Mailman School of Public Health
The Jerusalem Perinatal Study is a population-based cohort of mothers, fathers and their 92,408 offspring born in 1964?76. Subsets of the cohort may be at risk for cancer through founder mutations in BRCA1, BRCA2, ATM, BLM, APC and other genes known to be prevalent in Ashkenazi Jews. During 1998?2002 we traced 98% of the offspring (median age 30) and 92% of the mothers and linked them to Israel's Population Registry and its Cancer Registry. We found 542 first primary malignancies in offspring and 2516 in mothers, including 1065 cases of breast cancer. "Mizrahi" Jewish women, with ancestries from Iraq, Iran/Afghanistan and other West Asian countries, showed an increased risk of breast cancers, in comparison to "Sephardi" (Moroccan) Jewish women, after controlling for reproductive and social variables. Daughters of Mizrahi women experienced more breast cancer before age 35, and a specific birth defect was observed in their families. Mizrahi sons and daughters experienced more lymphomas. Other familial associations were observed for myeloid leukemia in offspring, and mortality in young adult offspring was predicted by birth weight.
Preeclampsia was a risk factor for cancers of breast, ovary, stomach, lung/larynx and kidney in mothers, as well as for cardiovascular mortality. We found the wives of elderly fathers more at risk for preeclampsia, suggesting that some cases result from de novo mutation in men's spermatogonia, and raising questions about men's susceptibility to cancer in relation to their potential for reproduction.
During the next three years, we will add fathers to the study, tracing and ascertaining cancer incidence in them. We will use the data to test the hypothesis that cancer in men may be related to their wives' reproductive history as reflected in the time taken to conceive, miscarriages, late fetal deaths and birth defects. We will compare cancer incidence in men whose ancestries derive from different geographic areas, focusing especially on differences between Mizrahim and Sephardim, and evaluating effects of socioeconomic variables. We will update the cancer incidence of offspring and mothers, construct family sets and extend the data analyses in breast cancer and in familial cancers.
Project Leader/Principal Investigator
Department of Epidemiology
A I Neugut M Terry
Hebrew University - Hadassah School of Public Health