Breast cancer and the brain: a neurodevelopmental hypothesis to explain the opposing effects of caloric deprivation during the Dutch famine of 1944-1945 on breast cancer and its risk factors (original) (raw)
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Breast Cancer Risk After Caloric Restriction During the 1944-1945 Dutch Famine
JNCI Journal of the National Cancer Institute, 2004
Background: Data from animal models suggest that caloric restriction may reduce the risk of breast cancer, although not all dietary regimens produce similar effects. We examined whether caloric restriction imposed as a consequence of the 1944 -1945 Dutch famine reduced the risk of breast cancer in women participating in a Dutch breast cancer screening program. Methods: Between 1983 and 1986, approximately 15 000 women, aged 2 to 33 years during the 1944 -1945 Dutch famine, responded to a questionnaire about their famine experience. A famine exposure score, graded as absent, moderate, or severe exposure, was derived from answers regarding hunger, cold, and weight loss. During follow-up until January 2000, 585 women with incident breast cancer were identified by the regional cancer registry. The relationship between famine exposure and breast cancer risk was assessed by weighted Cox regression models, in which person-years lived for the entire cohort was extrapolated from data from a random sample of 15% of the cohort. Results: Women who were severely exposed to the famine had a statistically significantly higher risk of breast cancer (hazard ratio [HR] ؍ 1.48, 95% confidence interval [CI] ؍ 1.09 to 2.01) than women who were not exposed. Women who were moderately exposed to the famine had a 13% increased risk of breast cancer (HR ؍ 1.13, 95% CI ؍ 0.92 to 1.38; P trend ؍ 0.016). The association between famine exposure and breast cancer risk was stronger for women who were exposed between the ages of 2 and 9 years (severely exposed versus unexposed: HR ؍ 2.01, 95% CI ؍ 0.92 to 4.41) than for women who were exposed at older ages. Conclusions: The risk of breast cancer was increased in women who were severely exposed to a short but severe famine decades earlier. This result is compatible with data from the few animal studies investigating effects of shortterm, transient caloric restriction. [J Natl Cancer Inst 2004; 96:539 -46]
Transient caloric restriction and cancer risk (The Netherlands)
Cancer Causes & Control, 2007
Over the past century, many animal experiments have shown that caloric restriction can reduce the risk of cancer, a finding that proved to be highly reproducible. Many papers have been published on its potential for human health, but until know little evidence is available on its actual effects in humans. In Utrecht, The Netherlands, we have been investigating the effects of the 1944-1945 Dutch famine on breast cancer risk factors and breast cancer risk, and paradoxically the relatively short-term famine seemed to be related to increased breast cancer risk in later life. One of the differences between the famine situation and the large body of evidence from animal experiments is the duration of caloric restriction. Almost all animal experiments investigated sustained caloric restriction and information on the effects of short-term transient caloric restriction is very scarce. A search in the literature identified some animal experiments on shortterm transient caloric restriction and these seemed to be at least supportive to the famine findings. Because caloric restriction in humans for preventive health measures would be mostly short-term, it is important to extend animal research on short-term caloric restriction.
Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth factor axis
International Journal of Cancer, 2004
The insulin-like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin-like growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944-1945 Dutch famine was associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and -2 levels were weakly decreased. These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine.
Cancer Causes and Control, 1996
There are biologic reasons to believe that the period between thdarche and the first full-term pregnancy is a particularly sensitive period in a woman's life regarding the development of breast cancer. In this ecologic study, data provided by the Norwegian Cancer Registry were analyzed to compare risk of breast cancer among women who experienced this sensitive period before, during, or after World War IL An ordinary age-cohort modal and a modd where the cohort was described by exposure by calendar period and sensitivity to this exposure at different ages, were fitted to the data. The incidence of breast cancer was lower than expected among women who experienced puberty during the war. The estimated configuration of the exposure variable showed an increase in exposure up to the start of WWII to twice the level in 1916, dropped by 13 percent during the war, and increased again after the war. The level in 1975 was approximately 2.7 times higher than the levd in 1916. The results indicate that one or more lifestyle factors that changed among adolescent women during the war, influenced their risk of breast cancer. Dietary intake of energy, fat, meat, milk, fish, fresh vegetables, and potatoes, in addition to physical activity level and height, are important factors to consider in relation to breast cancer risk.
Effect of caloric restriction on pre-malignant and malignant stages of mammary carcinogenesis
Carcinogenesis, 1997
CO 80214, USA chemical species (adrenal cortical steroid) that may be 1 To whom correspondence and reprint requests should be addressed involved in mediating the protective effects of energy Caloric restriction has documented beneficial effects on restriction. These data indicate the feasibility of identifying numerous diseases including cancer, yet the mechanism(s) a chemical basis for the protective effect of caloric restricthat accounts for these wide ranging benefits is unknown.
Childhood exposure to the 1944-1945 Dutch famine and subsequent female reproductive function
Human Reproduction, 2005
BACKGROUND: Childhood caloric restriction may lead to permanent changes in the hypothalamo-pituitarygonadal axis, which could lead to impaired female reproductive ability. We assessed the effect of childhood exposure to the 1944-1945 Dutch famine on subsequent female reproductive function. METHODS: This was a population-based cohort study in Utrecht, The Netherlands. Between 1983Between and 1985Between , 6030 women born between 1932Between -1941 were classified by questionnaire according to their famine exposure experiences. Dates of marriage, first and second childbirth, and information on a medical reason for having no children or fewer children than wanted were available from questionnaires, as well as ages and type of menopause. RESULTS: Severe famine exposure during childhood significantly decreased chances of first and second childbirth at any given time after marriage or first childbirth [adjusted hazard ratios (HR) 0.86, 95% confidence interval (CI) 0.76-0.96; and HR 0.87, 95% CI 0.78-0.97, respectively). Risk of a medical reason for having no or fewer children than wanted was increased in the severely exposed (odds ratio 1.88; 95% CI 1.29-2.74), as was the risk of a surgical menopause (HR 1.53; 95% CI 1.27-1.84). CONCLUSIONS: Our findings support the presence of longstanding modest effects of childhood famine exposure on reproductive function in women.
Nutrition, body size, and breast cancer
American Journal of Physical Anthropology, 1985
Human epidemiologic and animal experimental evidence has suggested that excess intake of macronutrients (total calories, protein, fat) and deficient intake of micronutrients (p carotene, selenium) may be associated with increased incidence and decreased survival of breast cancer in women. The overall pattern of evidence, including migrant studies, has further suggested that dietary patterns in early life may be important to the long-term risk of breast cancer. Since cancer is currently thought to be a multistage process with a long latent period, early nutritional patterns which influence childhood growth and development may also influence the adult risk of cancer. Nutrition-mediated factors which may be associated with breast cancer risk include both anthropometric and reproductive variables. Enduring indicators of growth which can be measured in adults (e.g., stature, sitting height, frame size, lean body mass) may be reflective of early nutritional patterns which place women at increased risk of breast cancer. Anthropometric variables which may be related to adult nutritional patterns (e.g., absolute and relative fatness) are also associated with the risk of cancer in defined groups of women. Anthropometry may aid in the study of the relationship between breast cancer and the timing of nutritional excess, growth, menarche, and other risk factors. Other nutrition-related variables which may be associated with breast cancer include breast secretory activity, bowel function, and lactose tolerance. Recognition of the relationships among nutrition, body size, and breast cancer raises a new context for consideration of the adaptiveness of body size in human populations.
The 1944-1945 Dutch Famine and Subsequent Overall Cancer Incidence
Cancer Epidemiology Biomarkers & Prevention, 2005
Caloric restriction seems to be the most potent dietary intervention to protect against a variety of cancers in animals. We investigated whether overall cancer risk is affected in humans after exposure to a brief famine, followed by a period of abundance. We used data of f15,000 women who were exposed at various degrees to the 1944-1945 Dutch famine at ages between 2 and 33 years. Between 1983 and 1986, these women were asked about their individual experiences of famine exposure (, 1,602 new cancer cases were identified by the regional cancer registry. We assessed the relation between famine and total cancer risk by weighted Cox regression models, in which a 15% random sample was used to represent person-years lived in the entire cohort. In these models, we adjusted for potential confounders. Overall cancer risk was increased in women having been severely famine exposed compared with women having been unexposed (hazard ratio, 1.25; 95% confidence interval, 1.01-1.55). Exclusion of breast cancer cases from our analyses showed that this increase in risk was largely driven by the previously reported increase in breast cancer risk: women who were severely exposed to the famine were at a 1.12 (95% confidence interval, 0.87-1.43) times increased risk of non-breast cancer compared with the unexposed. In conclusion, we found no indications that this brief famine has affected overall cancer risk, exclusive of breast cancer. Counteracting increased caloric intake following the famine, however, may have obscured any relation. (Cancer Epidemiol Biomarkers Prev