Cancer Etiology
1 / 76

??? tumor ? ?????????????????????????????????????????????????? ????? benign tumor ? - PowerPoint PPT Presentation

  • Uploaded on

Cancer Etiology 1. Introduction 2. Chemical Factors in Carcinogenesis 3. Physical Factors in Carcinogenesis 4. Viral Oncogenesis 5. Genetic Predisposition. Introduction. 肿瘤( tumor ) 在致瘤因素作用下,细胞基因失去对细胞增殖、分化和死亡的正常调控,导致组织细胞不断增生而形成的新生物。 良性肿瘤( benign tumor ) 恶性肿瘤( malignant tumor ).

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about '??? tumor ? ?????????????????????????????????????????????????? ????? benign tumor ?' - monet

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Tumor benign tumor

Cancer Etiology1. Introduction 2. Chemical Factors in Carcinogenesis 3. Physical Factors in Carcinogenesis4. Viral Oncogenesis5. Genetic Predisposition

Tumor benign tumor




良性肿瘤(benign tumor)

恶性肿瘤(malignant tumor)

Tumor benign tumor

  • 肿瘤发病率和死亡率

  • 2010年国际抗癌联盟(UICC):

  • 2008年全世界1270万新增癌症患者,死亡人数760万。

  • 《2010中国卫生统计年鉴》:

  • 2009年中国恶性肿瘤成为首位死因。

  • 每年新发癌症病人约200万,死亡人数约150万。

  • 肺癌、肝癌、结直肠癌、乳腺癌、膀胱癌死亡率及其构成明显上升。

  • 肺癌成为我国首位恶性肿瘤死亡原因。

Hallmarks of cancer weinberg cell 2000
Hallmarks of cancer(Weinberg, Cell, 2000)

Figure 1. The Hallmarks of Cancer. This illustration encompasses the six hallmark capabilities originally proposed in our 2000 perspective. The past decade has witnessed remarkable progress toward understanding the mechanistic underpinnings of each hallmark. (Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell 2011, 144:646)

Hallmarks of cancer weinberg cell 2011
Hallmarks of cancer(Weinberg, Cell, 2011)

. (Hanahan D, Weinberg RA. Hallmarks of Cancer: The Next Generation. Cell 2011, 144:646)

Tumor benign tumor

  • The Hallmarks of Cancer

  • Self-sufficiency in growth signals

    • Cancer cells do not need stimulation from external signals (in the form of growth factors) to multiply.

  • Insensitivity to anti-growth signals

    • Cancer cells are generally resistant to growth-preventing signals from their neighbours.

  • Tissue invasion and metastasis

    • Cancer cells can break away from their site or organ of origin to invade surrounding tissue and spread (metastasis) to distant body parts.

  • Limitless reproductive potential

    • Non-cancer cells die after a certain number of divisions. Cancer cells escape this limit and are apparently capable of indefinite growth and division (immortality).

  • Sustained angiogenesis

    • Cancer cells appear to be able to kickstart this process, ensuring that such cells receive a continual supply of oxygen and other nutrients.

  • Evading apoptosis

    • Apoptosis is a form of programmed cell death, the mechanism by which cells are programmed to die after a certain number of divisions or in the event they become damaged. Cancer cells characteristically are able to bypass this mechanism.

Tumor benign tumor

  • Deregulated metabolism

  • Most cancer cells use abnormal metabolic pathways to generate energy, a fact appreciated since the early twentieth century with the postulation of the Warburg hypothesis, but only now gaining renewed research interest.

  • Evading the immune system

    • Cancer cells appear to be invisible to the body’s immune system.

  • Unstable DNA

    • Cancer cells generally have severe chromosomal abnormalities, which worsen as the disease progresses.

  • Inflammation

    • Recent discoveries have highlighted the role of local chronic inflammation in inducing many types of cancer.

  • (Hanahan, D.; Weinberg, R. A. (2011). "Hallmarks of Cancer: The Next Generation". Cell144 (5): 646–674. doi:10.1016/j.cell.2011.02.013 )

Chemical carcinogenesis

Chemical Carcinogenesis

  • Multi-stage Theory of Chemical Carcinogenesis

  • Classification of chemical carcinogens

  • Mechanisms of Chemical Carcinogenesis

  • DNA Damage Induced by Ultimate Carcinogens

  • DNA Repair

Multi stage theory of chemical carcinogenesis
Multi-stage Theory of Chemical Carcinogenesis

Initiation-----------Genetic events

Chemical Carcinogens (Direct and Indirect Carcinogens)

Promotion -------Epigenetic events

Tumor promoters

  • Murine skin carcinogenesis model:

    • A single dose of polycyclic aromatic hydrocarbon (PAH, initiator)

    • Repeated doses of croton oil (promoter)

      Malignant conversion

      Progression ------Genetic and epigenetic events



  • Irreversible genetic damage:

    A necessary, but insufficient prerequisite for tumor initiation

  • Activation of proto-oncogene, inactivation of a tumor suppressor gene, and etc



  • Promotion: Selective expansion of initiated cells, which are at risk of further genetic changes and malignant conversion

  • Promoters are usually nonmutagenic, not carcinogenic alone, often do not need metabolic activation, can induce tumor in conjuction with a dose of an initiator that is too low to be carcinogenic alone

  • Chemicals capable of both initiation and promotion are called complete carcinogens: benzo[a]pyrene and 4-aminobiphenyl


Malignant conversion
Malignant conversion

  • The transformation of a preneoplastic cell into that expresses the malignant phenotype

  • Further genetic changes

  • Reversible

  • The further genetic changes may result from infidelity of DNA synthesis

  • May be mediated through the activation of proto-oncogene and inactivation of tumor-suppressor gene



  • The expression of malignant phenotype, the tendency to acquire more aggressive characteristics, Metastasis

  • Propensity for genomic instability and uncontrolled growth

  • Further genetic changes: the activation of proto-oncogenes and the inactivation of tumor-suppressor genes


Tumor benign tumor

  • Activation of proto-oncogenes:

    • Point mutations: ras gene family, hotspots

    • Overexpression:

      • Amplification

      • Translocation

  • Loss of function of tumor-suppressor genes: usually a bimodal fashion

    • Point mutation in one allele

    • Loss of second allele by deletion, recombinational event, or chromosomal nondisjunction


Gene environmental interactions
Gene-environmental interactions

  • The metabolism of xenobiotics by biologic systems

    • Individual variation

    • The competition between activation and detoxication

  • The alteration of genes by xenobiotics


Classification of chemical carcinogens
Classification of chemical carcinogens

1. Based on mechanisms

  • Genotoxic carcinogen (DNA-reactive)

  • Direct-acting:

    intrinsically reactive

    N-methyl-N’-nitro-N-nitrosoguanidine (MNNG),

    methyl methanesulfonate (MMS),

    N-ethyl-N-nitrosourea (ENU), nitrogen and sulfur mustards

  • Indirect-acting:

    require metabolic activation by cellular enzyme to form the DNA-reactive metabolite (members of the cytochrome P450 family)

    benzo[a]pyrene, 2-acetylaminofluorene, benzidine, Aflatoxin B1, B2.


Tumor benign tumor

(2) Epigenetic carcinogens

  • Promotes cancer in ways other than direct DNA damage/ do not change the primary sequence of DNA

  • Alter the expression or repression of certain genes and cellular events related to proliferation and differentiation

  • Promoters, hormone modifying agents, peroxisome proliferators, cytotoxic agents, and immunosuppressors

  • Organochlorine pesticides, [saccharin], estrogen, cyclosporine A, azathioprine


Tumor benign tumor

2. Based on sturcture

(1) Nitrosamines (NA)

MNNG, MMS (direct carcinogen)

(2) Polycyclic aromatic hydrocarbons (PAH)

Benzo(a)pyrene (indirect carcinogen)

(3) Aromatic amines (AA)

2-acetylaminofluorene, benzidine (indirect carcinogen)

(4) Aflatoxin (AF)

(5) Inorganic elements and their compounds: arsenic, chromium,

and nickel are also considered genotoxic agents


Mechanisms of initiation in chemical carcinogenesis
Mechanisms of Initiation in Chemical Carcinogenesis

(1) DNA damages:

Pro-carcinogen metabolic activation (Phase I and II)

Ultimate carcinogen (electrophiles)

Interaction with macromolecules (nucleophiles)

DNA damage, mutations, chromosomal aberrations, or cell death

(2) Epigenetic changes

(3)Activation of oncogenes; inactivation of tumor suppressor genes


Direct chemical carcinogens
Direct Chemical Carcinogens

  • (1) Alkylating agents are electrophilic compounds with affinity for

  • nucleophilic centers in organic macromolecules.

  • [Fu D, Calvo JA, Samson LD. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat Rev Cancer. 2012 Jan 12;12(2):104-20. doi: 10.1038/nrc3185.]

  • (2) These agents can be either monofunctional or bifunctional.

    • ---Monofunctional alkylating agentshave a single reactive group and thus interact covalently with single nucleophilic centers in DNA (although varied).

  • such as MNNG

    • ---Bifunctional alkylating agentshave two reactive groups, and each molecule is potentially able to react with two sites in DNA.

    • Interstrand DNA cross-link: the two sites are on opposite polynucleotide strands;

    • Intrastrand cross-link: on the same polynucleotide chain of a DNA duplex.

    • such as Nitrogen and sulfur mustard, mitomycin,cis-platinum


Tumor benign tumor

---Monofunctional alkylating agents

Numerous potential reaction sites for alkylation have been identified in all four bases of DNA (not all of them have equal reactivity:


MNNG N-Methyl-N-nitroso-N'-nitroguanidine

Indirect chemical carcinogens and their phase i metabolic derivatives
Indirect Chemical Carcinogensand Their Phase I Metabolic derivatives


Tumor benign tumor

BPDE binds DNA covalently, resulting in bulky adduct damage

BPDE intercalates into dsDNA non-covalently, leading to conformational abnormalities

Types of dna damage induced by ultimate carcinogens
Types of DNA Damage Induced by Ultimate Carcinogens

  • DNA Adduct Formation

  • DNA Break

    Single Strand Break

    Double Strand Break

  • DNA Linkage

    DNA-DNA linkage

    DNA-protein Linkage

  • Intercalation

Bulky aromatic-type adducts, Alkylation (small adducts),

Oxidation, Dimerization, Deamination


Repair systems

DNA Repair

Repair systems

  • Direct DNA repair/ Direct reversal :

    • DNA alkyltransferase (O6-alkylguanine-DNA alkyl transferase)

    • One enzyme per lesion

  • Base excision repair (BER)

    • small adducts,

    • overlap with direct repair

    • glycosylase to remove the adducted base


Tumor benign tumor

  • Nucleotide excision repair (NER):

    • involves recognition, preincision, incision, gap-filling, and ligation,

    • large distortions

    • strand specific, the transcribed strand is preferentially repaired

    • xeroderma pigmentosum (XP): NER deficiency

  • Mismatch repair (MMR)

    • transition mispairs are more efficiently repaired (G-T or A-C) than transversion mispairs

    • microenvironment influences efficiency

    • similar to NER

    • involves the excision of large pieces of the DNA


Tumor benign tumor

  • Double-strand breaks (DSBs)

    • homologous recombination

    • non-homologous end joining (NHEJ): DNA-PK

  • Postreplication repair

    • a damage tolerance mechanism

    • occurs in response to replication of DNA on a damaged template

    • the gap

      • either filled through homologous recombination with parental strand

      • or insert an A residue at the single nucleotide gap


Tumor benign tumor

1.DNA damage blocks the progression of the replication fork.

2.PCNA plays a central role in recruiting the TLS polymerases (translesion DNA synthesis) and effecting the polymerase switch from replicative to TLS polymerase (low stringency DNA polymerases).

3. TLS polymerases carry out TLS, either singly or in combination, past different types of DNA damage.

4.Such regulation must ensure that (1) the specialized polymerases act only when needed, and (2) that polymerases act only at the right location in DNA.

5.TLS evolved in mammals as a system that balances gain in survival with a tolerable mutational cost, and that disturbing this balance causes a potentially harmful increase in mutations, which might play a role in carcinogenesis.


Tumor benign tumor

Characteristics of TLS polymerases

  • They operate at low speed, low processivity and with low fidelity.

  • Their active sites adopt a much more open structure than replicative polymerases, they are less stringent and can accommodate altered bases in their active sites.

  • Y-family polymerases lack a 3’-5’ exonuclease activity, which is an integral part of all replicative polymerases and performs a proofreading function.

  • Each Y family polymerase differs in substrate specificity.

  • All the Y-family polymerases are localized in the nucleus, and during S phase,

  • polη, ι, and Rev1 relocate to replication factories with the polymerase sliding

  • clamp PCNA, and other proteins associated with DNA replication.

  • There are three examples of TLS reactions in which a specialized DNA

  • polymerase bypasses its cognate DNA lesion with higher efficiency and higher

  • fidelity than any other polymerase in the cell:

  • ---Polh and the UV light-induced CPD (cyclobutane pyrimidine dimers);

  • ---Polk and benzo[a]pyrene-guanine (major tobacco smoke-induced DNA lesion);

  • ---Polh and cisplatin-GG (an adduct produced by a drug used in cancer chemotherapy).


Tumor benign tumor

1. Polη

  • Polη was discovered as the protein deficient in the variant form of the skin cancer-prone genetic disorder xeroderma pigmentosum (XP).

  • Most XP patients are deficient in the ability to remove UV photoproducts from their DNA by nucleotide excision repair (NER), but about 20% have problems in replicating their DNA after UV irradiation because of defectiveness of polη gene.

  • Polη carrys out TLS past CPD (cyclobutane pyrimidine dimers) photoproducts generated by exposure to sunlight. XP variant cells have an elevated UV-induced mutation frequency.

    2. Polκ

    Polκcan carry out TLS past DNA containing benzo[a] pyrene-guanine adducts.

    3. Rev1

    Rev1 has a restricted DNA polymerase activity that is confined to the incorporation of one or two molecules of dCMP regardless of the nature of the template nucleotide.

  • Rev1 interacts with multiple TLS polymerases, notably Polη, Polκ, Polι, Polλ, and the REV7 (subunit of Polζ).

  • Rev1 protein may be specifically involved in polymerase switching during TLS.

    4. Polι

    5. Polζ is a heterodimer containing the Rev3 catalytic subunit and the Rev7 regulatory subunit.


Cellular responses evoked by dna damaging agents are very complex events
Cellular responses evoked by DNA damaging agents are very complex events

  • Responses may triggered by the signals originated from:

    genomic and mitochondrial DNA damage

    malfunction of signaling molecules

    endoplasmic reticulum stress


  • Networks between different signaling pathways

  • Cellular responses are the comprehensive and integrated consequences


Hormones and the etiology of cancer
Hormones and the etiology of cancer complex events

  • Major carcinogenic consequence of hormone exposure: cell proliferation

  • The emergence of a malignant phenotype depends on a series of somatic mutation

  • Germline mutations may also occur

  • How to get exposure: contraceptives, hormone replacement therapy, or during prevention of miscarriage

  • Epidemiological studies

Hormone related cancer
Hormone-related cancer complex events

  • Estrogen and breast cancer

  • Endometrial cancer: Estrogen replacement therapy

  • Ovarian cancer: follicle stimulating hormone

  • Prostate cancer and androgen

  • Vaginal adenocarcinoma: in utero diethylstilbestrol (DES) exposure

Other hormone related cancers
Other hormone-related cancers complex events

  • Cervical cancer: OC use might increase the risk, still a lot complicating factors

  • Thyroid cancer: the pituitary hormone thyroid stimulating hormone (TSH)

  • Osteosarcoma: incidence associates with the pattern of childhood skeleton growth; and hormonal activity is a primary stimulus for skeleton growth

Physical factors in carcinogenesis
Physical factors complex eventsin carcinogenesis

Physical carcinogens
Physical carcinogens complex events

  • Corpuscular radiations

  • Electromagnetic radiations

  • Ultraviolet lights (UV)

  • Low and high temperatures

  • Mechanical traumas

  • Solid and gel materials

Ionizing radiation ir
Ionizing radiation (IR) complex events

  • Penetrate cells, unaffected by the usual cellular barriers to chemical agents

  • IR: a relatively weak carcinogen and mutagen

  • The initial critical biologic change is damages to DNA

  • It takes place in a matter of the order of a microsecond or less

Electromagnetic fields emf
Electromagnetic fields (EMF) complex events

Remains controversial:

  • Minimal increase in relative risk of brain tumor and leukemia in electric utility workers

  • Also relatively increased risk for acute lymphoblastic leukemia by EMF exposure during pregnancy or postnatally

  • However, some studies lend no support for this proposition

Ultraviolet uv
Ultraviolet (UV) complex events

  • Sunlight and skin cancer

  • Well established for basal and squamous cell cancers

  • Some controversy remains for melanoma

  • Nonmelanoma skin cancers are the most common cancer in the US (45%)

  • Usually occurs at the age of 50 – 60

Sunlight spectrum and wavelength
Sunlight spectrum and wavelength complex events

  • UVA (320-400)

    • photocarcinogenic

    • weakly absorbed in DNA and protein

    • active oxygen and free radicals

  • UVB (290-320)

    • overlaps the upper end of DNA and protein absorption spectra

    • mainly responsible through direct photochemical damage

  • UVC (240-290)

    • not present in ambient sunlight

    • low pressure mercury sterilizing lamps

    • experimental system

Shielding us from the sun
Shielding us from the sun complex events

  • Ozone: shorter than 300 nm cannot reach the earth’s surface

  • UVA and UVB: only a minute portion of the emitted solar wavelengths ( 0.0000001%)

  • Skin:

    • melanin pigment

    • keratin layers

Xeroderma pigmentosum xp
Xeroderma pigmentosum (XP) complex events(着色性干皮病)

  • Autosomal recessive disease, 1/250,000

  • Obligate heterozygotes (parents): asymptomatic

  • Homozygotes: skin and eyes, even neurologic degeneration

  • Onset at 1-2 year of age

  • 2,000 times higher frequency for cancer

  • 30-year reduction in lifespan

Tumor benign tumor

  • 7 complementation groups, with various reduced rates for complex eventsexcision repair

  • An 8th, the XP variant, has a defect in replication of damaged DNA (polymerase h)

  • Groups A and D are very sensitive to UV killing

  • Group C is the largest group, or called the common/classic form, only shows skin disorders, preferentially repairs transcriptionally active genes

Viral oncogenesis
Viral Oncogenesis complex events

  • RNA Oncovirus (Retrovirus)

  • DNA Oncovirus


Rna oncovirus

RNA Oncovirus complex events

  • Retroviruses:

    • ssRNA viruses

    • Reverse transcriptase

    • Oncogenes

  • Rous sarcoma in chickens (RSV): in 1911

  • Human T-cell lymphotropic virus (HTLV-I,II)

  • Human immunodeficiency virus (HIV)

Classification of retrovirus
Classification of retrovirus complex events


Structure of rna oncovirus
Structure of RNA Oncovirus complex events


Genome of rna oncovirus and gene products
Genome of RNA Oncovirus and Gene Products complex events

Genome of Human T-cell Leukemia virus (HTLV)


Life cycle
Life cycle complex events

  • Receptor binding and membrane fusion

  • Internalization and uncoating

  • Reverse transcription of the RNA genome to form double-stranded linear DNA

  • Nuclear entry of the DNA

  • Integration of the linear DNA into host chromosomal DNA to form the provirus

  • Transcription of the provirus to form viral RNAs

Splicing and nuclear export of the RNAs

Translation of the RNAs to form precursor proteins

Assembly of the virion and packaging of the viral RNA genome

Budding and release of the virions

Proteolytic processing of the precursors and maturation of the virions


Tumor benign tumor

Replication of RNA Oncovirus complex events


Mechanisms of oncogenesis induced by rna oncovirus
Mechanisms of Oncogenesis Induced by RNA Oncovirus complex events

  • Transducing Retrovirus


  • cis-Activating Retrovirus


  • trans-Activating Retrovirus

    tax trans-acting x p40tax

    rex repressive expression x p27rex,p21rex


Tumor benign tumor

  • Oncogene transduction complex events

    • Acutely transforming in vivo and in vitro

    • Transform cells by the delivery (transduction) of an oncogene from the host cell (v-onc) to a target cell

    • Cause the formation of polyclonal tumors

    • Most of this group of viruses are replication defective (the requirement of a helper virus)

    • Examples:

      RSV (v-src);

      Abelson murine leukemia virus (v-Abl)


Insertional activation
Insertional activation complex events

  • Long latent periods, Less efficient

  • Do not induce transformation of cells in vitro

  • Usually are replication competent

  • No oncogenes

  • Tumors are usually monoclonal

  • Provirus (LTR) is found within the vincity of a proto-oncogene (c-myc)

  • Examples: lymphoid leukosis virus;


Grow stimulation and two step oncogenesis
Grow stimulation and two-step oncogenesis complex events

  • The defective spleen focus-forming virus (SFFV) and its helper, the Friend murine leukemia virus (Fr-MuLV)

  • Induce a polyclonal erythrocytosis in mice

  • Require the continued viral replication

  • A mutant env protein gp55 of SFFV binds and stimulated the erythropoietin receptor, thus inducing erythroid hyperplasia

  • Fr-MuLV or SFFV integration inactivates p53


Transactivation complex events

  • HTLV-1 and 2

  • Like cis-activation group: replication competent, carries no oncogene, induces monoclonal leukemia, and latent

  • Like transducing group: can immortalize cells in vitro, has no specific integration site

  • Unique 3’ genomic structure: the X region; Encodes at least three proteins: Tax (p40), Rex (p27, p21)

  • Tax is the focus

    • Transactivate the viral LTR, results in a 100- to 200-fold increase in the rate of proviral transcription

    • Transactivate cellular enhancers and promoters, including genes for IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), c-fos, and others.


Immunodeficiency complex events

  • AIDS patients have an extraordinary increased rate of developing high-grade lymphomas and Kaposi’s sarcoma (KS)

  • Probably secondary

  • However, Tat protein of HIV (the transactivating protein) may induce KS-like lesions in mice.


Endogenous retroviruses
Endogenous retroviruses complex events

  • Exo or endo: somatic vs germline

  • 0.5-1% mammalian genome is composed of retroviral proviruses

  • Some properties:

    • Most are defective

    • Great variations between species or within

    • Variable level of expression

    • Generally not pathogenic

    • The potential to induce disease is notable


Dna oncovirus
DNA Oncovirus complex events

Papilloma virus

Polyoma virus


Herpes virus: EB virus

Hepatitis B virus


Mechanism of oncogenesis induced by dna oncovirus
Mechanism of Oncogenesis Induced by DNA Oncovirus complex events

Transforming proteins

1. HPV E6 interact with P53

E7 interact with RB

2. Adenovirus E1a interact with RB


3. Polyoma virus

SV40 Large T interact with RB

Py virus Large and Middle T

Transcription activators

1. EB virus EBNA-2 and LMP

2. HBV p28 X protein


Gene map and function of hpv
Gene Map and Function of HPV complex events

ORF Function

E1 Virus proliferation

E2 Regulation of transcription

E5、E6、E7 Cell transformation

L1、L2 Encoding capsid protein

E4 Encoding late cytosolic protein

E3、E8 Unkown

  • E5: activates growth factor receptor

  • E6: ubiquitin-mediated degradation of p53

  • E7: binds and inactivates unphosphorylated pRb


Genome of adenovirus
Genome of Adenovirus complex events

Transformaing genes:

E1A: Encoding intranuclear 26 and 30 kD phosphorylated proteins

E1B: Encoding a 19 kD protein located in nuclear and plasma membranes


Gene map of polyoma and sv40 virus
Gene Map of Polyoma and SV40 Virus complex events

Transforming Genes

SV40 virus: Large T Polyoma virus: Large and Middle T


Genome of eb virus
Genome of EB Virus complex events

EBNA (EB virus Nuclear Antigen)

EBNA-1 Immortalization of cell

EBNA-2 trans-acting transcription activator

EBNA-3 Function unknown

LP:Leader Protein RNA Processing

LMP: Latent MembraneProtein Activation of NF-κB

TP:Terminal Protein Function unknown


Genome and products of hbv
Genome and Products of HBV complex events

Transforming gene: X gene

X protein activates gene transcription via XRE


Genetic predisposition
Genetic Predisposition complex events

  • Hereditary Cancer

  • Tumor Genetic Susceptibility

    ---Tumor susceptibility genes:

    Cytochrome P450 family, DNA repair genes, Tumor suppressor genes

  • Immunity

  • Hormones and metabolism

  • Psychological factors

  • others


Localization and presumed functions of proteins encoded by inherited cancer genes shown in magenta
Localization and presumed functions of complex eventsproteins encoded by inherited cancer genes (shown in magenta)


Implications for tumor biology and therapy
Implications for Tumor Biology and Therapy complex events

  • Determinants of the Success of anticancer Agents

    Cell cycle checkpoints, DNA repair, and Apoptosis

  • Genetic Regulation of Tumor Cell death in Response to Anticancer Therapy

  • Improving the Therapeutic Ratio by regulation Cell Death and Senescence