Overeating, caloric restriction and breast cancer risk by pathologic subtype: the EPIGEICAM study

This study analyzes the association of excessive energy intake and caloric restriction with breast cancer (BC) risk taking into account the individual energy needs of Spanish women. We conducted a multicenter matched case-control study where 973 pairs completed lifestyle and food frequency questionnaires. Expected caloric intake was predicted from a linear regression model in controls, including calories consumed as dependent variable, basal metabolic rate as an offset and physical activity as explanatory. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. The association with BC risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. While premenopausal women that consumed few calories (>20% below predicted) had lower BC risk (OR = 0.36; 95% CI = 0.21–0.63), postmenopausal women with an excessive intake (≥40% above predicted) showed an increased risk (OR = 2.81; 95% CI = 1.65–4.79). For every 20% increase in relative (observed/predicted) caloric intake the risk of hormone receptor positive (p-trend < 0.001) and HER2+ (p-trend = 0.015) tumours increased 13%, being this figure 7% for triple negative tumours. While high energy intake increases BC risk, caloric restriction could be protective. Moderate caloric restriction, in combination with regular physical activity, could be a good strategy for BC prevention

Therapeutic utility of aspirin in the Apc(Min/+) murine model of colon carcinogenesis

BACKGROUND: In recent years it has become evident that nonsteroidal anti-inflammatory drugs, in particular aspirin represent a potential class of cancer chemotherapeutic agents. Despite the wealth of knowledge gained from epidemiological, clinical and animal studies, the effectiveness of aspirin to treat established gastrointestinal cancer has not been determined. The present study examines the ability of aspirin to treat established polyposis in Min/+ mice. METHODS: Min/+ mice with established polyposis were treated orally once daily from 12–16 weeks of age with either drug vehicle or aspirin (25 mg/kg). Upon completion of treatment, the number, location and size of intestinal tumours was determined. Additional variables examined were the number of apoptotic cells within tumours and COX activity. RESULTS: Administration of aspirin for 4 weeks to Min/+ mice produce no effect on tumour number compared to vehicle-treated Min/+ mice (65 ± 8 vs. 63 ± 9, respectively). In addition, aspirin had no effect on tumour size or location. However, aspirin treatment produced a greater than 2-fold (p < 0.05) increase in the number of apoptotic positive cells within tumours and significantly decreased hepatic PGE(2) content. CONCLUSIONS: Aspirin was found to have no effect on tumour number and size when administered to Min/+ mice with established polyposis. The findings in the present study call in to question the utility of aspirin as a stand-alone treatment for established GI cancer. However, aspirin's ability to significantly promote apoptosis may render it suitable for use in combinatorial chemotherapy

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study

10.1038/sj.bjc.6601340British Journal of Cancer8991686-1692BJCA

Nutrition and cancer: A review of the evidence for an anti-cancer diet

It has been estimated that 30–40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake, consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant portions of fruits and vegetables will lower cancer risk. Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane. Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (α-carotene, β-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very beneficial intravenously. Supplementary use of oral digestive enzymes and probiotics also has merit as anticancer dietary measures. When a diet is compiled according to the guidelines here it is likely that there would be at least a 60–70 percent decrease in breast, colorectal, and prostate cancers, and even a 40–50 percent decrease in lung cancer, along with similar reductions in cancers at other sites. Such a diet would be conducive to preventing cancer and would favor recovery from cancer as well

Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype

Influence of life course socioeconomic position on older women's health behaviors: findings from the British Women's Heart and Health Study.

OBJECTIVES: We examined the association between health behaviors and socioeconomic status (SES) in childhood and adult life. METHODS: Self-reported diet, smoking, and physical activity were determined among 3523 women aged 60 to 79 years recruited from general practices in 23 British towns from 1999 through 2001. RESULTS: The most affluent women reported eating more fruit, vegetables, chicken, and fish and less red or processed meat than did less affluent women. Affluent women were less likely to smoke and more likely to exercise. Life course SES did not influence the types of fat, bread, and milk consumed. Adult SES predicted consumption of all foods considered and predicted smoking and physical activity habits independently of childhood SES. Childhood SES predicted fruit and vegetable consumption independently of adult SES and, to a lesser extent, predicted physical activity. Downward social mobility over the life course was associated with poorer diets and reduced physical activity. CONCLUSIONS: Among older women, healthful eating and physical activity were associated with both current and childhood SES. Interventions designed to improve social inequalities in health behaviors should be applied during both childhood and adult life

Energy intake and dietary patterns in childhood and throughout adulthood and mammographic density: results from a British prospective cohort.

OBJECTIVES: To examine the role of energy intake and dietary patterns in childhood and throughout adulthood on subsequent mammographic density. METHODS: Prospective data were available from a cohort of 1161 British women followed up since their birth in 1946. Dietary intakes at age 4 years were determined by 24-hour recalls and during adulthood, average food consumed at ages 36 and 43 years by 5-day food records. Dietary patterns were determined by factor analysis. Associations between energy intake, dietary patterns, and percent breast density were investigated using regression analysis. RESULTS: During adulthood, energy intake was positively associated with percent breast density (adjusted regression coefficient [per SD) (95% CI): 0.12 (0.01, 0.23)]. The effect of the high fat and sugar dietary pattern remained similar when adjusted for total energy intake [0.06 (-0.01, 0.13)]. There was no evidence of an associations for the patterns low fat, high fiber pattern 0.03 (-0.04, 0.11); the alcohol and fish -0.02 (-0.13, 0.17); meat, potatoes, and vegetables -0.03 (-0.10, 0.04). No association was found for dietary pattern at age 4 and percent breast density. CONCLUSIONS: This study supports the hypothesis that overall energy intake during middle life is a determinant of subsequent mammographic breast density measured 15 years later