Molecular Basis of Cancer

The Molecular Basis of Cancer

During the past decades, researchers have made astonishing progress in identifying the causes of cancer at the molelcular level. The term "cancer" refers to more than 100 forms of the disease. Cancer in generic terms, begins when a cell breaks free from the normal restrains on uncontrolled growth and spread which then become more aggressive over time and eventually disrupt the tissues and organs need for the survival of the organism as a whole.

Cancer as a genetic disease
The role of tumor viruses in the causes of cancer
Carcinogens

Cancer as a genetic disease

Scientists have uncovered the process of cancer development from the genetic point of view. Cancers can arise as consequence of accumulating multiple gene mutations in the genome. Mutations in the genes controlling cell growth are responsible for the causes of many major human cancers. The two gene classes acccount for much of the uncontrolled cell proliferation seen in major humans cancers are called proto-oncogenes and tumor suppressor genes. The activities of these two gene classes are optimally balanced under the normal conditions--Proto-oncogenes encourage cell growth whereas tumor suppressor genes inhibit it. Overactivated proto-oncogenes can become what's called carcinogenic oncogenes which drive excessive cell multiplication and cause proliferation. In contrast, inactivated form of tumor suppressor genes lose the inhibitory effect which is crucial to prevent inappropriate growth.

ONCOGENES INVOLVED IN HUMAN CANCER
GENE NAME FUNCTION CANCER INVOLVED

MDM2 Codes for an antagonist of p53(see below) Sarcomas(connective tissue cancer)

Bcl-2 Codes for a protein that blocks cell suicide mechanism B cell lymphomas

c-myc Actiate other growth-promoting genes leudemias, breast, stomach, and lung

Ki-ras Involved in stimulatory signaling pathways Lung, Ovarian, colon, and pancreatic cancers

erb-B2 Codes for the receptor for epidermal growth factor breast, salivary gland and ovarian cancers

**ONCOGENES INVOLVED IN HUMAN CANCER**
GENE NAME	FUNCTION	CANCER INVOLVED
MDM2	Codes for an antagonist of p53(see below)	Sarcomas(connective tissue cancer)
Bcl-2	Codes for a protein that blocks cell suicide mechanism	B cell lymphomas
c-myc	Actiate other growth-promoting genes	leudemias, breast, stomach, and lung
Ki-ras	Involved in stimulatory signaling pathways	Lung, Ovarian, colon, and pancreatic cancers
erb-B2	Codes for the receptor for epidermal growth factor	breast, salivary gland and ovarian cancers

TUMOR SUPPRESSOR GENES INVOLVED IN HUMAN CANCER
GENE NAME FUNCTION CANCER INVOLVED

p53 Can halt cell division and induce abnormal cells to commit suicide. Involved in a wide range of cancers

RB Master brake for the cell cycle. Ritnoblastomas, bone, bladder, lung , and breast

APC Codes for proteins in the cytoplasm, suppress cell growth Colon and stomach cancers

**TUMOR SUPPRESSOR GENES INVOLVED IN HUMAN CANCER**
GENE NAME	FUNCTION	CANCER INVOLVED
p53	Can halt cell division and induce abnormal cells to commit suicide.	Involved in a wide range of cancers
RB	Master brake for the cell cycle.	Ritnoblastomas, bone, bladder, lung , and breast
APC	Codes for proteins in the cytoplasm, suppress cell growth	Colon and stomach cancers

The role of tumor viruses in the causes of cancer

In brief, cancer is caused by chromosomal abberation which lead to uncontrolled cell growth. Alteration in chromosomes can be due to tumor viruses in some rare cases. For example, Burkit's lymphoma is due to recipricol translocation between chromosome #22 and # 9 which leads to uncontrolled expression of cell-growth promoting genes. Human papilloma virus is also found to be responsible for the cause of some cases of uterine and cervical cancers in women. However, the role of tumor viruses in the direct causes of cancer is still controversial. Nevertheless, the discovery of tumor viruses provides insights into the molecular basis of cancer. There are four different ways that turmor viruses can cause tumor:

1. Addition of new oncogenic information to infected cell (DNA viruses)
2. Activation of proto-oncogenes by insertional mutagenesis.
3. Inactivation of tumor suppressor genes.
4. Alteration in transcriptional regulation of cellular genes.

Picture of human papilloma virus

Carcinogens

Tobacco and diet are the top two causes which account for almost two thirds of all cancer deaths. Cancer risks can be reduced by minimizing exposure to known cancer-causing agents, or carcinogens. Many chemical carcinogens can cause mutations by reacting with DNA causing permanent damamge. Enviromental stressors in workplaces are possible sources of these chemical carcinogens.

Carcinogens in the Workplace
AGENT CACER TYPE FREQUENTLY EXPOSED OCCUPATION EXPOSURE OF GENERAL POPULATION

Arsenic Lung, Skin Tanners; oil refinery workers; insecticide and herbicide sprayers Rare

Asbestos Lung Insulation and demoliton workers Uncommon

Benzene Myelogenous leukemia Painters; petrochemical workers Common

Formaldehyde Nose, nasopharynx Hospital and laboratory workers; manufacturer of textiles, garments Rare

Hair dyes Bladder Hairdressers and barbers Uncommon

Ionizing radiation Bone marrow medical technicians Common

Soot Skin Chimney cleaners Uncommon

**Carcinogens in the Workplace**
AGENT	CACER TYPE	FREQUENTLY EXPOSED OCCUPATION	EXPOSURE OF GENERAL POPULATION
Arsenic	Lung, Skin	Tanners; oil refinery workers; insecticide and herbicide sprayers	Rare
Asbestos	Lung	Insulation and demoliton workers	Uncommon
Benzene	Myelogenous leukemia	Painters; petrochemical workers	Common
Formaldehyde	Nose, nasopharynx	Hospital and laboratory workers; manufacturer of textiles, garments	Rare
Hair dyes	Bladder	Hairdressers and barbers	Uncommon
Ionizing radiation	Bone marrow	medical technicians	Common
Soot	Skin	Chimney cleaners	Uncommon

The above information is summarized from the Scientific American's special issue on Cancer, 1996

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