The role of H2AX in non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) is a specific type of cancer where an abnormal growth of immune cells produces what is known as a lymphoid tumour. Since the 1970s, NHL has become increasingly common, indicating that lifestyle and environment are likely causative factors. However, certain individuals may also have a genetic make-up that makes them more susceptible. NHL tumours often show a type of DNA damage called a translocation, where two chromosomes are incorrectly joined together. In NHL tumours, translocations are generally found near genes that are important for the development of immune cells. They cause changes in how these genes are regulated (turned on or off), that result in abnormal cell growth. Certain genes are responsible for repairing damaged DNA. If these genes are not functioning properly, DNA breaks will not be repaired and harmful translocations may occur. Previous studies have found that a common DNA sequence change at one of these DNA repair genes, called H2AX, was much more frequent among the NHL patients than unaffected individuals. Individuals who carry this gene variant have twice the risk of NHL as those who do not carry it. Dr. Karla Bretherick is interested in how common genetic variants influence risk for complex diseases. MSFHR has previously funded her graduate training, which involved studying the genetic factors that contribute to premature menopause. Now, she is looking at why individuals with the H2AX gene variant have increased risk of NHL. She will look at how this DNA sequence change affects H2AX gene regulation, modifies protein binding, and affects the ability of the cell to repair DNA damage. Ways to understand, prevent, and avoid NHL and other cancers are of increasing importance for the Canadian healthcare system. Understanding how and why this specific gene variant increases risk for NHL will lead to a better knowledge of how this cancer develops. This information will eventually be useful for identifying new drug targets and therapies for NHL, and may also provide insight into the development of cancers in general.