Cancer in israeli holocaust survivors: The impact of famine?

Experimental caloric restriction (CR) in laboratory animals extends longevity and profoundly reduces the risk for age-related diseases such as cancer, cardiovascular disease and type II diabetes mellitus. Data on CR in humans are largely derived from wartime under-nutrition (WU) experiences, and the long-term consequences associated with this exposure are not always in line with those expected based on animal studies. Jewish Holocaust survivors were exposed to extreme under-nutrition during World War II (WWII) for extended time periods. In this chapter we will describe in detail two Israeli studies that explored cancer risk in Jewish Holocaust survivors. The first, a retrospective cohort, referred to overall cancer incidence and used a proxy for the exposure, which was defined as being in Europe during WWII. The second, a population-based case-control study, focused on breast cancer and used an individualized, cumulative, measurement tool to assess WWII-related under-nutrition. Both studies disclosed higher cancer risk in those more exposed. The results of the retrospective cohort indicated that overall cancer rates, as well as breast, colorectal and lung carcinoma, were higher in those living in Europe through WWII and the younger the age at exposure, the higher the risk. In the case-control study, breast cancer risk was higher in women exposed to more severe WU, with age at exposure as an independent predictor: the younger the age, the higher the risk. These studies are in accordance with some previous studies on non-Jewish WWII survivors. Under-nutrition is suspected to be an etiologic factor in this association. However, other explanations, such as post-traumatic stress disorder (PTSD) and interactions between the various exposures, cannot be ruled out. In conclusion, the Holocaust studies and the other WU studies in humans disclose associations with higher cancer risk, in contrast to caloric restriction studies in laboratory animals which show lower cancer risks. Therefore caution is needed when extrapolating findings from animal studies into human subjects. In the particular case of Jewish Holocaust survivors, they seem to form a high risk group for cancer, especially breast, colorectal and lung cancer. WU may play an important etiologic role. These observations have direct impact on the health of Holocaust survivors in Israel and elsewhere, and on their caregivers' approach and policy regarding cancer screening. Moreover, these findings are of relevance not only to WWII survivors, but to other communities that had been or are exposed to severe - but transient - under-nutrition.