The Israeli Breast‐Cancer Anomalya

With a few exceptions, age-adjusted breast cancer mortality rates continued to rise in countries throughout the world during the decade 1976-1986.'A tenet of biological research is to regard the exception, in the hope that it may help to explain the rule.In the present context, Israel is exceptional twice over: First, while the nations of the world demonstrate an impressive correlation between per capita fat intake and ageadjusted breast cancer mortality rates, Israel, by virtue of its relatively high breast cancer rates, has stood far out from the pack.Israel is secondly exceptional in thatdespite continual increases during that decade in a number of key breast cancer risk factors and a decrease in acknowledged protective factors-overall, national ageadjusted breast cancer mortalityrates droppedbynearly8% between 1976 and 1986.'This paper examines these breast cancer trends over time and considers whether they may be related to changes in pesticide contamination of milk in Israel.We see in FIGURE 1 that the breast cancer mortality rate in Israel among premenopausal women was about double what it was forothercountrieswith comparable levels of fat consumption.This is all the more remarkable when we note that, worldwide, the great intercountry rate differences tend to appear in the postmenopausal comparisons.'*'An anomaly in the rates for the younger women, therefore, would suggest the influence of an especially potent environmental factor having aselectively greater effect in younger cohorts.Rose, Boyer, and Wynder, on the other hand, feel that population heterogeneity may be the explanation?Over the years, epidemiological and experimental studies have identified a number of putatively causal or protective facto rsf orcancer of the breast!>These include ages at menarche, menopause, and first birth: diet35 (especially fat6" and fiber'.''content), obesity,l1.l2alcohol intake,?14 and even exercise.lsThe thread that links all these factors together runs through the metabolism of estrogen and through the terminal enzymes of the microsomal and mitochondria1 mixed-function-oxidase, or monooxygenase, electron-transport chains: the cytochromes P450.This superfamily of enzymes is involved in the oxidative metabolism of a host of endogenous and xenobiotic substrates including steroids, fatty acids, leukotrienes, prostaglandins, and plant metabolites.'"18Estrogen, for its part, seems to be virtually essential for the initiation of mammary gland tumors in animals and h~rnans;~~'~~'its role in promotion has also been d e m ~n s t r a t e d .' ~* ~~~~* Consider some of the factors noted above as they relate to estrogen and the cytochromes P450.Clearly, ages at menarche, menopause, and first birth are directly related to the hypothesized opening and closing of the "estrogen window."20Increased fat content of the diet has recently been shown to increase dramatically the potential