Exposure to certain — although not yet identified — environmental factors particular to Israel may be linked to an increased risk for Hodgkin’s lymphoma, especially to a classic HL subtype called nodular sclerosis, according to the results of a large study conducted in that country.
The study, “Risk of Hodgkin lymphoma according to immigration status and origin: a migrant cohort study of 2.3 million Jewish Israelis,” published in Leukemia and Lymphoma, revealed that people born in Israel have a higher risk of developing the disease, independent of their paternal country of origin.
The incidence of Hodgkin’s lymphoma (HL) in Israel is among the highest in the world, with similar rates in the Jewish and non-Jewish populations. According to the 2012 GLOBOCAN estimates, Israeli men have the second highest age-standardized incidence of HL worldwide, and Israeli women have the world’s highest.
In the last five decades, Israel also experienced a marked increase in HL incidence among Israeli-born Jews of both sexes, with rates among women jumping from 2.01 to 3.36 per 100,000 people, and men from 2.27 to 3.61 per 100,000 people. But the reasons for such increases are not known.
Immigrant populations are a valuable resource for investigating the relative importance of genetic factors as compared to environmental factors in the development of disease. If populations that migrate from low-risk regions to higher-risk ones exhibit increased incidence, environmental factors would appear to be the decisive factors.
Extensive immigration to Israel since its establishment in 1948, and extensive population data over several decades create a rather unique setting for conducting a large-scale migrant cohort study, such as that done by researchers at Hebrew University-Hadassah Braun School of Public Health and Community Medicine.
A team led by Dr. Hagai Levine and Professor Jeremy Kark examined nationwide data collected from 1967 to 2011, which included almost 2.3 million adolescents, ages 16 to 19, with no history of cancer diagnosis. That data was then linked to Israel’s Cancer Registry to obtain the incidence of HL up to 2012.
Of these adolescents, 2,093 eventually developed HL, and the researchers found an association between being born in Israel and Hodgkin’s lymphoma development, particularly nodular sclerosis HL, its most common subtype. This association was independent of paternal country of origin, or of a person’s sex, year of birth, body mass index, height, and socio-demographic characteristics.
Importantly, the lower HL incidence seen in immigrants from Western Asia was not found in their Israeli-born children, suggesting that environmental or lifestyle factors in Israel were responsible for the increase in HL cases, either independently or in association with genetic factors.
“While we still need further studies to identify the specific causes of the high rates of Hodgkin lymphoma among native Israelis, our findings direct us to search for possible environmental causes in Israel and the neighboring countries. These causes could be not only environmental exposures, but also diet, climate, social environment and stress that may be related to chronic regional conflict,” Levine, head of the Environmental Health Track at the Hebrew University-Hadassah, said in a press release.
“There is increasing evidence for developmental origins of health and disease, with different possible mechanisms, including epigenetic changes or endocrine disruption. There is also increasing evidence on the role of prenatal stress in offspring development, including cancer development, especially for hematological malignancies,” he added. “These data suggest that risk of HL (the nodular sclerosis subtype) is possibly increased due to preconception, prenatal or early life exposures to a changing lifestyle and environment and its interaction with susceptibility genes.”