Chapter 16 
The Genetics of Cancer  2  --- Cancer Genes

IV.  Types of cancer genes

1.  Oncogenes

Proto-oncogenes are normal versions of genes which promote cell division.

 

Expression at the wrong time or in the wrong cell type leads to cell division and cancer. 

 

Proto-oncogenes are called oncogenes in their mutated form.

 

One copy of an oncogenic mutation is sufficient to promote cell division.

Oncogenes: 
overexpression of a normal function

Viruses integrated next to a proto-oncogene can cause transcription when the virus is transcribed.
 

2.  Philadelphia chromosomes

Translocation of chr 9 to chr 22 fuses the abl oncogene and the bcr region. 

The abl protein is a tyrosine kinase enzyme.

The bcr-abl fusion protein is active for too long leading to extra cell division in white blood cells, a cancer called leukemia.
 

3.  Tumor suppressor genes

Cancer can be caused by loss of genes that inhibit cell division.

 

Tumor suppressor genes normally stop a cell from dividing.

 

Mutations of both copies of a tumor suppressor gene is usually required to allow cell division.

 

4.  p53 coordinates cell cycle regulation

p53 acts as a cell cycle protein which determines if a cell has repaired DNA damage.  If damage cannot be repaired, p53 can induce apoptosis.

 

More that 50% of human cancers involve an abnormal p53 gene.

 

Rare inherited mutations in the p53 gene cause a disease called Li-Fraumeni syndrome in which family members have many different types of cancer at early ages.

5.  BRCA1, a breast cancer susceptibility gene

Within families a mutation in BRCA1 leads to breast cancer susceptibility, inherited as a dominant trait.

One mutation in the BRCA1 gene is inherited.

Tumors in people acquire a second mutation in the normal allele of BRCA1. 

Lack of any functional BRCA1 leads to cell division.

At the level of the cell, BRCA1 acts in a recessive manner.

Complexities in genetic counseling for familial breast cancer

Many mutations are known but not all are associated with disease. (Some are polymorphisms.)

 

Individual with inherited predisposition and individuals with sporadic cancer can be found within the same family.

 

BRCA1 and BRCA2 are not fully penetrant.  Occasionally individuals with a mutation do not develop cancer.

6.  Multiple genes contribute to cancer progression

Colon cancer results from genetic alterations in multiple gene
 

7.  Environment impacts cancer

Exposure to carcinogens

Carcinogens in tobacco smoke are correlated with lung cancer incidence.

 

Exposure to radiation

Burns from overexposure to sunlight can cause skin cancer.

 

Variation in diet

Fatty diets are correlated with increased estrogen and increased breast cancer.

Cruciferous vegetables can lower cancer risk


8.  Methods for evaluating environmental impacts of cancer

 

Population studies compare incidence of a cancer trait among different populations.

 

Case-control studies compare individuals with cancer to healthy individuals matched for characteristics such as age, sex, and ethnic background.

 

Prospective studies follow the outcome of individuals placed in two or more groups who have different treatments, conditions, or procedures. 

Cancer treatments for breast cancer