What cancer means and its aetiology

What cancer means and its aetiology

There are many known substances or agents that play an important role in cancer formation these agents are called carcinogenesis which may be either viral carcinogens, physical carcinogens, genetic carcinogens and chemical carcinogens

How cancer formed or what is cancer 

The body is the basic unite of the life, so question how normal cells become cancer cells as we know the body contains millions of cells these normal cells undergo the process of growth ,division  in controlled manner to produce more cells as they need to keep the body healthy when these normal cells become old or damaged they die which called programmed cell death and are replaced by new normal cells but sometimes this normal orderly process goes wrong
as we know also all normal cells in the body have a central nucleus which contains genes made from DNA, this gene control the function of the cell  when this genetic material DNA of the cell become changed or damaged by carcinogenic agents this lead to mutations that affect the normal cell growth and division ,when this occur the cells do not die when they should and new cells form when the body does not need them these abnormal cells not die but continuous to growth in abnormal manner without any control untill form mass called tumor then the cancer can spread or metastasis to other organs
the cancer is a complex process which arise from single cell 
There are many different types of cells in the body ,and many different types of cancer which arise from many different types of cells
What are the causes of cancer
Cancer causes can be divided into main four categories as follow
Viral causes
Physical causes
Genetic causes
Chemical causes
Viral causes of cancer

  There are several human viruses are known to have oncogenic properties, oncogens means  is a gene that has the potential to causes cancer and several have been causally linked to human cancers it is estimated that 15% of all human tumors worldwide are caused by viruses
Viruses may cause or increase the risk of malignancy through several mechanisms  Including direct transformation, expression of oncogenes that interfere with cell-cycle check points or DNA re­pair, expression of cytokines or other growth factors, and alter­ation of the immune system
Oncogenic viruses may be RNA or DNA viruses, Oncogenic RNA viruses are retroviruses and con­tain a reverse transcriptase After the viral infection, the single­ stranded RNA viral genome is transcribed into a double-stranded DNA copy  which is then integrated into the chromosomal DNA of the cell Retroviral infection of the cell is permanent, thus integrated DNA sequences remain in the host chromosome  Oncogenic trans­forming retroviruses carry oncogenes derived from cellular genes
These cellular genes, referred to as proto oncogenes, usually are involved in mitogenic signaling and growth control, and include pro­tein kinase, G proteins, growth factors, and transcription factors
Integration of the provirus upstream of a protooncogene may produce chimeric virus-cell transcripts and recombination during the next round of replication that could lead to incorporation of the cellular gene into the viral genome
Unlike the oncogenes of the RNA viruses, those of the DNA tumor viruses are viral, not cellular in origin

These genes are required for viral replication utilizing the host cell machinery

In permissive hosts, infection with an oncogenic DNA virus may result in a pro­ductive lytic infection, leading to cell death and the release of newly formed viruses
In non permissive cells, the viral DNA can be inte­grated into the cellular chromosomal DNA, and some of the early viral genes can be synthesized persistently,leading to transformation of cells to neoplastic state
Uno-compromised individuals are at elevated risk most patient,s infected with oncogenic viruses do not develop cancer when cancer does develop
It usually occurs several years after the viral infection  It is estimated, for example, that the risk of the hepatocellular carcinoma among hepatitis C virus-infected individuals is 1 to 3 % after 30 years
  There may be synergy between various environmental factors and viruses in carcinogenesis
Factors that predispose to hepatocellular carcinoma
 Among hepatitis C virus-infected include heavy alcohol intake. hepatitis B co-infection and possibly diabetes

some examples for selected viral carcinogens

 Epstein Bar Virus
Related to Burkitts lymphoma ,Hodgkins disease, Immunosuppression related lymphoma, Nasopharyngeal carcinoma
Hepatitis B
 Related to Hepatocellular carcinoma Hepatitis C
  Related to Hepatocellular carcinoma
  Human immunodeficiency virus or AIDS Related to Kaposi,s sarcoma and non hodgkin,s lymphoma
Human papilloma virus type 16 and 18
Related to Cervical and  Anal cancers
 Human T -cell lymphotropic virus
  related to Adult T - cell leukemia and lymphoma

Physical causes of cancer

Physical carcinogenesis can occur through induction of inflamma­tion and cell proliferation over a period of time or through exposure to physical agents that induce DNA damage
Foreign bodies can cause chronic irritation that can expose cells to carcinogenesis by alter environmental agents

In humans it is associated with chronic irritation and inflammation such as
Chronic non healing wounds
 Inflam­matory bowel syndrome have all been associated with an increased risk of cancer  Helicobacter pylori is associated with gastritis and gastric cancer, and thus its carcinogenicity may be considered phys­ical carcinogenesis
The liver fluke Opisthorchis viverrini similarly leads to local inflammation and cholangiocarcinoma
The induction of lung and mesothelial cancers from asbestos fibers and non fibrous particles such as silica are other examples

If foreign-body-induced physical carcinogenesis asbestos and other fibrous minerals are the key determinants of their carcinogenicity Short fibers can be inactivated by phagocyto­sis while long fibers (> 10 um) are cleared less effectively and are encompassed by proliferating epithelial cells
The long fibere support cell proliferation and have been shown   to preferentially induce tumors
 Asbestos-associated biologic effects also may be mediated through reactive oxygen and nitrogen species Further ­ more, an interaction occurs between asbestos and silica and compo­nents of cigarette smoke  Polycyclic aromatic hydrocarbons (PAH) in cigarette smoke are metabolized by epithelial cells and form DNA adducts
 If PAH is coated on asbestos, PAH uptake is increased. Both PAH and asbestos impair lung clearance, potentially increasing
uptake further, Therefore, physical carcinogens may be synergistic with chemical carcinogens.


 Is the best known agent of physical carcinogenesis and is classified as

 Ionizing radiation (x-rays, gamma rays, and alpha and beta particles) or

Non ionizing radiation (UV) The carcinogenic potential of ionizing radiation was recognized soon after Roentgen,s
, a large number­ of radiation-related skin cancers were reported
Long-term follow-up of survivors of the Hiroshima and Nagasaki atom bombs revealed that virtually all tissues exposed to radiation are at risk for cancer.

Radiation can induce a spectrum of DNA lesions that includes

damage to the nucleotide bases, cross-linking, and DNA single- and double-strand breaks (DSBS) Mis repaired DSBs are the principal lesions of importance in the induction of chromosomal abnormal­ities and gene mutations

DSBs in irradiated cells are repaired primarily by a non homologous end-joining process, which is error prone, thus DSBs facilitate the production of chromosomal rear­rangements and other large-scale changes such as chromosomal deletions
It is thought that radiation may initiate cancer by inacti­vating tumor suppressor genes
Activation of oncogenes appears to play a lesser role in radiation carcinogenesis
Although it has been assumed that the initial genetic events induced by radiation are direct mutagenesis from radiation, other indi­rect effects may contribute to carcinogenesis
 For example, radiation induces genomic instability in cells that persists for at least 30 generations after irradiation
 Therefore, even if cells do not acquire mutations at initial irradiation, they remain at risk for developing new mutations for several generations
Moreover, even cells that have not been directly irradiated appear to be at risk, a phenomenon referred to as the bystander effect irradiated cells may secrete cytokines or other factors that increase production of reactive oxy­gen species in bystander cells, or alternatively, the bystander effect may involve cell-cell communication via gap junctions

Non ionizing UV radiation

Is a potent DNA damaging agent and is known to induce skin cancer
Most non­ melanoma human skin cancers are thought to be induced by re­peated exposure to sunlight leading to a series of mutations that allow the cells to escape normal growth control
For example, mu­tations in the res oncogene and in the tumor suppressors p53 and PTCH have been identified in human skin cancers  In most cases, the mutations induced by the UVB spectrum have been localized to pyrimidine-rich sequences, which indicate that these sites are probably the targets for UV-induced DNA damage and subsequent mutation and transformation
 Patients with inherited xeroderma pigmentosum lack one or more DNA-repair pathways, conferring susceptibility to UV-induced cancers, especially on sun-exposed body parts. Patients with ataxia telangiectasia mutated syndrome also have a radiation-sensitive phenotype

  Genetic causes of cancer

One widely held opinion is that cancer is a genetic disease that arises from an accumulation of mutations that leads to the selection of cells with increasingly aggressive behavior

These mutations may lead ei­ther to a gain of function by oncogenes or to a loss of function by tumor suppressor genes
Most mutations in cancer are somatic and are found only in the cancer cells
Most of our information on human cancer genes has been gained from hereditary cancers
 In the case of hereditary cancers, the individual carries a particular germline mutation in every cell
 In the past decade, more than 30 genes for autosomal dominant hereditary cancers have been identified a few of these hereditary cancer genes are oncogenes, but most are tumor suppressor genes,
Though hereditary cancer syndromes are rare, somatic mutations that occur in sporadic cancer have been found to disrupt the cellular pathways altered in heredi­tary cancer syndromes. suggesting that these pathways are critical to normal cell growth, cell cycle and proliferation
What are the criteria may suggest the presence of a hereditary cancer
. Tumor development at a much younger age than usual
. Presence of bilateral disease
. Presence of multiple primary mutiguancies
. Presentation of a cancer in the less affected sex (e.g.,male breast cancer
 Clustering of the same cancer type in relatives
. Cancer associated with other conditions such as mental retardation or pathognomic skin lesions
It is crucial that all surgeons taking care of cancer patients be aware of hereditary cancer syndromes, since a patient's genetic background has significant implications for patient counseling , planing of surgical therapy

Some examples of the more common hereditary cancer syndromes like as
 rb1 Gene and Hereditary Retinoblastoma
   P53 and U-Fraumeni Syndrome
hCHK2 li-fraumeni Syndrome. and Hereditary Breast cancer
BRCA1, BRCA2, and Hereditary Breast-Ovarian
Cancer Syndrome
   APC Gene and Familial Adenomatous Polyposis
   Mismatch Repair Genes and Hereditary Non polyposis Colorectal Cancer
   P16 and Hereditary Malignant Melanoma
  E- Cadherin and Hereditary Diffuse Gastric Cancer

Chemical Causes of cancer
the report that cancer could be caused by environmental factors it found that 60­ to 90% of cancers all! thought to be due to environmental factors
chemicals carcinogens are classified into three groups based on how they contribute to tumour formation
the first group of chemical agents the genotoxins which can initiate carcinogenesis by causing a mutations
the second group the co-carcinogens by themselves can not causes cancer but potentiate carcinogenesis by
enhancing the potency of the genotoxins
the third group tumour promoters enhance tumour formation when given after exposure to genotoxins
some important examples for chemical agents or carcinogens and it is relation to cancer causing
   Aflatoxins related to liver cancer
  Aresnic related to skin cancer
 Benzene related to leukemia
 Benzidine related to bladder cancer
   Berylium related to lung cancer
   Diethylstilbestrol  related to vaginal and cervical clear cell adenocarcinoma
   Estrogen replacement therapy related to endometrial and breast cancers
   tobacco products smokeless related to oral cancer
  Tobacco smoke related to lung cancer oral cancer pharyngeal laryngeal esophageal cancers pancreatic liver renal bladder cervical cancers and leukemia
Coal tar related to skin and scrotal cancers

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