATE THE PROCESSES CAUSED BY CHRONIC INFLAMMATION, INCLUDING GENETIC AND EPIGENETIC ALTERATION, AND THE EXPRESSION OF INFLAMMATORY MEDIATORS THAT LINK COPD AND LUNG CANCER, TO IDENTIFY NEW MOLECULAR THERAPEUTIC TARGETS. 2019 13 1928 40 ENVIRONMENTAL EXPOSURE MEASUREMENT IN CANCER EPIDEMIOLOGY. ENVIRONMENTAL EXPOSURES, USED IN THE BROADEST SENSE OF LIFESTYLE, INFECTIONS, RADIATION, NATURAL AND MAN-MADE CHEMICALS AND OCCUPATION, ARE A MAJOR CAUSE OF HUMAN CANCER. HOWEVER, THE PRECISE CONTRIBUTION OF SPECIFIC RISK FACTORS AND THEIR INTERACTION, BOTH WITH EACH OTHER AND WITH GENOTYPE, CONTINUES TO BE DIFFICULT TO ELUCIDATE. THIS IS PARTIALLY DUE TO LIMITATIONS IN ACCURATELY MEASURING EXPOSURE WITH THE SUBSEQUENT RISK OF MISCLASSIFICATION. ONE OF THE PRIMARY CHALLENGES OF MOLECULAR CANCER EPIDEMIOLOGY THEREFORE IS TO IMPROVE EXPOSURE ASSESSMENT. PROGRESS HAS BEEN MADE WITH BIOMARKERS SUCH AS CARCINOGENS AND THEIR METABOLITES, DNA AND PROTEIN ADDUCTS AND MUTATIONS MEASURED IN VARIOUS TISSUES AND BODY FLUIDS. NEVERTHELESS, MUCH REMAINS TO BE ACCOMPLISHED IN ORDER TO ESTABLISH AETIOLOGY AND PROVIDE THE EVIDENCE BASE FOR PUBLIC HEALTH DECISIONS. THIS REVIEW CONSIDERS SOME OF THE PRINCIPLES BEHIND THE APPLICATION OF EXPOSURE BIOMARKERS IN CANCER EPIDEMIOLOGY. IT ALSO DEMONSTRATES HOW THE SAME BIOMARKERS CAN CONTRIBUTE BOTH TO ESTABLISHING THE BIOLOGICAL PLAUSIBILITY OF ASSOCIATIONS BETWEEN EXPOSURE AND DISEASE AND BE VALUABLE ENDPOINTS IN INTERVENTION STUDIES. THE POTENTIAL OF NEW TECHNOLOGIES SUCH AS TRANSCRIPTOMICS, PROTEOMICS AND METABONOMICS TO PROVIDE A STEP CHANGE IN ENVIRONMENTAL EXPOSURE ASSESSMENT IS DISCUSSED. AN INCREASING RECOGNITION OF THE ROLE OF EPIGENETIC CHANGES IN CARCINOGENESIS PRESENTS A FRESH CHALLENGE AS ALTERATIONS IN DNA METHYLATION, HISTONE MODIFICATION AND MICRORNA IN RESPONSE TO ENVIRONMENTAL EXPOSURES DEMAND A NEW GENERATION OF EXPOSURE BIOMARKER. THE OVERALL IMPORTANCE OF THIS AREA OF RESEARCH IS BROUGHT INTO SHARP RELIEF BY THE LARGE PROSPECTIVE COHORT STUDIES (E.G. UK BIOBANK) WHICH NEED ACCURATE EXPOSURE MEASUREMENT IN ORDER TO SHED LIGHT ON THE COMPLEX GENE:ENVIRONMENT INTERACTIONS UNDERLYING COMMON CHRONIC DISORDERS INCLUDING CANCER. IT IS SUGGESTED THAT A CONCERTED EFFORT IS NOW REQUIRED, WITH APPROPRIATE FUNDING, TO DEVELOP AND VALIDATE THE REQUIRED EXPOSURE ASSESSMENT METHODOLOGY BEFORE THESE COHORTS COME TO MATURITY. 2009 14 6834 23 [IMMUNOPATHOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMMON, PREVENTABLE AND TREATABLE CONDITION THAT HAS A COMPLEX PATHOPHYSIOLOGY AND AN EVEN MORE COMPLEX IMMUNOPATHOLOGICAL PROCESS. THE PURPOSE OF THIS REVIEW WAS TO ANALYZE COPD IMMUNOPATHOLOGICAL ASPECTS, WHICH WAS ADDRESSED BY UNDERTAKING A LITERATURE SEARCH FOR THE MOST RELEVANT DOCUMENTS INDEXED IN THE PUBMED DATABASE OVER THE LAST 10 YEARS. DIFFERENT CONCLUSIONS COULD BE DRAWN: IN COPD IMMUNOPATHOLOGY THERE ARE IMMUNE AND NON-IMMUNE INFLAMMATORY CHANGES WITH OXIDATIVE STRESS IMBALANCE, THERE ARE ALTERATIONS IN THE PROTEASE/ANTI-PROTEASE RATIO CAUSED BY DIRECT AND INDIRECT GENETIC AND EPIGENETIC-ENVIRONMENTAL DEFECTS; COPD PRODUCES IRREVERSIBLE TISSUE DAMAGE AND CHRONIC INFLAMMATION WITH TISSUE REPAIR ALTERATION, WHICH INDUCES CHRONIC OBSTRUCTION OF THE AIRWAY, BRONCHITIS AND SYSTEMIC DAMAGE. MOST COMMON RESULTING COMORBIDITIES INCLUDE CARDIOVASCULAR DISEASE, METABOLIC SYNDROME, OSTEOPOROSIS, DEPRESSION, MUSCULOSKELETAL DYSFUNCTION, INCREASED BIOLOGICAL AGE, LUNG CANCER AND OTHER TYPES OF MALIGNANCIES. IN THE CONCEPTION OF COPD, RECOGNIZING THAT IT IS A NON-TRANSMITTABLE AND PREVENTABLE DISEASE IS INDISPENSABLE. 2017 15 2859 31 FROM SMOKING TO COPD--CURRENT APPROACHES. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) REMAINS A LEADING CAUSE OF DEATH ALL OVER THE WORLD. EVEN THOUGH IT IS THE MOST INTENSELY STUDIED DISEASE INDUCED BY CIGARETTE SMOKING THERE ARE STILL INCOMPLETE RESEARCHES CONCERNING ITS PATHOPHYSIOLOGY AND TREATMENT. SO FAR IT HAS BEEN DETERMINED THE DELETERIOUS EFFECTS OF THE SECRETED MOLECULES DIVERSITY AND SOME FEASIBLE THERAPIES FOR THEIR DIMINUTION. ACCORDING TO CURRENT STUDIES MORE RELEVANCE GAINS THE POSSIBLE AUTOIMMUNE ORIGIN OF COPD AND THE EPIGENETIC MODIFICATIONS. THE IDEA OF AUTOIMMUNITY IN SMOKING INDUCED COPD BEGAN TO BE SPECULATED WITH THE DISCOVERY OF AUTOANTIBODIES IN PATIENT'S SERUM, BUT THERE ARE SOME STUDIES WHO CONSIDER ANTIBODY COMPLEXES THAT RESIDE IN THE LUNG TISSUE AS MORE RELEVANT FOR FUTURE RESEARCH. BY DEVELOPING THE AUTOIMMUNE ASPECT OF COPD IT WILL BECOME POSSIBLE TO SELECT MORE PRECISE TREATMENT STRATEGIES. THE IMPORTANCE OF EPIGENETIC CHANGES IN THIS FIELD MIGHT BE APPRECIATED STARTING WITH THE FACT OF AN EXISTING CONNECTION BETWEEN EPIGENETIC MODIFICATIONS INDUCED BY MATERNAL SMOKING AND LATTER COPD DEVELOPMENT. THIS EXPLAINS THE TENDENCY TOWARD DIFFERENT DRUGS CAPABLE OF RESTORING THESE TRANSFORMATIONS SUCH AS DEACETYLATION AGENTS EXPECTED ALSO TO PREVENT STEROID RESISTANCE. NEVERTHELESS SMOKING CESSATION REMAINS AS THE INDISPENSABLE APPROACH FOR COPD TREATMENT AND PREVENTION. 2016 16 728 34 CAN WE IDENTIFY PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS PROGRESSION WHO WILL RESPOND TO TREATMENT? A FOCUS ON BIOMARKERS AND FRAILTY. OSTEOARTHRITIS (OA), A DISEASE AFFECTING DIFFERENT PATIENT PHENOTYPES, APPEARS AS AN OPTIMAL CANDIDATE FOR PERSONALIZED HEALTHCARE. THE AIM OF THE DISCUSSIONS OF THE EUROPEAN SOCIETY FOR CLINICAL AND ECONOMIC ASPECTS OF OSTEOPOROSIS AND OSTEOARTHRITIS (ESCEO) WORKING GROUP WAS TO EXPLORE THE VALUE OF MARKERS OF DIFFERENT SOURCES IN DEFINING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. THE ESCEO ORGANIZED A SERIES OF MEETINGS TO EXPLORE THE POSSIBILITY OF IDENTIFYING PATIENTS WHO WOULD MOST BENEFIT FROM TREATMENT FOR OA, ON THE BASIS OF RECENT DATA AND EXPERT OPINION. IN THE FIRST MEETING, PATIENT PHENOTYPES WERE IDENTIFIED ACCORDING TO THE NUMBER OF AFFECTED JOINTS, BIOMECHANICAL FACTORS, AND THE PRESENCE OF LESIONS IN THE SUBCHONDRAL BONE. IN THE SECOND MEETING, SUMMARIZED IN THE PRESENT ARTICLE, THE WORKING GROUP EXPLORED OTHER MARKERS INVOLVED IN OA. PROFILES OF PATIENTS MAY BE DEFINED ACCORDING TO THEIR LEVEL OF PAIN, FUNCTIONAL LIMITATION, AND PRESENCE OF COEXISTENT CHRONIC CONDITIONS INCLUDING FRAILTY STATUS. A CONSIDERABLE AMOUNT OF DATA SUGGESTS THAT MAGNETIC RESONANCE IMAGING MAY ALSO ASSIST IN DELINEATING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. AMONG MULTIPLE BIOCHEMICAL BIOMARKERS IDENTIFIED, NONE IS SUFFICIENTLY VALIDATED AND RECOGNIZED TO IDENTIFY PATIENTS WHO SHOULD BE TREATED. CONSIDERABLE EFFORTS ARE ALSO BEING MADE TO IDENTIFY GENETIC AND EPIGENETIC FACTORS INVOLVED IN OA, BUT RESULTS ARE STILL LIMITED. THE MANY POTENTIAL BIOMARKERS THAT COULD BE USED AS POTENTIAL STRATIFIERS ARE PROMISING, BUT MORE RESEARCH IS NEEDED TO CHARACTERIZE AND QUALIFY THE EXISTING BIOMARKERS AND TO IDENTIFY NEW CANDIDATES. 2015 17 1516 30 DNA METHYLATION AS A BIOMARKER OF AGING IN EPIDEMIOLOGIC STUDIES. CANCER IS LARGELY AN AGING DISEASE. ACCELERATED BIOLOGICAL AGING MAY BE THE STRONGEST PREDICTOR OF CANCER AND OTHER CHRONIC DISEASE RISKS. IN THE ABSENCE OF RELIABLE AND QUANTIFIABLE BIOMARKERS OF AGING TO DATE, IT HAS LONG BEEN OBSERVED THAT TUMORIGENESIS SHARES DISTINCT EPIGENETIC ALTERATIONS WITH THE AGING PROCESS. RECENTLY, EPIGENETIC AGE ESTIMATES HAVE BEEN DEVELOPED BASED ON THE AVAILABILITY OF GENOME-WIDE DNA METHYLATION PROFILES, BY APPLYING IN THE PREDICTION FORMULA THE METHYLATION LEVEL AT A SUBSET OF HIGHLY PREDICTIVE METHYLATION SITES, CALLED EPIGENETIC CLOCK. THESE DNA METHYLATION AGE ESTIMATES HAVE PRODUCED REMARKABLY STRONG CORRELATIONS WITH CHRONOLOGICAL AGE, WITH A SMALL DEVIATION AND HIGH REPRODUCIBILITY ACROSS DIFFERENT AGE GROUPS AND STUDY POPULATIONS. MOREOVER, AN INCREASING NUMBER OF EPIDEMIOLOGIC STUDIES HAVE DEMONSTRATED AN INDEPENDENT ASSOCIATION OF DNA METHYLATION AGE OR THE EXTENT OF ACCELERATION WITH MORTALITY AND VARIOUS AGING-RELATED CONDITIONS, EVEN AFTER ACCOUNTING FOR DIFFERENCES IN CHRONOLOGICAL AGE AND OTHER RISK FACTORS. ALTHOUGH EPIGENETIC PROFILES ARE KNOWN TO BE TISSUE-SPECIFIC, BOTH TARGET TISSUE- AND MULTIPLE TISSUE-DERIVED ESTIMATES APPEAR TO PERFORM WELL TO CAPTURE WHAT IS THOUGHT TO BE THE CUMULATIVE EPIGENETIC DRIFT THAT REPRESENTS A MULTIFACTORIAL DEGENERATIVE PROCESS ACROSS TISSUES AND ORGANISMS. FURTHER REFINEMENT OF THE EPIGENETIC AGE ESTIMATES IS ANTICIPATED OVER TIME TO ACCOMMODATE A BETTER TECHNOLOGICAL COVERAGE OF THE METHYLOME AND A BETTER UNDERSTANDING OF THE BIOLOGY UNDERLYING PREDICTIVE REGIONS. EPIDEMIOLOGIC PRINCIPLES WILL REMAIN CRITICAL FOR THE EVALUATION OF RESEARCH FINDINGS INVOLVING, FOR EXAMPLE, DIFFERENT STUDY POPULATIONS, DESIGN, FOLLOW-UP TIME, AND QUALITY OF COVARIATE DATA. OVERALL, THE EPIGENETIC AGE ESTIMATES ARE AN EXCITING DEVELOPMENT WITH USEFUL IMPLICATIONS FOR BIOMEDICAL RESEARCH OF HEALTHY AGING AND DISEASE PREVENTION AND CONTROL. 2018 18 2651 34 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 19 1188 36 COPD: A MULTIFACTORIAL SYSTEMIC DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS TRADITIONALLY BEEN CONSIDERED A DISEASE OF THE LUNGS SECONDARY TO CIGARETTE SMOKING AND CHARACTERIZED BY AIRFLOW OBSTRUCTION DUE TO ABNORMALITIES OF BOTH AIRWAY (BRONCHITIS) AND LUNG PARENCHYMA (EMPHYSEMA). IT IS NOW WELL KNOWN THAT COPD IS ASSOCIATED WITH SIGNIFICANT SYSTEMIC ABNORMALITIES, SUCH AS RENAL AND HORMONAL ABNORMALITIES, MALNUTRITION, MUSCLE WASTING, OSTEOPOROSIS, AND ANEMIA. HOWEVER, IT IS STILL UNCLEAR WHETHER THEY REPRESENT CONSEQUENCES OF THE PULMONARY DISORDER, OR WHETHER COPD SHOULD BE CONSIDERED AS A SYSTEMIC DISEASE. THESE SYSTEMIC ABNORMALITIES HAVE BEEN ATTRIBUTED TO AN INCREASED LEVEL OF SYSTEMIC INFLAMMATION. CHRONIC INFLAMMATION, HOWEVER, MAY NOT BE THE ONLY CAUSE OF THE SYSTEMIC EFFECTS OF COPD. RECENT DATA FROM HUMANS AND ANIMAL MODELS SUPPORT THE VIEW THAT EMPHYSEMA MAY BE A VASCULAR DISEASE. OTHER STUDIES HAVE HIGHLIGHTED THE ROLE OF REPAIR FAILURE, BONE MARROW ABNORMALITY, GENETIC AND EPIGENETIC FACTORS, IMMUNOLOGICAL DISORDERS AND INFECTIONS AS POTENTIAL CAUSES OF COPD SYSTEMIC MANIFESTATIONS. BASED ON THIS NEW EVIDENCE, IT IS REASONABLE TO CONSIDER COPD, AND EMPHYSEMA IN PARTICULAR, AS 'A DISEASE WITH A SIGNIFICANT SYSTEMIC COMPONENT' IF NOT A 'SYSTEMIC DISEASE' PER SE. THE AIM OF THIS REVIEW IS TO GIVE AN OVERVIEW OF THE MOST RELEVANT AND INNOVATIVE HYPOTHESIS ABOUT THE EXTRAPULMONARY MANIFESTATIONS OF COPD. 2011 20 1958 29 EPIGENETIC AGING AND COLORECTAL CANCER: STATE OF THE ART AND PERSPECTIVES FOR FUTURE RESEARCH. ALTHOUGH TRANSLATIONAL RESEARCH HAS IDENTIFIED A LARGE NUMBER OF POTENTIAL BIOMARKERS INVOLVED IN COLORECTAL CANCER (CRC) CARCINOGENESIS, A BETTER UNDERSTANDING OF THE MOLECULAR PATHWAYS ASSOCIATED WITH BIOLOGICAL AGING IN COLORECTAL CELLS AND TISSUES IS NEEDED. HERE, WE AIM TO SUMMARIZE THE STATE OF THE ART ABOUT THE ROLE OF AGE ACCELERATION, DEFINED AS THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, IN THE DEVELOPMENT AND PROGRESSION OF CRC. SOME STUDIES HAVE SHOWN THAT ACCELERATED BIOLOGICAL AGING IS POSITIVELY ASSOCIATED WITH THE RISK OF CANCER AND DEATH IN GENERAL. IN LINE WITH THESE FINDINGS, OTHER STUDIES HAVE SHOWN HOW THE ASSESSMENT OF EPIGENETIC AGE IN PEOPLE AT RISK FOR CRC COULD BE HELPFUL FOR MONITORING THE MOLECULAR RESPONSE TO PREVENTIVE INTERVENTIONS. MOREOVER, IT WOULD BE INTERESTING TO INVESTIGATE WHETHER ABERRANT EPIGENETIC AGING COULD HELP IDENTIFY CRC PATIENTS WITH A HIGH RISK OF RECURRENCE AND A WORST PROGNOSIS, AS WELL AS THOSE WHO RESPOND POORLY TO TREATMENT. YET, THE APPLICATION OF THIS NOVEL CONCEPT IS STILL IN ITS INFANCY, AND FURTHER RESEARCH SHOULD BE ENCOURAGED IN ANTICIPATION OF FUTURE APPLICATIONS IN CLINICAL PRACTICE. 2020