Innovative epidemiological and genomic studies to identify risk factors of non-Hodgkin lymphoma

Prof. Ora Paltiel, Director, Braun School of Public Health and Community Medicine, and Senior Hematologist Hadassah University Hospital

Non-Hodgkin lymphoma (NHL) is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. The immune system helps fight infections and cancer. NHL may involve one or several lymph nodes or organs such as the liver, brain, or bone marrow. This disease accounts for approximately 3% of the worldwide cancer burden. Unfortunately, in Israel, the incidence of NHL is quite high and has tripled since the last half of the 20th century. As of 2012, Israel also ranked first in the world in NHL incidence rates. Despite decades of intensive research, NHL remains poorly understood, although results of treatment are encouraging and many patients are cured. Patients with any dysregulation of their immune system, including immune deficiency, autoimmune disease or immune suppression due to medications or transplantation are at higher risk of the disease. Knowledge is scarce about other risk factors for the disease and the causes for the increase in NHL cases are also not known. Thus, it is of the utmost important to identify the clinical, environmental, infectious and genetic risk factors for developing NHL.

Prof. Ora Paltiel, trained in both hematology and epidemiology, has undertaken a large scale epidemiological and state-of-the-art genomic study to identify the risk factors for NHL in two unique populations living in the region. This is indeed a unique study since Israelis and Palestinians who have high incidences of NHL represent genetically and culturally diverse populations, yet living in close proximity to each other. Despite sharing the same ecosystem, the two populations differ in terms of lifestyle, health behaviors and medical systems. Prof. Paltiel’s study has uncovered some risk factors common to both populations and other factors unique to each population using data from medical, environmental, genotyping and lifestyle records as well as novel statistical and bioinformatics tools.

It is known that certain types of infections may raise the risk of NHL. However Prof. Paltiel's research raises another hypothesis regarding the association between infection and NHL, that of joint susceptibility. In this and previous population-based studies in Israel and Sweden, Paltiel and colleagues found that infants with infection requiring hospitalization in infancy are at increased risk of developing NHL later in life. She theorizes that genetically determined immune alterations which are related to susceptibility to infection also predispose to contracting NHL in adult life. In the past, babies who acquired serious infections during their first year of life would in general not survive. With the advent of new medical advances to fight infection, these babies are more likely to survive albeit with a weaker immune system which may be either a cause or a result of prior infection. Dr. Paltiel's research has also shown that individuals with autoimmune diseases are also less likely to be cured by the initial standard therapy and they may be ineligible for novel therapies.

The impact of Prof. Paltiel’s studies is to better understand the causes of lymphoma and hence its prevention and to also identify factors related to its treatment and prognosis. This investigation will also provide a research platform for the future study of lymphoma and serve as a bridge to dialogue among nations to combat this increasingly common disease.