2 neoplasia.pdf

EPIDEMIOLOGY CANCER GENES GENETIC LESIONS IN CANCER Esr’a Jameel Nsour, MD. Faculty of medicine Al-Balqa’ applied university E-mail: [email protected] 1 EPIDEMIOLOGY Distribution servivetime • Cancer aIncidence prevalence • Environmental Factors • Age and Cancer • Acquired Predisposing Co...

EPIDEMIOLOGY CANCER GENES GENETIC LESIONS IN CANCER Esr’a Jameel Nsour, MD. Faculty of medicine Al-Balqa’ applied university E-mail: [email protected] 1 EPIDEMIOLOGY Distribution servivetime • Cancer aIncidence prevalence • Environmental Factors • Age and Cancer • Acquired Predisposing Conditions • Interactions Between Environmental and Genetic Factors 2 EPIDEMIOLOGY.. Cont’d F Epidu Ji IN Areal to prevent Community cancers 3 EPIDEMIOLOGY.. Cont’d pygmy dhip Not simple association Eid 5k 448 Keiko www.mail 4 Numbers ### • (WHO) reports in 2012: About 14.1 million new cancer cases worldwide leading to 8.2 million deaths. di • (WHO) suspects in 2035 (based on current mortality rates): About 24 million new case and 14.6 million deaths. it 7 estudiesT Retrospy Y Inari c tw 5 a Incidence(risk to develop cancer) Mortality (risk to die from cancer) 3 0 s 6 the end Environmental Factors Is g it's a hands in cancer Development • Environmental exposures appear to be the dominant risk factors for many common cancers, suggesting that a high fraction of cancers are potentially preventable: better • Diet (obesity): related to many types of cancer exersice • Smoking: e.g (lung, mouth, larynx, esophagus, urinary bladder) cancers • Alcohol consumption: e.g (oropharynx, larynx, esophagus, and liver) cancers After serrosis happened • Reproductive history: (low reproduction rate ..increase the exposure to Amo unopposed estrogen stimulation) : breast and endometrial cancers www.amazon.com m Forlongtime • Infectious agents: Human papillomavirus, Helicobacter pylori, Hepatitis B/C 80 FUN Gang t close tohavecausation R email dance adf.is dae 7 w.ms IÉiiT c.is Age and Cancer inaadenocarcenom • The frequency of cancer increases with age (cancer deaths between 55 and 75 years of age) • Major childhood cancers: leukemias, CNS tumors, lymphomas, and softtissue and bone sarcomas. I b osteosarcoma msn.nl 8 Acquired Predisposing Conditions deade Risk is • Acquired conditions that predispose to cancer include disorders associated with: • chronic inflammation • immunodeficiency states • precursor lesions gff HIVpatient thatmaybeMetaled we givecancer higherRisktodevelopcancer inspicalorgans is 9 I control Examples of chronic inflammatory diseases that may predispose to cancer development. Gusto.es mg TLH II Alfons as coloncancer to 10 well Precursor lesions e • Are localized disturbances of epithelial differentiation that are associated with an elevated risk for developing carcinoma. e • Squamous metaplasia and dysplasia of bronchial mucosa( smokers): lung e carcinoma • Leukoplakia of the oral cavity, vulva, and penis: squamous cell carcinoma • Villous adenoma of the colon: colorectal carcinoma • it is important to recognize precursor lesions because their removal or reversal lowers cancer risk. 11 Genetic only? Environmental factors only? • The risk for developing cancer is modified by interactions between environmental exposures and genetic variants. 12 CANCER GENES • Cancer is a disease caused by mutations in • Cancer genes: genes that are recurrently affected by genetic aberrations in cancers and contribute directly to the malignant behavior. • Causative mutations that give rise to cancer genes: • Acquired: (mutations confined to the cancer cells)/ more common te Caused by: • Environmental factors (e.g chemicals, radiation, viruses) • Spontaneous ratifina • Inherited in the germ line (mutations present in every cell in the body)/ less common d Freres normalGenetic µ up 13 CANCER GENES.. Cont’d • Cancer genes fall into one of four major functional classes: 1. Oncogenes 2 5 2. Tumor suppressor genes a 3. Genes that regulate apoptosis 4. Genes that regulate interactions between tumor cells and host cells 14 Oncogenes • Genes that induce a transformed phenotype when expressed in cells by promoting increased cell growth. • oncogenes are mutated or overexpressed versions of protooncogenes (normal cellular genes) mutated give oneself f • Oncogenes encode transcription factors (pro-growth or enhance cell 49 survival). • Oncogenes are dominant genes (single mutated allele is sufficient)toprodua F the upnormality 15 Tumor suppressor genes IFogenes • Genes that normally prevent uncontrolled growth. • Often both normal alleles of tumor suppressor genes must be damaged for transformation to occur. Ressive Genes • Two general groups: • “governors” that act as important brakes on cellular proliferation. 8410 of • “guardians” that are responsible for sensing genomic damage. mutated 16 Could Genes that regulate apoptosis cancet.SI Io3IsupngyYgnene same.si 0 6 8 is • Genes protect against apoptosis (enhance cell survival) : • overexpressed in cancer cells b• Genes promote apoptosis: I • under expressed or functionally inactivated in cancer cells 17 Genes that regulate interactions between tumor cells and host cells stroma B • For example: tea sit • Genes that enhance or inhibit recognition of tumors cells by the host immune system 18 of Genticsabnormalities GENETIC LESIONS IN CANCER offish GM • The genetic changes found in cancers vary from point mutations involving single nucleotides to abnormalities large enough to produce gross changes in chromosome structure • Driver mutations and Passenger mutations • Driver mutations: (Main role)u in Development of tumorcells If • mutations that alter the function of cancer genes and thereby directly contribute to the development or progression of a given cancer. • usually acquired, some times inherited • clustered within cancer genes 19 Ipt • mutations that are neutral and do not affect cellular behavior. • Passenger mutations: (Supportive role) playritment survival the • Always acquired (appear because of the genetic instability that happened during cancer development). • occur at random (so spread throughout the genome) • found mainly in cancers that caused by carcinogen exposure (melanoma and smoking-related lung cancer) fat chemicals viruses 20 Types of acquired driver mutations: spectrum • Point mutations : (single nucleotides substitution) • RAS proto-oncogen point mutation converted to RAS cancer gene – so tumor development • TP53 point mutation cause loss of inhibitory effect --- so tumor development • Gene rearrangements (caused by translocations or inversions) causing overexpression of oncogenes • Burkitt lymphoma : t(8,14) , that leads to overexpression of the MYC gene on chromosome 8 • Follicular lymphoma: t(14, 18) leads to overexpression of the anti-apoptotic gene, BCL2, on chromosome 18 growth 08s • Deletions: frequently affect tumor suppressor genes (e.g RB gene in retinoblastoma and TP53 gene in many tumors) growth • Amplifications: increases the expression of oncogenes (e.g NMYC gene in neuroblastoma and the HER2 gene in breast cancers) 21 Types of acquired driver mutations …Cont’d • Aneuploidy: is the presence of an abnormal number of chromosomes in a cell: _Ifans if • It results from errors of the mitotic checkpoint • (normally: diploidy in somatic cells (46), haploidy in ovum and sperm (23)) ii • It will cause increase the copy number of oncogenes or decrease the copy number of potent tumor suppressor genes • Changes in miRNAs (microRNA is normally present and control cell growth wee and survival): • It will reduce the expression of tumor suppressors or, • It will increase the expression (overexpression) of proto-oncogenes. on • Tumor suppressor genes and DNA repair genes also may be silenced by epigenetic changes , which involve reversible, heritable changes in gene expression that occur not by mutation, but by methylation of the promoter. this caused By 22 mutated 4 lil 3 DNAGE will cause 8h13 herbidly tumors colorectal III I cancer 23