Researchers have found that non-Hodgkin lymphoma is linked with a number of risk factors, but most patients with lymphoma do not have any known risk factors, and the causes of their cancers are unknown. This is complicated by the fact that lymphomas are actually a diverse group of cancers.

Still, scientists have made a lot of progress in understanding how certain changes in DNA can cause normal lymphocytes to become lymphoma cells. Normal human cells grow and function mainly based on the information contained in each cell's chromosomes. Human DNA is packaged in 23 pairs of chromosomes, which are long molecules of DNA in each cell. DNA is the chemical that makes up our genes -- the instructions for how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than how we look.

Some genes contain instructions for controlling when cells grow and divide. Certain genes that speed up cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA. Cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Some people inherit DNA mutations from a parent that increase their risk for cancer. But non-Hodgkin lymphoma is not one of the cancer types often caused by these inherited mutations. In other words, there is no increased risk of lymphoma in the children of patients with lymphoma.

DNA mutations related to non-Hodgkin lymphoma are usually acquired after birth, rather than being inherited. Acquired mutations may result from exposure to radiation, cancer-causing chemicals, or infections, but often these mutations occur for no apparent reason. They seem to happen more often as we age, and lymphomas for the most part are a cancer of older people.

Translocations are a type of DNA change that can cause non-Hodgkin lymphoma to develop. A translocation means that DNA from one chromosome breaks off and becomes attached to a different chromosome. When this happens, oncogenes can be turned on or tumor suppressor genes can be turned off. Some lymphomas tend to have specific chromosomal defects. For example, most cases of follicular lymphoma have a translocation between chromosomes 14 and 18, which results in the turning on of the bcl-2 oncogene. This stops the cell from dying at the right time.

Scientists are learning much about the exact genes involved in lymphoma. This information is being used to develop new and more accurate tests to detect and classify certain types of lymphoma. Hopefully, these discoveries will soon be used in developing new treatments.

Even though researchers have found many of the key DNA changes that cause lymphoma and are beginning to understand how these changes develop in people with certain risk factors, they still do not know why most lymphomas develop in people with no apparent risk factors.

Lymphocytes (the cells from which lymphomas start) are immune system cells, so it's not surprising that changes in the immune system seem to play an important role in many cases of lymphoma.

• People with immune deficiencies (due to inherited conditions, drug treatment, organ transplants, or HIV infection) have a much higher chance of developing lymphoma than people without an immune deficiency.

• People with certain autoimmune diseases (where the immune system constantly attacks a certain part of the body) have an increased risk of getting lymphoma.

• People with certain chronic infections are also at increased risk, probably because the immune system is constantly making new lymphocytes to fight the infection, which increases the chances for mistakes in DNA.

Last Medical Review: 07/17/2009
Last Revised: 07/17/2009