Low glycemic index diet, exercise and vitamin D to reduce breast cancer recurrence (DEDiCa): design of a clinical trial.

BACKGROUND: Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. METHODS: Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. DISCUSSION: DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. TRIAL REGISTRATION: May 11, 2016; NCT02786875 . EUDRACT NUMBER: 2015-005147-14.

Dietary total antioxidant capacity in relation to endometrial cancer risk: a case-control study in Italy.

PURPOSE: To investigate the role of the overall antioxidant activity of diet, we estimated the relation between three dietary indices of total antioxidant capacity (TAC) and endometrial cancer risk METHODS: We analyzed data from an Italian case-control study including 454 women with incident, histologically confirmed endometrial cancer, and 908 frequency-matched controls admitted to the same hospitals as cases for acute non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects' habitual diet. TAC was measured using Italian food composition tables in terms of Ferric-reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and total radical-trapping antioxidant parameter (TRAP). We computed odds ratios (OR) and corresponding 95 % confidence intervals (CIs) using conditional multiple logistic regression models, including terms for recognized endometrial cancer risk factors and total energy intake. RESULTS: TAC was inversely related to endometrial cancer risk with ORs for the highest versus the lowest quartile of 0.69 (95 % CI 0.47-1.00) for FRAP, 0.68 (95 % CI 0.46-0.99) for TEAC, and 0.68 (95 % CI 0.47-0.98) for TRAP. The relations appeared consistent in strata of selected risk factors and decreased when considering TAC without the contribution of coffee. CONCLUSIONS: Our findings suggest a favorable role of a diet high in TAC on endometrial cancer risk, which can be partially driven by coffee consumption.

Coffee, Tea, Cola, and Bladder Cancer Risk: Dose and Time Relationships.

OBJECTIVE: To further analyze the relation between coffee, tea, and energy drinks and bladder cancer risk, considering dose, duration, and other time-related factors. METHODS AND RESULTS: A multicentric case-control study on 690 bladder cancer cases and 665 hospital controls was conducted in Italy between 2003 and 2014. Odds ratios (ORs) for bladder cancer were estimated using multiple logistic regression models. Sex-, age-, and tobacco-adjusted ORs were 1.27 (95% confidence interval [CI] 0.84-1.94) for current drinkers and 1.69 (95% CI 1.05-2.72) for lifetime drinkers of ≥4 cups/day, compared with non- or occasional coffee drinkers. The corresponding ORs for an increment of 1 cup/day were 1.03 (95% CI 0.96-1.11) and 1.07 (95% CI 0.99-1.15). No association was found between bladder cancer risk and duration or age at starting, and no significant heterogeneity was found according to age and sex, although a slight increased risk emerged in never smokers. Decaffeinated coffee, tea, cola, and energy drinks were not related with bladder cancer risk. CONCLUSION: Our study found no significant relation between coffee and bladder cancer risk after accounting for smoking, although the OR was above unity for high lifetime habit. The lack of dose and duration relationships, however, suggests the absence of a causal relation.

Anthropometric, metabolic and molecular determinants of human epidermal growth factor receptor 2 expression in luminal B breast cancer.

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (

Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial.

BACKGROUND: Inositol has been reported to improve insulin sensitivity since it works as a second messenger achieving insulin-like effects on metabolic enzymes. The aim of this study was to evaluate the inositol and alpha lipoic acid combination effectiveness on metabolic syndrome features in postmenopausal women at risk of breast cancer. METHODS: A six-month prospective, randomized placebo-controlled trial was carried out on a total of 155 postmenopausal women affected by metabolic syndrome at risk of breast cancer, the INOSIDEX trial. All women were asked to follow a low-calorie diet and were assigned randomly to daily consumption of a combination of inositol and alpha lipoic acid (77 pts) or placebo (78 pts) for six months. Primary outcomes we wanted to achieve were both reduction of more than 20% of the HOMA-IR index and of triglycerides serum levels. Secondary outcomes expected were both the improvement of high-density lipoprotein cholesterol levels and the reduction of anthropometric features such as body mass index and waist-hip ratio. RESULTS: A significant HOMA-IR reduction of more than 20% was evidenced in 66.7% (P <0.0001) of patients, associated with a serum insulin level decrease in 89.3% (P <0.0000). A decrease in triglycerides was evidenced in 43.2% of patients consuming the supplement (P <0.0001). An increase in HDL cholesterol (48.6%) was found in the group consuming inositol with respect to the placebo group. A reduction in waist circumference and waist-hip ratio was found in the treated group with respect to the placebo group. CONCLUSIONS: Inositol combined with alpha lipoic acid can be used as a dietary supplement in insulin-resistant patients in order to increase their insulin sensitiveness. Daily consumption of inositol combined with alpha lipoic acid has a significant bearing on metabolic syndrome. As metabolic syndrome is considered a modifiable risk factor of breast tumorigenesis, further studies are required to assess whether inositol combined with alpha lipoic acid can be administered as a dietary supplement in breast cancer primary prevention. TRIAL REGISTRATION: Current Controlled Trial ISRCTN74096908.

Vitamin D supplementation and breast cancer prevention: a systematic review and meta-analysis of randomized clinical trials.

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the "Related Article" feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I(2) test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74-1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23-1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54-1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.

Dietary vitamins E and C and prostate cancer risk.

BACKGROUND: The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer. MATERIAL AND METHODS: Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors. RESULTS: Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer. DISCUSSION: The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.

Coffee, decaffeinated coffee, tea intake, and risk of renal cell cancer.

The relation between coffee, decaffeinated coffee, and tea intake and renal cell carcinoma (RCC) risk was analyzed in a case-control study conducted in Italy between 1992 and 2004. Cases were 767 subjects with incident histologically confirmed RCC and controls were 1,534 patients in hospital for acute non neoplastic conditions. Odds ratios (OR) and 95% confidence intervals (CI) for RCC were computed by multiple logistic regression models, conditioned on study center, sex, and age. Coffee intake (mostly espresso and mocha) was not associated with RCC risk, with an OR of 1.02 (95% CI 0.73-1.43) in drinkers of > or = 4 cups/day compared with drinkers of < 1 cup/day. The corresponding ORs were 1.34 (95% CI 0.87-2.07) in men and 0.67 (95% CI 0.38-1.18) in women, 1.91 (95% CI 0.85-4.31) in current smokers and 0.74 (95% CI 0.41-1.31) in never smokers, with no trend in risk with dose. No relation was observed with decaffeinated coffee (OR = 1.38, 95% CI 0.94-2.03 for drinkers compared with nondrinkers) and tea intake (OR = 0.78, 95% CI 0.59-1.05 for drinkers of > or = 1 cup/day compared with nondrinkers). No significant heterogeneity was found for coffee intake across strata of age, education, body mass index, and consumption of sugar. This study, based on a large dataset, provides further evidence that coffee, decaffeinated coffee, and tea consumption are not related to RCC risk.

Food groups and endometrial cancer risk: a case-control study from Italy.

OBJECTIVE: Although several studies have been conducted on the relation between dietary habits and endometrial cancer risk, the evidence for specific food groups is still controversial. STUDY DESIGN: We analyzed data from an Italian case-control study including 454 women with histologically confirmed endometrial cancer and 908 controls admitted to the same hospitals for acute, nonneoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for major potential confounding factors. RESULTS: A significant increase in risk was observed for red meat, with an OR of 2.07 for an increment of 1 serving per day. Inverse associations were observed for coffee (OR, 0.83), cereals (OR, 0.92), and vegetables (OR, 0.83). CONCLUSION: Our results support the existence of a relation between dietary habits and endometrial cancer risk and in particular suggest that a diet rich in red meat and poor in vegetables may have an unfavorable effect.

Allium vegetables intake and endometrial cancer risk.

OBJECTIVE: The potential role of allium vegetables on endometrial cancer risk has been scarcely investigated and the results of previous Chinese studies are not easily applicable to Western populations. Therefore, we evaluated the relationship between onion and garlic intake and endometrial cancer, using data from an Italian case-control study. SETTING: We analysed data from a multi-centre case-control study of 454 endometrial cancer cases and 908 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions. Information was collected by trained interviewers using a validated and reproducible FFQ. Multivariate odds ratios and 95% confidence intervals were obtained after allowance for recognized confounding factors. RESULTS: Compared with non-users, the OR of endometrial cancer for successive categories of onion intake were 0.94 (95% CI 0.72, 1.21) for <2 portions/week and 0.40 (95% CI 0.22, 0.72) for > or =2 portions/week, with a significant inverse trend in risk (P = 0.01). The OR for an increment of one portion (i.e. 80 g) of onions per week was 0.81 (95% CI 0.70, 0.95). For garlic, the OR for successive categories of intake were 0.89 (95% CI 0.68, 1.15) for intermediate use and 0.62 (95% CI 0.42, 0.92) for high use, with a significant inverse trend in risk (P = 0.02). CONCLUSIONS: Our study found a moderate protective role of allium vegetables on the risk of endometrial cancer.

Macronutrients, fatty acids, cholesterol and renal cell cancer risk.

The role of selected macronutrients, fatty acids and cholesterol in the etiology of renal cell carcinoma (RCC) was analyzed using data from a case-control study conducted in 4 Italian areas between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas. Controls were 1,534 subjects admitted for acute, nonneoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of nutrient intake were estimated after allowance for total energy intake and other potential confounding factors. A direct association with RCC was found for starch intake (OR = 1.9 for highest versus lowest quintile of intake; 95% CI: 1.4-2.6, p-value for trend = 0.001), while an inverse association was found for fats from vegetable sources (OR = 0.6; 95% CI: 0.5-0.8; p-value for trend = 0.002), unsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.001). Among polyunsaturated fatty acids, linoleic acid (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0001) and linolenic acid (OR = 0.7; 95% CI: 0.5-1.0; p-value for trend = 0.01) were inversely related to RCC. When 6 major macronutrients were included in the same model, the adverse effect of high intake of starch remained statistically significant, together with the protective effect of polyunsaturated fatty acids. Results were consistent in strata of age, body mass index, treated hypertension, energy intake, stage and family history of RCC.

Onion and garlic intake and the odds of benign prostatic hyperplasia.

OBJECTIVE: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy. METHODS: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake. RESULTS: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata. CONCLUSIONS: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.

Coffee and tea consumption and risk of hepatocellular carcinoma in Italy.

The role of coffee in the aetiology of hepatocellular carcinoma has raised great interest. In Italy, coffee consumption is high, thus allowing the investigation of the topic over a broad range of consumption. A hospital-based case-control study was conducted in Italy in 1999-2002, including 185 incidents, histologically confirmed cases of hepatocellular carcinoma aged 43-84 years. Controls were 412 subjects admitted to the same hospitals' networks for acute, non-neoplastic diseases unrelated to diet. Coffee and tea consumption were assessed using a validated food-frequency questionnaire. Odds ratios (ORs) and corresponding the 95% confidence intervals (CI) were computed using unconditional multiple logistic regression, adjusting for hepatitis viruses seropositivity, alcohol intake, smoking habits and other potential confounding factors. Compared to people who drunk <14 cups/week of coffee, the risk of hepatocellular carcinoma decreased for increasing levels of consumption (OR=0.4, 95% CI: 0.2-1.1 for >or=28 cups/week, p for trend = 0.02). In the present study, inverse relations were observed across strata of hepatitis C and, B virus infections and alcohol drinking. No significant association emerged with consumption of decaffeinated coffee (OR=0.7, 95% CI=0.2-2.5) or tea (OR=1.4, 95% CI=0.8-2.7). The present study supports the hypothesis of a favourable effect of coffee, though not decaffeinated coffee and tea, on the risk on hepatocellular carcinoma.

Olive oil, seed oils and other added fats in relation to ovarian cancer (Italy).

OBJECTIVE: This study investigates the potential role of olive oil and other added fats used for seasoning or cooking on ovarian carcinogenesis. METHODS: We analyzed data from a multicentre case-control study conducted between 1992 and 1999 in Italy, including a total of 1031 incident with a first diagnosis, histologically confirmed epithelial ovarian cancer cases and 2,411 hospital controls with acute, non-malignant and non-gynecological conditions. The subjects' usual diet was investigated through a validated food-frequency questionnaire, including specific questions aimed at assessing added fat intake patterns. RESULTS: After allowance for study centre, year at interview, age, education, parity, oral contraceptive use, and total energy intake, a reduced risk of ovarian cancer was observed for high intake of olive oil (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.50-0.93 for the highest quintile of intake, compared to the lowest one) and for a group of specific seed oils (i.e. sunflower, maize, peanut, and soya) (OR = 0.59, 95% CI 0.46-0.76). No significant associations were observed for mixed seed oils, butter, and margarine. CONCLUSIONS: The present study suggests a favorable effect of olive oil and other vegetable oils on ovarian cancer in this Italian population.