1 6842 95 [MECHANISTIC ISSUES AND PREVENTION STRATEGIES TARGETING OCCUPATIONAL CARCINOGENESIS]. CARCINOGENESIS CAN BE VISUALIZED EITHER AS A MULTISTEP PROCESS (INITIATION, PROMOTION, PROGRESSION, INVASION, AND METASTASIS) OR AS A CONTINUUM OF MUTAGENIC AND MITOGENIC EVENTS, WITH THE CONTRIBUTION OF EPIGENETIC MECHANISMS. THE EXPONENTIAL GROWTH OF THE NEOPLASTIC MASS EXPLAINS THE IMPORTANCE OF SECONDARY PREVENTION (EARLY DIAGNOSIS) AND OF TERTIARY PREVENTION. PRIMARY PREVENTION, WHICH WAS SUCCESSFUL IN CONTROLLING OCCUPATIONAL CANCERS, AIMS AT MINIMIZING EXPOSURES TO CARCINOGENS IN HEALTHY SUBJECTS AND AT FAVORING THE INTAKE OF CHEMOPREVENTIVE AGENTS WITH DIETARY AND PHARMACOLOGICAL AGENTS. BESIDES CHEMICAL CARCINOGENS, OFTEN IN THE FORM OF COMPLEX MIXTURES, THE WORKPLACE MAY INVOLVE EXPOSURES TO PHYSICAL AGENTS, SUCH AS SUNLIGHT AND ARTIFICIAL ILLUMINATION SYSTEMS DELIVERING UV RADIATION, OR TO BIOLOGICAL AGENTS, SUCH AS CHRONIC VIRAL INFECTIONS (HBV, HCV, AND HIV) ASSOCIATED WITH CANCERS. A CONTROVERSIAL ISSUE IS THE OCCURRENCE OF THRESHOLD DOSES FOR CARCINOGENS IN THE WORKPLACE AND THE ENVIRONMENT. 2011 2 3697 19 INFLAMMATORY MARKERS IN CANCER: POTENTIAL RESOURCES. CANCER IS A LEADING CAUSE OF DEATH WORLDWIDE AND A MAJOR BURDEN ON DEVELOPING AND LESS DEVELOPED COUNTRIES OF THE WORLD WITH LIMITED RESOURCES FOR PREVENTION AND EFFECTIVE TREATMENT OF CANCER. ALTHOUGH CANCER IS MULTIFACTORIAL IN ORIGIN, VARIOUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST THAT CHRONIC INFLAMMATION HAS AN IMPORTANT ROLE IN ALL STAGES OF CANCER, FROM INITIATION TO PROGRESSION AND EVEN SURVIVAL OF THE PATIENT. INFLAMMATORY PRODUCTS LIKE CYTOKINES, CHEMOKINES, LEUCOCYTES, PROSTAGLANDINS, CYCLOOXYGENASE, REACTIVE OXYGEN AND NITROGEN SPECIES, METALLOPROTEINASE INDUCE GENETIC AND EPIGENETIC CHANGES IN NORMAL CELLS DAMAGING ITS DNA, INHIBITING ITS REPAIR, ALTERING TRANSCRIPTION FACTORS, PREVENTING APOPTOSIS, AND STIMULATING ANGIOGENESIS, AND THUS RESULTING IN CARCINOGENESIS. THUS, THESE INFLAMMATORY MEDIATORS HAVE A POTENTIAL ROLE TO BECOME CANCER BIOMARKERS FOR ALL STAGES OF CANCER AS MANY OF THEM CAN BE MEASURED IN A COST-EFFECTIVE MANNER. HOWEVER, LARGE SCALE PROSPECTIVE TRIALS ARE REQUIRED TO VALIDATE THESE POTENTIAL CANCER BIOMARKERS. NONETHELESS, A TRANSITION FROM POTENTIAL TO PRACTICAL UTILIZATION OF THESE MARKERS WILL BE AN EFFECTIVE TOOL FOR THE AMELIORATION OF CANCER BURDEN AND MORTALITY IN A RESOURCE LIMITED SETTING. 2020 3 1010 24 CHRONICALLY ELEVATED PROLIFERATION AS A RISK FACTOR FOR NEOPLASIA. CHRONIC DISEASE CONDITIONS THAT ARE ASSOCIATED WITH ELEVATED PROLIFERATION ARE WELL ESTABLISHED AS RISK FACTORS FOR CANCER DEVELOPMENT. THESE MAY BE DUE TO VIRUSES (FOR EXAMPLE, IN THE CASE OF HEPATITIS AND LIVER CANCER), BACTERIAL INFECTIONS, PARASITE INFESTATION OR PHYSICAL TRAUMA. IN ADDITION TO THESE EXOGENOUS AGENTS THERE ARE ALSO METABOLIC ABNORMALITIES THAT CAN CONTRIBUTE, CAUSED BY GENETIC OR EPIGENETIC INFLUENCE. IN THE LATTER CASE, AN INCREASE IN SERUM LEVELS OF THE HORMONES OESTROGEN, TESTOSTERONE AND INSULIN MAY BE OF SPECIAL IMPORTANCE. THE PRESENT REVIEW CONCENTRATES ATTENTION ON FACTORS THAT INDUCE ELEVATED CELL TURNOVER AND FOR WHICH THERE IS EPIDEMIOLOGICAL AND/OR EXPERIMENTAL EVIDENCE OF A LINK WITH NEOPLASIA, WITH PARTICULAR STRESS ON THE INDIVIDUAL ORGAN OR TISSUE LEVEL. 1998 4 5493 20 REVIEW OF IN VITRO TEST SYSTEMS USING DNA DAMAGE AND REPAIR FOR SCREENING OF CHEMICAL CARCINOGENS. CHEMICAL CARCINOGENS ARE MECHANISTICALLY CLASSIFIED AS GENOTOXIC WHICH INTERACT DIRECTLY WITH DNA, AND EPIGENETIC WHICH CAUSE CHRONIC TISSUE INJURY, HORMONAL IMBALANCE, AND PROMOTIONAL EFFECTS. THIS REVIEW EVALUATES IN VITRO TESTS FOR THEIR CONTRIBUTION TO A BATTERY FOR IDENTIFYING GENOTOXIC CHEMICAL CARCINOGENS. IN ADDITION TO BACTERIAL MUTAGENIC ASSAYS, NONSPECIFIC DNA DAMAGE/REPAIR TESTS ARE RECOMMENDED FOR SCREENING CHEMICALS, IN PARTICULAR THE HEPATOCYTE PRIMARY CULTURE/DNA REPAIR TEST. 1979 5 731 25 CANCER CHEMOPREVENTION: CLASSIC AND EPIGENETIC MECHANISMS INHIBITING TUMORIGENESIS. WHAT HAVE WE LEARNED SO FAR? CANCERS DERIVE FROM STEP BY STEP PROCESSES WHICH ARE DIFFERENTIATED BY THE PROGRESSIVELY ACCUMULATED MUTATIONS. FOR SOME TUMORS THERE IS A CLEAR PROGRESSIVE ADVANCEMENT FROM BENIGN LESIONS TO MALIGNANCY AND FOR THESE, PREVENTIVE SCREENING PROGRAMS EXIST. IN SUCH CASES HAVING THOSE BENIGN LESIONS ARE A CLEAR INDICATOR OF PREDISPOSITION WHILE FOR SOME OTHER CASES, FAMILIAL PATTERNS OF CANCER INCIDENCE AND THE IDENTIFICATION OF MUTATIONS ARE THE MAIN INDICATORS OF HIGHER RISK FOR HAVING THE DISEASE. FOR PATIENTS IDENTIFIED AS HAVING PREDISPOSITION, CHEMOPREVENTION IS A GOAL AND IN SOME CASES A POSSIBILITY. CHEMOPREVENTION IS THE USE OF ANY COMPOUND, EITHER NATURAL OR SYNTHETIC THAT ABROGATES CARCINOGENESIS OR TUMOR PROGRESSION, THROUGH DIFFERENT MECHANISMS, SOME OF WHICH HAVE ALREADY BEEN DESCRIBED. FOR EXAMPLE, THE CLASSIC MECHANISMS MAY INVOLVE ACTIVATION OF FREE RADICAL SCAVENGING ENZYMES, CONTROL OF CHRONIC INFLAMMATION, AND DOWNREGULATION OF SPECIFIC SIGNALING PATHWAYS. MORE RECENTLY, EPIGENETICS ALLOWED FURTHER UNDERSTANDING OF THE CHEMOPREVENTIVE POTENTIAL OF SEVERAL AGENTS, SUCH AS SULFORAPHANE, GREEN TEA DERIVED COMPOUNDS, RESVERATROL, ISOFLAVONES, AND OTHERS WHICH WE EXPLOIT IN THIS REVIEW ARTICLE. THROUGHOUT THE TEXT WE DISCUSS THE PROPERTIES COMPOUNDS SHOULD HAVE IN ORDER TO BE CLASSIFIED AS CHEMOPREVENTIVE ONES AND THE CHALLENGES IN TRANSLATIONAL RESEARCH IN THIS AREA, AS LOTS OF THE SUCCESS ACHIEVED IN VITRO CANNOT BE TRANSLATED INTO THE CLINICAL SETTINGS, DUE TO SEVERAL DIFFERENT DRAWBACKS, WHICH INCLUDE TOXICITY, COST, DOSE DEFINITION, PATIENT ADHERENCE, AND REGIMEN OF USE. 2018 6 1844 28 EFFECTS OF THE LIFESTYLE HABITS IN BREAST CANCER TRANSCRIPTIONAL REGULATION. THROUGH RESEARCH CARRIED OUT IN THE LAST 25 YEARS ABOUT THE BREAST CANCER ETIOLOGY, IT HAS BEEN POSSIBLE TO ESTIMATE THAT LESS THAN 10 % OF PATIENTS WHO ARE DIAGNOSED WITH THE CONDITION ARE CARRIERS OF SOME GERMLINE OR SOMATIC MUTATION. THE CLINICAL REPORTS OF BREAST CANCER PATIENTS WITH HEALTHY TWINS AND THE DEVELOPMENT OF DISEASE IN WOMEN WITHOUT HIGH PENETRANCE MUTATIONS DETECTED, WARN THE PARTICIPATION MORE FACTORS IN THE TRANSFORMATION PROCESS. THE HIGH INCIDENCE OF MAMMARY ADENOCARCINOMA IN THE MODERN WOMAN AND THE URGENT NEED FOR NEW METHODS OF PREVENTION AND EARLY DETECTION HAVE DEMANDED MORE INFORMATION ABOUT THE ROLE THAT ENVIRONMENT AND LIFESTYLE HAVE ON THE TRANSFORMATION OF MAMMARY GLAND EPITHELIAL CELLS. OBESITY, ALCOHOLISM AND SMOKING ARE FACTORS THAT HAVE SHOWN A CLOSE CORRELATION WITH THE RISK OF DEVELOPING BREAST CANCER. AND ALTHOUGH THESE CONDITIONS AFFECT DIFFERENT CELL REGULATION LEVELS, THE STUDY OF ITS EFFECTS IN THE MECHANISMS OF TRANSCRIPTIONAL AND EPIGENETIC REGULATION IS CONSIDERED CRITICAL FOR A BETTER UNDERSTANDING OF THE LOSS OF IDENTITY OF EPITHELIAL CELLS DURING CARCINOGENESIS OF THIS TISSUE. THE MAIN OBJECTIVE OF THIS REVIEW WAS TO ESTABLISH THE IMPORTANCE OF CHANGES OCCURRING TO TRANSCRIPTIONAL LEVEL IN THE MAMMARY GLAND AS A CONSEQUENCE OF ACUTE OR CHRONIC EXPOSURE TO HARMFUL PRODUCTS SUCH AS OBESITY-CAUSING FOODS, ETHANOL AND CIGARETTE SMOKE COMPONENTS. AT ANALYZE THE MAIN STUDIES RELATED TO TOPIC, IT HAS CONCLUDED THAT THE UNDERSTANDING OF EFFECTS CAUSED BY THE LIFESTYLE FACTORS IN PERFORMANCE OF THE TRANSCRIPTIONAL MECHANISMS THAT DETERMINE GENE EXPRESSION OF THE MAMMARY GLAND EPITHELIAL CELLS, MAY HELP EXPLAIN THE DEVELOPMENT OF THIS DISEASE IN WOMEN WITHOUT GENETIC PROPENSITY AND DIFFERENT PHENOTYPIC MANIFESTATIONS OF THIS CANCER TYPE. 2016 7 1970 21 EPIGENETIC ALTERATIONS AND OCCUPATIONAL EXPOSURE TO BENZENE, FIBERS, AND HEAVY METALS ASSOCIATED WITH TUMOR DEVELOPMENT (REVIEW). THE CHRONIC OCCUPATIONAL EXPOSURE TO CONTAMINANTS AND CARCINOGENS LEADS TO THE DEVELOPMENT OF CANCER. OVER THE PAST DECADES, MANY CARCINOGENS HAVE BEEN FOUND IN THE OCCUPATIONAL ENVIRONMENT AND THEIR PRESENCE IS OFTEN ASSOCIATED WITH AN INCREASED INCIDENCE OF CANCER. ACCORDING TO THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC), THE MAJORITY OF CARCINOGENS ARE CLASSIFIED AS 'PROBABLE' AND 'POSSIBLE' HUMAN CARCINOGENS, WHILE, DIRECT EVIDENCE OF CARCINOGENICITY IS PROVIDED IN EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES. ADDITIONALLY, ACCUMULATING EVIDENCE SUGGESTS THAT EPIGENETIC ALTERATIONS MAY BE EARLY INDICATORS OF GENOTOXIC AND NON-GENOTOXIC CARCINOGEN EXPOSURE. IN THE PRESENT REVIEW, THE RELATIONSHIP BETWEEN EXPOSURES TO BENZENE, MINERAL FIBERS, METALS AND EPIGENETIC ALTERATIONS ARE DISCUSSED AS THE MOST IMPORTANT CANCER RISK FACTORS DURING WORK ACTIVITIES. 2017 8 1958 18 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 9 3683 26 INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. CONTEXT: CHRONIC INFLAMMATION OF THE PROSTATE HAS BEEN ASSOCIATED WITH PRENEOPLASTIC LESIONS AND CANCER DEVELOPMENT. MULTIPLE CAUSES HAVE BEEN CONSIDERED FOR CHRONIC INFLAMMATION OF THE PROSTATE. INFLAMMATORY CYTOKINES SUCH AS INTERLEUKINS ARE IMPLICATED IN PROSTATE CARCINOGENESIS AND DEVELOPMENT. OBJECTIVE: TO EVALUATE LITERATURE PUBLISHED ON ETIOLOGICAL FACTORS, URINARY MICROBIOTA, MORPHOLOGICAL FEATURES OF PROLIFERATIVE INFLAMMATORY ATROPHY AND HIGH-GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA, GENETIC POLYMORPHISMS, INFLAMMATORY STRESS, AND CYTOKINE SIGNALING. EVIDENCE ACQUISITION: WE SEARCHED LITERATURE FROM PUBMED FROM 2010 AND ALSO INCLUDED THE MOST IMPORTANT PUBLICATIONS FROM THE PREVIOUS PERIOD. EVIDENCE SYNTHESIS: PROSTATE CANCER INFLAMMATION AND PREMALIGNANT LESIONS HAVE BEEN FREQUENTLY DISCUSSED IN SCIENTIFIC LITERATURE. A LIMITED NUMBER OF MODELS ARE AVAILABLE FOR STUDYING INFLAMMATION AND PREMALIGNANT LESIONS. HOWEVER, MORPHOLOGICAL PATHOLOGY COULD BE COMPLEMENTED BY ANALYSIS OF GENE POLYMORPHISMS IN THESE PATIENTS AND APPROPRIATE FUNCTIONAL STUDIES. CONCLUSIONS: PROSTATITIS COULD BE CAUSED BY BACTERIAL OR VIRAL INFECTIONS, DIETARY COMPOUNDS, AND CHANGES IN TESTOSTERONE:ESTRADIOL RATIO. IN SOME CASES, THE MICROBIOTA CAN EXERT DIRECT EFFECTS ON CANCER DEVELOPMENT. PROSTATE INFLAMMATORY ATROPHY OR HIGH GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA HAVE BEEN ASSOCIATED WITH RESPONSE TO CELLULAR STRESS AND HAVE BEEN DISCUSSED IN CONNECTION TO EARLY CANCER DEVELOPMENT. A LARGE NUMBER OF GENETIC POLYMORPHISMS HAVE BEEN IDENTIFIED IN INFLAMMATORY PROSTATE. GENETIC AND EPIGENETIC ALTERATIONS MAY BE A CONSEQUENCE OF THE PROINFLAMMATORY STRESS IN THE PROSTATE. PROINFLAMMATORY CYTOKINES INTERLEUKIN-6 AND -8 CONTRIBUTE TO PROSTATE MALIGNANCY; HOWEVER, THEIR FUNCTION WAS MORE FREQUENTLY INVESTIGATED IN CANCER TISSUE RATHER THAN IN INFLAMMATION. PATIENT SUMMARY: WE PERFORMED A REVIEW OF RECENT LITERATURE RELATED TO PROSTATE INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. NEW FUNCTIONAL APPROACHES ARE REQUIRED FOR A BETTER UNDERSTANDING OF THE ROLE OF INFLAMMATION AND CANCER DEVELOPMENT. 2016 10 551 27 AUTOIMMUNITY AS AN ETIOLOGICAL FACTOR OF CANCER: THE TRANSFORMATIVE POTENTIAL OF CHRONIC TYPE 2 INFLAMMATION. RECENT EPIDEMIOLOGICAL STUDIES HAVE FOUND AN ALARMING TREND OF INCREASED CANCER INCIDENCE IN ADULTS YOUNGER THAN 50 YEARS OF AGE AND PROJECTED A SUBSTANTIAL RISE IN CANCER INCIDENCE OVER THE NEXT 10 YEARS IN THIS AGE GROUP. THIS TREND WAS EXEMPLIFIED IN THE INCIDENCE OF NON-CARDIA GASTRIC CANCER AND ITS DISPROPORTIONATE IMPACT ON NON-HISPANIC WHITE FEMALES UNDER THE AGE OF 50. THE TREND IS CONCURRENT WITH THE INCREASING INCIDENCE OF AUTOIMMUNE DISEASES IN INDUSTRIALIZED COUNTRIES, SUGGESTING A CAUSAL LINK BETWEEN THE TWO. WHILE AUTOIMMUNITY HAS BEEN SUSPECTED TO BE A RISK FACTOR FOR SOME CANCERS, THE EXACT MECHANISMS UNDERLYING THE CONNECTION BETWEEN AUTOIMMUNITY AND CANCER REMAIN UNCLEAR AND ARE OFTEN CONTROVERSIAL. THE LINK HAS BEEN ATTRIBUTED TO SEVERAL MEDIATORS SUCH AS IMMUNE SUPPRESSION, INFECTION, DIET, ENVIRONMENT, OR, PERHAPS MOST PLAUSIBLY, CHRONIC INFLAMMATION BECAUSE OF ITS WELL-RECOGNIZED ROLE IN TUMORIGENESIS. IN THAT REGARD, AUTOIMMUNE CONDITIONS ARE COMMON CAUSES OF CHRONIC INFLAMMATION AND MAY TRIGGER REPETITIVE CYCLES OF ANTIGEN-SPECIFIC CELL DAMAGE, TISSUE REGENERATION, AND WOUND HEALING. ILLUSTRATING THE CONNECTION BETWEEN AUTOIMMUNE DISEASES AND CANCER ARE PATIENTS WHO HAVE AN INCREASED RISK OF CANCER DEVELOPMENT ASSOCIATED WITH GENETICALLY PREDISPOSED INSUFFICIENCY OF CYTOTOXIC T LYMPHOCYTE-ASSOCIATED PROTEIN 4 (CTLA4), A PROTOTYPICAL IMMUNE CHECKPOINT AGAINST AUTOIMMUNITY AND ONE OF THE MAIN TARGETS OF CANCER IMMUNE THERAPY. THE TUMORIGENIC PROCESS TRIGGERED BY CTLA4 INSUFFICIENCY HAS BEEN SHOWN IN A MOUSE MODEL TO BE DEPENDENT ON THE TYPE 2 CYTOKINES INTERLEUKIN-4 (IL4) AND INTERLEUKIN-13 (IL13). IN THIS TYPE 2 INFLAMMATORY MILIEU, CROSSTALK WITH TYPE 2 IMMUNE CELLS MAY INITIATE EPIGENETIC REPROGRAMMING OF EPITHELIAL CELLS, LEADING TO A METAPLASTIC DIFFERENTIATION AND EVENTUALLY MALIGNANT TRANSFORMATION EVEN IN THE ABSENCE OF CLASSICAL ONCOGENIC MUTATIONS. THOSE FINDINGS COMPLEMENT A LARGE BODY OF EVIDENCE FOR TYPE 1, TYPE 3, OR OTHER INFLAMMATORY MEDIATORS IN INFLAMMATORY TUMORIGENESIS. THIS REVIEW ADDRESSES THE POTENTIAL OF AUTOIMMUNITY AS A CAUSAL FACTOR FOR TUMORIGENESIS, THE UNDERLYING INFLAMMATORY MECHANISMS THAT MAY VARY DEPENDING ON HOST-ENVIRONMENT VARIATIONS, AND IMPLICATIONS TO CANCER PREVENTION AND IMMUNOTHERAPY. 2021 11 186 18 ACCUMULATION OF GENETIC AND EPIGENETIC ALTERATIONS IN NORMAL CELLS AND CANCER RISK. CANCERS DEVELOP DUE TO THE ACCUMULATION OF GENETIC AND EPIGENETIC ALTERATIONS. GENETIC ALTERATIONS ARE INDUCED BY AGING, MUTAGENIC CHEMICALS, ULTRAVIOLET LIGHT, AND OTHER FACTORS; WHEREAS, EPIGENETIC ALTERATIONS ARE MAINLY BY AGING AND CHRONIC INFLAMMATION. THE ACCUMULATION AND PATTERNS OF ALTERATIONS IN NORMAL CELLS REFLECT OUR PAST EXPOSURE LEVELS AND LIFE HISTORY. MOST ACCUMULATED ALTERATIONS ARE CONSIDERED AS PASSENGERS, BUT THEIR ACCUMULATION IS CORRELATED WITH CANCER DRIVERS. THIS HAS BEEN SHOWN FOR ABERRANT DNA METHYLATION BUT HAS ONLY BEEN SPECULATED FOR GENETIC ALTERATIONS. HOWEVER, RECENT TECHNOLOGICAL ADVANCEMENTS HAVE ENABLED MEASUREMENT OF RARE POINT MUTATIONS, AND STUDIES HAVE SHOWN THAT THEIR ACCUMULATION LEVELS ARE INDEED CORRELATED WITH CANCER RISK. WHEN THE ACCUMULATION LEVELS OF ABERRANT DNA METHYLATION AND POINT MUTATIONS ARE COMBINED, RISK PREDICTION BECOMES EVEN MORE ACCURATE. WHEN HIGH LEVELS OF ALTERATIONS ACCUMULATE, THE TISSUE HAS A HIGH RISK OF DEVELOPING CANCER OR EVEN MULTIPLE CANCERS AND IS CONSIDERED AS A "CANCERIZATION FIELD", WITH OR WITHOUT EXPANSION OF PHYSIOLOGICAL PATCHES OF CLONAL CELLS. IN THIS REVIEW, WE DESCRIBE THE FORMATION OF A CANCERIZATION FIELD AND HOW WE CAN APPLY ITS DETECTION IN PRECISION CANCER RISK DIAGNOSIS. 2019 12 5373 24 RECENT ADVANCES IN UNDERSTANDING THE ROLE OF DIET AND OBESITY IN THE DEVELOPMENT OF COLORECTAL CANCER. COLORECTAL CANCER (CRC) IS A MAJOR CAUSE OF PREMATURE DEATH IN THE UK AND MANY DEVELOPED COUNTRIES. HOWEVER, THE RISK OF DEVELOPING CRC IS WELL RECOGNISED TO BE ASSOCIATED NOT ONLY WITH DIET BUT ALSO WITH OBESITY AND LACK OF EXERCISE. WHILE EPIDEMIOLOGICAL EVIDENCE SHOWS AN ASSOCIATION WITH FACTORS SUCH AS HIGH RED MEAT INTAKE AND LOW INTAKE OF VEGETABLES, FIBRE AND FISH, THE MECHANISMS UNDERLYING THESE EFFECTS ARE ONLY NOW BEING ELUCIDATED. CRC DEVELOPS OVER MANY YEARS AND IS TYPICALLY CHARACTERISED BY AN ACCUMULATION OF MUTATIONS, WHICH MAY ARISE AS A CONSEQUENCE OF INHERITED POLYMORPHISMS IN KEY GENES, BUT MORE COMMONLY AS A RESULT OF SPONTANEOUSLY ARISING MUTATIONS AFFECTING GENES CONTROLLING CELL PROLIFERATION, DIFFERENTIATION, APOPTOSIS AND DNA REPAIR. EPIGENETIC CHANGES ARE OBSERVED THROUGHOUT THE PROGRESS FROM NORMAL MORPHOLOGY THROUGH FORMATION OF ADENOMA, AND THE SUBSEQUENT DEVELOPMENT OF CARCINOMA. THE REASONS WHY THIS ACCUMULATION OF LOSS OF HOMOEOSTATIC CONTROLS ARISES ARE UNCLEAR BUT CHRONIC INFLAMMATION HAS BEEN PROPOSED TO PLAY A CENTRAL ROLE. OBESITY IS ASSOCIATED WITH INCREASED PLASMA LEVELS OF CHEMOKINES AND ADIPOKINES CHARACTERISTIC OF CHRONIC SYSTEMIC INFLAMMATION, AND DIETARY FACTORS SUCH AS FISH OILS AND PHYTOCHEMICALS HAVE BEEN SHOWN TO HAVE ANTI-INFLAMMATORY PROPERTIES AS WELL AS MODULATING ESTABLISHED RISK FACTORS SUCH AS APOPTOSIS AND CELL PROLIFERATION. THERE IS ALSO SOME EVIDENCE THAT DIET CAN MODIFY EPIGENETIC CHANGES. THIS PAPER BRIEFLY REVIEWS THE CURRENT STATE OF KNOWLEDGE IN RELATION TO CRC DEVELOPMENT AND CONSIDERS EVIDENCE FOR POTENTIAL MECHANISMS BY WHICH DIET MAY MODIFY RISK. 2011 13 266 30 ADVERSE OUTCOME PATHWAYS FOR IONIZING RADIATION AND BREAST CANCER INVOLVE DIRECT AND INDIRECT DNA DAMAGE, OXIDATIVE STRESS, INFLAMMATION, GENOMIC INSTABILITY, AND INTERACTION WITH HORMONAL REGULATION OF THE BREAST. KNOWLEDGE ABOUT ESTABLISHED BREAST CARCINOGENS CAN SUPPORT IMPROVED AND MODERNIZED TOXICOLOGICAL TESTING METHODS BY IDENTIFYING KEY MECHANISTIC EVENTS. IONIZING RADIATION (IR) INCREASES THE RISK OF BREAST CANCER, ESPECIALLY FOR WOMEN AND FOR EXPOSURE AT YOUNGER AGES, AND EVIDENCE OVERALL SUPPORTS A LINEAR DOSE-RESPONSE RELATIONSHIP. WE USED THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK TO OUTLINE AND EVALUATE THE EVIDENCE LINKING IONIZING RADIATION WITH BREAST CANCER FROM MOLECULAR INITIATING EVENTS TO THE ADVERSE OUTCOME THROUGH INTERMEDIATE KEY EVENTS, CREATING A QUALITATIVE AOP. WE IDENTIFIED KEY EVENTS BASED ON REVIEW ARTICLES, SEARCHED PUBMED FOR RECENT LITERATURE ON KEY EVENTS AND IR, AND IDENTIFIED ADDITIONAL PAPERS USING REFERENCES. WE MANUALLY CURATED PUBLICATIONS AND EVALUATED DATA QUALITY. IONIZING RADIATION DIRECTLY AND INDIRECTLY CAUSES DNA DAMAGE AND INCREASES PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES (RONS). RONS LEAD TO DNA DAMAGE AND EPIGENETIC CHANGES LEADING TO MUTATIONS AND GENOMIC INSTABILITY (GI). PROLIFERATION AMPLIFIES THE EFFECTS OF DNA DAMAGE AND MUTATIONS LEADING TO THE AO OF BREAST CANCER. SEPARATELY, RONS AND DNA DAMAGE ALSO INCREASE INFLAMMATION. INFLAMMATION CONTRIBUTES TO DIRECT AND INDIRECT EFFECTS (EFFECTS IN CELLS NOT DIRECTLY REACHED BY IR) VIA POSITIVE FEEDBACK TO RONS AND DNA DAMAGE, AND SEPARATELY INCREASES PROLIFERATION AND BREAST CANCER THROUGH PRO-CARCINOGENIC EFFECTS ON CELLS AND TISSUE. FOR EXAMPLE, GENE EXPRESSION CHANGES ALTER INFLAMMATORY MEDIATORS, RESULTING IN IMPROVED SURVIVAL AND GROWTH OF CANCER CELLS AND A MORE HOSPITABLE TISSUE ENVIRONMENT. ALL OF THESE EVENTS OVERLAP AT MULTIPLE POINTS WITH EVENTS CHARACTERISTIC OF "BACKGROUND" INDUCTION OF BREAST CARCINOGENESIS, INCLUDING HORMONE-RESPONSIVE PROLIFERATION, OXIDATIVE ACTIVITY, AND DNA DAMAGE. THESE OVERLAPS MAKE THE BREAST PARTICULARLY SUSCEPTIBLE TO IONIZING RADIATION AND REINFORCE THAT THESE BIOLOGICAL ACTIVITIES ARE IMPORTANT CHARACTERISTICS OF CARCINOGENS. AGENTS THAT INCREASE THESE BIOLOGICAL PROCESSES SHOULD BE CONSIDERED POTENTIAL BREAST CARCINOGENS, AND PREDICTIVE METHODS ARE NEEDED TO IDENTIFY CHEMICALS THAT INCREASE THESE PROCESSES. TECHNIQUES ARE AVAILABLE TO MEASURE RONS, DNA DAMAGE AND MUTATION, CELL PROLIFERATION, AND SOME INFLAMMATORY PROTEINS OR PROCESSES. IMPROVED ASSAYS ARE NEEDED TO MEASURE GI AND CHRONIC INFLAMMATION, AS WELL AS THE INTERACTION WITH HORMONALLY DRIVEN DEVELOPMENT AND PROLIFERATION. SEVERAL METHODS MEASURE DIVERSE EPIGENETIC CHANGES, BUT IT IS NOT CLEAR WHICH CHANGES ARE RELEVANT TO BREAST CANCER. IN ADDITION, MOST TOXICOLOGICAL ASSAYS ARE NOT CONDUCTED IN MAMMARY TISSUE, AND SO IT IS A PRIORITY TO EVALUATE IF RESULTS FROM OTHER TISSUES ARE GENERALIZABLE TO BREAST, OR TO CONDUCT ASSAYS IN BREAST TISSUE. DEVELOPING AND APPLYING THESE ASSAYS TO IDENTIFY EXPOSURES OF CONCERN WILL FACILITATE EFFORTS TO REDUCE SUBSEQUENT BREAST CANCER RISK. 2020 14 1918 29 ENVIRONMENTAL CARCINOGENESIS AND TRANSGENERATIONAL TRANSMISSION OF CARCINOGENIC RISK: FROM GENETICS TO EPIGENETICS. THE DOMINANT PATHOGENIC MODEL, SOMATIC MUTATION THEORY (SMT), CONSIDERS CARCINOGENESIS AS A 'GENETIC ACCIDENT' DUE TO THE ACCUMULATION OF 'STOCHASTIC' DNA MUTATIONS. THIS MODEL WAS PROPOSED AND ACCEPTED BY THE SCIENTIFIC COMMUNITY WHEN CANCER MAINLY AFFECTED THE ELDERLY, BUT IT DOES NOT EXPLAIN THE EPIDEMIOLOGICAL OBSERVATION OF THE CONTINUOUS INCREASE IN CANCER INCIDENCE AMONG CHILDREN AND YOUNG ADULTS. SOMATIC MUTATION THEORY HAS BEEN PROPOSED FOR A REVISION BASED ON THE EMERGING EXPERIMENTAL EVIDENCE, AS IT DOES NOT FULLY ADDRESS SOME ISSUES THAT HAVE PROVEN TO BE CRUCIAL FOR CARCINOGENESIS, NAMELY: THE INFLAMMATORY CONTEXT OF CANCER; THE KEY ROLE PLAYED BY THE STROMA, MICROENVIRONMENT, ENDOTHELIAL CELLS, ACTIVATED MACROPHAGES, AND SURROUNDING TISSUES; AND THE DISTORTED DEVELOPMENTAL COURSE FOLLOWED BY THE NEOPLASTIC TISSUE. FURTHERMORE, SMT IS OFTEN NOT ABLE TO CONSIDER EITHER THE EXISTENCE OF SPECIFIC MUTATIONS RESULTING IN A WELL-DEFINED CANCER TYPE, OR A CLEAR RELATIONSHIP BETWEEN MUTATIONS AND TUMOR PROGRESSION. MOREOVER, IT DOES NOT EXPLAIN THE MECHANISM OF ACTION OF THE NON-MUTAGENIC AND ENVIRONMENTAL CARCINOGENS. IN THE LAST DECADE, CANCER RESEARCH HAS HIGHLIGHTED THE PROMINENT ROLE OF AN ALTERED REGULATION OF GENE EXPRESSION, SUGGESTING THAT CANCER SHOULD BE CONSIDERED AS A RESULT OF A POLYCLONAL EPIGENETIC DISRUPTION OF STEM/PROGENITOR CELLS, MEDIATED BY TUMOUR-INDUCING GENES. THE MATERNAL AND FETAL EXPOSURE TO A WIDE RANGE OF CHEMICALS AND ENVIRONMENTAL CONTAMINANTS IS RAISING THE ATTENTION OF THE SCIENTIFIC COMMUNITY. INDEED, THE MOST POWERFUL PROCARCINOGENIC MECHANISMS OF ENDOCRINE DISRUPTORS AND OTHER POLLUTANTS IS LINKED TO THEIR POTENTIAL TO INTERFERE EPIGENETICALLY WITH THE EMBRYO-FETAL PROGRAMMING OF TISSUES AND ORGANS, ALTERING THE REGULATION OF THE GENES INVOLVED IN THE CELL CYCLE, CELL PROLIFERATION, APOPTOSIS, AND OTHER KEY SIGNALING PATHWAYS. THE EMBRYO-FETAL EXPOSURE TO ENVIRONMENTAL, STRESSFUL, AND PROINFLAMMATORY TRIGGERS (FIRST HIT), SEEMS TO ACT AS A 'DISEASE PRIMER', MAKING FETAL CELLS AND TISSUES MORE SUSCEPTIBLE TO THE SUBSEQUENT ENVIRONMENTAL EXPOSURES (SECOND HIT), TRIGGERING THE CARCINOGENIC PATHWAYS. FURTHERMORE, EVEN AT THE MOLECULAR LEVEL, IN CARCINOGENESIS, 'EPIGENETICS PRECEDES GENETICS' AS GLOBAL DNA HYPOMETHYLATION, AND THE HYPERMETHYLATION OF TUMOR SUPPRESSOR GENES ARE COMMON BOTH IN CANCEROUS AND IN PRECANCEROUS CELLS, AND GENERALLY PRECEDE MUTATIONS. THESE EPIGENETIC MODELS MAY BETTER EXPLAIN THE INCREASE OF CANCER AND CHRONIC/DEGENERATIVE DISEASES IN THE LAST DECADES AND COULD BE USEFUL TO ADOPT APPROPRIATE PRIMARY PREVENTION MEASURES, ESSENTIALLY BASED ON THE REDUCTION OF MATERNAL-FETAL AND CHILD EXPOSURE TO SEVERAL PROCARCINOGENIC AGENTS AND FACTORS DISPERSED IN THE ENVIRONMENT AND IN THE FOOD-CHAINS, AS RECENTLY SUGGESTED BY THE WORLD HEALTH ORGANIZATION. 2018 15 5282 19 PROMOTION OF HEPATOCARCINOGENESIS IN HUMANS AND ANIMAL MODELS. RISK ASSESSMENT BASED ON RODENT CARCINOGENICITY DATA DEPENDS ON THE ASSUMPTION OF SIMILARITY BETWEEN RODENTS AND HUMANS. WHILE THIS ASSUMPTION IS CONCEIVABLE IN THE CASE OF GENOTOXIC INITIATING CARCINOGENS, CONSIDERABLE SPECIES DIFFERENCES HAVE BEEN OBSERVED WITH NONGENOTOXIC TUMOR PROMOTERS. THIS HETEROGENEOUS GROUP OF AGENTS INCREASES THE PROBABILITY OF CANCER BY STIMULATING SELECTION AND CLONAL EXPANSION OF CELLS TRANSFORMED DURING TUMOR INITIATION. SINCE TUMOR PROMOTERS DIFFERENTIALLY AFFECT NORMAL TISSUE AND PRENEOPLASTIC CELL CLONES, THEIR ACTION CANNOT BE DISCUSSED WITHOUT KNOWLEDGE OF PERSISTENT GENOMIC AND EPIGENETIC ALTERATIONS OCCURRING DURING INITIATION AND FORMATION OF PRENEOPLASTIC CELLS. CHEMICAL CARCINOGENESIS, AND IN PARTICULAR, TUMOR PROMOTION, IS KNOWN TO BE TISSUE SPECIFIC. WE FOCUS ON HEPATOCARCINOGENESIS IN HUMANS AND IN ANIMAL MODELS AND EMPHASIZE TWO DIFFERENT MODES OF ACTION: (1) CHRONIC CYTOTOXICITY LEADING TO PROMOTION OF LIVER CARCINOGENESIS IN BOTH HUMANS AND ANIMAL MODELS; (2) SUSTAINED ACTIVATION OF ORPHAN RECEPTORS SUCH AS CAR, PPARALPHA AND AH RECEPTOR LEADING TO PROMOTION OF RODENT BUT PROBABLY NOT HUMAN HEPATOCARCINOGENESIS. FURTHER STUDIES ON THE DIFFERENT MODES OF ACTION MAY HELP TO AVOID OVERESTIMATION OF THE RISK OF LIVER TUMOR PROMOTION. 2008 16 4429 23 MOLECULAR BIOLOGY AS A TOOL FOR THE TREATMENT OF CANCER. CANCER IS A GENETIC DISEASE CHARACTERIZED BY UNCONTROLLED CELL GROWTH AND METASTASIS. CANCER CAN HAVE A NUMBER OF CAUSES, SUCH THE ACTIVATION OF ONCOGENES, THE INACTIVATION OF TUMOR-SUPPRESSING GENES, MUTAGENESIS PROVOKED BY EXTERNAL FACTORS, AND EPIGENETIC MODIFICATIONS. THE DEVELOPMENT OF DIAGNOSTIC TOOLS AND TREATMENTS USING A MOLECULAR BIOLOGICAL APPROACH PERMITS THE USE OF SENSITIVE, LOW-COST, NONINVASIVE TESTS FOR CANCER PATIENTS. BIOMARKERS CAN BE USED TO PROVIDE RAPID, PERSONALIZED ONCOLOGY, IN PARTICULAR THE MOLECULAR DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA, AND GASTRIC, COLON, AND BREAST CANCERS. MOLECULAR TESTS BASED ON DNA METHYLATION CAN ALSO BE USED TO DIRECT TREATMENTS OR EVALUATE THE TOXIC EFFECTS OF CHEMOTHERAPY. THE ADEQUATE DIAGNOSIS, PROGNOSIS, AND PREDICTION OF THE RESPONSE OF CANCER PATIENTS TO TREATMENT ARE ESSENTIAL TO ENSURE THE MOST EFFECTIVE THERAPY, REDUCE THE DAMAGING EFFECTS OF TREATMENT, AND DIRECT THE THERAPY TO SPECIFIC TARGETS, AND IN THIS CONTEXT, MOLECULAR BIOLOGY HAS BECOME INCREASINGLY IMPORTANT IN ONCOLOGY. IN THIS BRIEF REVIEW, WE WILL DEMONSTRATE THE FUNDAMENTAL IMPORTANCE OF MOLECULAR BIOLOGY FOR THE TREATMENT OF THREE TYPES OF CANCER-CHRONIC MYELOID LEUKEMIA, HEREDITARY DIFFUSE GASTRIC CANCER, AND ASTROCYTOMAS (SPORADIC TUMORS OF THE CENTRAL NERVOUS SYSTEM). IN EACH OF THESE THREE MODELS, DISTINCT BIOLOGICAL MECHANISMS ARE INVOLVED IN THE TRANSFORMATION OF THE CELLS, BUT IN ALL CASES, MOLECULAR BIOLOGY IS FUNDAMENTAL TO THE DEVELOPMENT OF PERSONALIZED ANALYSES FOR EACH PATIENT AND EACH TYPE OF NEOPLASIA, AND TO GUARANTEE THE SUCCESS OF THE TREATMENT. 2018 17 5742 16 SMOKING MOLECULAR DAMAGE IN BRONCHIAL EPITHELIUM. OUR UNDERSTANDING OF THE MOLECULAR PATHOLOGY OF LUNG CANCER IS ADVANCING RAPIDLY WITH SEVERAL SPECIFIC GENES AND CHROMOSOMAL REGIONS BEING IDENTIFIED. LUNG CANCER APPEARS TO REQUIRE MANY MUTATIONS IN BOTH DOMINANT AND RECESSIVE ONCOGENES TO POSSESS MALIGNANT PHENOTYPES. SEVERAL GENETIC AND EPIGENETIC CHANGES ARE COMMON TO ALL LUNG CANCER HISTOLOGIC TYPES, WHILE OTHERS APPEAR TO BE CELL TYPE SPECIFIC. HOWEVER, SPECIFIC ROLES OF THE GENES UNDERGOING MUTATIONS AND THE ORDER OF CUMULATIVE MOLECULAR CHANGES THAT LEAD TO THE DEVELOPMENT OF EACH LUNG TUMOR HISTOLOGIC TYPE REMAIN TO BE FULLY ELUCIDATED. RECENT FINDINGS OF MOLECULAR ABNORMALITIES IN NORMAL APPEARING AND PRENEOPLASTIC BRONCHIAL EPITHELIUM FROM PATIENTS WITH LUNG CANCER AND CHRONIC SMOKERS SUGGEST THAT GENETIC CHANGES MAY SERVE AS BIOMARKERS FOR EARLY DIAGNOSIS, RISK ASSESSMENT AND MONITORING RESPONSE TO CHEMOPREVENTION. 2002 18 5290 20 PROSTATE CANCER PREVENTION: AGENT DEVELOPMENT STRATEGIES. DESPITE ADVANCES IN SURGERY, RADIATION, AND MEDICAL THERAPY OVER THE PAST DECADE AND THE WIDESPREAD ADOPTION OF PSA SCREENING, PROSTATE CANCER CONTINUES TO BE THE SECOND LEADING CAUSE OF CANCER DEATH IN MEN IN THE UNITED STATES. INVASIVE CANCER IS THE END RESULT OF CARCINOGENESIS, A CHRONIC PROCESS OCCURRING OVER MANY YEARS DRIVEN BY GENETIC AND EPIGENETIC ALTERATIONS. THE PROTRACTED NATURE OF THIS TRANSFORMATION TO THE MALIGNANT PHENOTYPE PROVIDES AN OPPORTUNITY TO INTERVENE PHARMACOLOGICALLY TO PREVENT, REVERSE, OR DELAY CARCINOGENESIS, I.E. CHEMOPREVENTION. HEREIN, WE DESCRIBE THE UNIQUE FEATURES OF CANCER PREVENTION, AS OPPOSED TO CANCER TREATMENT, AGENT DEVELOPMENT CLINICAL TRIALS, AND PROVIDE A SUMMARY OF THE ONGOING RESEARCH IN THIS FIELD BEING SUPPORTED BY THE NATIONAL CANCER INSTITUTE. 2014 19 2704 17 EXERCISE AND COLORECTAL CANCER: PREVENTION AND MOLECULAR MECHANISMS. EXERCISE AND PHYSICAL ACTIVITY HAVE BEEN SHOWN TO BE STRONGLY ASSOCIATED WITH A DECREASED INCIDENCE RATE OF VARIOUS CHRONIC DISEASES ESPECIALLY NUMEROUS HUMAN MALIGNANCIES. A HUGE NUMBER OF CLINICAL TRIALS AND META-ANALYSIS HAVE DEMONSTRATED THAT EXERCISE IS SIGNIFICANTLY EFFECTIVE IN LOWERING THE RISK OF COLORECTAL CANCER. IN ADDITION, IT IS SUGGESTED AS AN EFFECTIVE THERAPEUTIC MODALITY AGAINST THIS CANCER TYPE. THEREFORE, IN THIS REVIEW, WE WILL REVIEW COMPREHENSIBLY THE EFFECTS OF EXERCISE IN PREVENTING, TREATING, AND ALLEVIATING THE ADVERSE EFFECTS OF CONVENTIONAL THERAPEUTIC OPTIONS IN COLORECTAL CANCER. MOREOVER, THE POSSIBLE MECHANISMS UNDERLYING THE POSITIVE EFFECTS OF EXERCISE AND PHYSICAL ACTIVITY IN COLORECTAL CANCER, INCLUDING REGULATION OF INFLAMMATION, APOPTOSIS, GROWTH FACTOR AXIS, IMMUNITY, EPIGENETIC, ETC. WILL BE ALSO DISCUSSED. 2022 20 2676 25 ETIOPATHOGENESIS OF OVARIAN CANCER. AN INFLAMM-AGING ENTITY? OVARIAN CANCER IS ONE OF THE MOST COMMON GYNECOLOGIC CANCERS AND HAS THE HIGHEST MORTALITY RATE. THE RISK/PROTECTIVE FACTORS OF OVARIAN CANCER SUGGEST THAT ITS ETIOLOGY IS MULTIFACTORIAL. SEVERAL FACTORS ARE INVOLVED IN AGE-RELATED INCREASES IN CARCINOGENESIS, INCLUDING THE ACCUMULATION OF SENESCENT CELLS, INFLAMMAGING (A CHRONIC INFLAMMATORY STATE THAT PERSISTS IN THE ELDERLY), AND IMMUNOSENESCENCE (AGING OF THE IMMUNE SYSTEM) CHANGES ASSOCIATED WITH POOR IMMUNE SURVEILLANCE. AT SITES OF INFLAMMATION, EXPOSURE TO HIGH LEVELS OF INFLAMMATORY MEDIATORS, SUCH AS REACTIVE OXYGEN SPECIES, CYTOKINES, PROSTAGLANDINS, AND GROWTH FACTORS, CONTRIBUTES TO INCREASED CELL DIVISION AND GENETIC AND EPIGENETIC CHANGES. THESE EXPOSURE-INDUCED CHANGES PROMOTE EXCESSIVE CELL PROLIFERATION, INCREASED SURVIVAL, MALIGNANT TRANSFORMATION, AND CANCER DEVELOPMENT. FURTHERMORE, THE PROINFLAMMATORY TUMOR MICROENVIRONMENT CONTRIBUTES TO OVARIAN CANCER METASTASIS AND CHEMORESISTANCE. THIS NARRATIVE REVIEW OF THE LITERATURE WAS CARRIED OUT TO DELINEATE THE POSSIBLE ROLE OF INFLAMMAGING IN THE ETIOPATHOGENESIS OF OVARIAN CANCER DEVELOPMENT. WE DISCUSS THE CURRENT CARCINOGENIC HYPOTHESES, SITES OF ORIGIN, AND ETIOLOGICAL FACTORS OF OVARIAN CANCER. TREATMENT OF INFLAMMATION MAY REPRESENT AN ATTRACTIVE STRATEGY FOR BOTH THE PREVENTION AND THERAPY OF OVARIAN CANCER. 2022