A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women

Exercise levels and preferences in cancer patients: A cross-sectional study

Background: Despite the benefits related to physical exercise, large numbers of cancer patients are not sufficiently active. Methods: To investigate exercise levels and preferences in cancer patients, a cross-sectional study was conducted on a random sample of 392 cancer outpatients who anonymously completed a questionnaire investigating general and medical characteristics, and expressed willingness to participate in exercise programs. Current exercise levels were estimated with the Leisure Score Index (LSI). Results: Most patients (93%) were insufficiently active but 80% declared an interest in exercise programs. Patients preferred oncologist-instructed programs and specified particular exercise needs. Multivariate logistic regression showed that willingness to exercise was associated with education (OR: 1.87; 95% CI: 1.15–3.04 beyond age 14 years vs. up to 14 years) and current physical activity (OR: 1.92; 95% CI: 1.92–3.63 for sweat-inducing activity >2 times/week vs. <1 time/week). Patients given chemotherapy were less inclined to exercise (OR: 0.45; 95% CI: 0.23–0.86) than those who did not. LSI was lower if cancer stage was advanced (β:-0.36; 95% CI: −0.75 to −0.02) than if it was in remission. High LSI was also associated with longer education, lower BMI, and longer time after diagnosis. Conclusion: Cancer patients are insufficiently active but are willing to participate in personalized exercise programs. Information from this survey may help in designing personalized interventions so these patients will achieve sufficient exercise

Dietary patterns and longitudinal change in body mass in European children: a follow-up study on the IDEFICS multicenter cohort

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The influence of outdoor air pollution on cadmium exposure assessment: a cross-sectional population-based Italian study.

The influence of outdoor air pollution on cadmium exposure assessment: a cross-sectional population-based Italian study

Determinants of serum manganese levels in an Italian population.

Manganese (Mn) is both essential and toxic for humans, mainly depending on the total levels and its species. Main sources of exposure include food and air pollution, particularly motorized traffic. We sought to determine the potential influence of these sources on serum total levels of Mn and Mn species. We selected a random sample of municipality residents from an Italian urban municipality, from whom we collected detailed personal information, dietary habits and a blood sample for serum Mn determination. We also assessed outdoor air Mn exposure, by modeling levels of particulate matter 6410 \ub5m (PM10) from motorized traffic at the residence of geocoded subjects. Serum Mn species generally showed higher levels in males and positive correlation with age, while no such differences were found according to smoking habits or use of dietary supplements. Among nutrients, only iron intake showed a relation with Mn [an inverse correlation with Mn\u2011ferritin (Mn\u2011Fer) and a direct one with inorganic\u2011Mn (Inorg\u2011Mn)]. Meat consumption directly correlated and fish and seafood inversely correlated with total Mn, Mn\u2011transferrin (Mn\u2011Tf) and Mn-citrate (Mn-Cit). Fruits and vegetables, including legumes and nuts, generally showed a positive correlation with all Mn species, especially Mn\u2011Cit, and an inverse one with Inorg\u2011Mn. Odds ratios (ORs) of having serum Mn levels above median value increased with increasing PM10 tertiles, with an OR for highest\u2011to\u2011lowest tertile of 7.40 (1.36\u201140.25) in multivariate analysis. Analyses for Mn species did not highlight a clear comparable pattern. In conclusion, our results seem to demonstrate that PM10 exposure positively influences total Mn serum levels, while single Mn species show conflicting results

Dietary total antioxidant capacity and colorectal cancer in the Italian EPIC cohort

Background Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed. Methods We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center. Results Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44\u20130.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19\u20133.66; 3rd tertile 2.48 95%CI: 1.32\u20134.66; P trend 0.007). Intakes of vitamin C, vitamin E, and f-carotene were not significantly associated with colorectal cancer risk. Conclusions Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers

Dietary glycemic index, glycemic load, and cancer risk: Results from the EPIC-Italy study

Abstract Factors linked to glucose metabolism are involved in the etiology of several cancers. High glycemic index (GI) or high glycemic load (GL) diets, which chronically raise postprandial blood glucose, may increase cancer risk by affecting insulin-like growth factor. We prospectively investigated cancer risk and dietary GI/GL in the EPIC-Italy cohort. After a median 14.9 years, 5112 incident cancers and 2460 deaths were identified among 45,148 recruited adults. High GI was associated with increased risk of colon and bladder cancer. High GL was associated with: increased risk of colon cancer; increased risk of diabetes-related cancers; and decreased risk of rectal cancer. High intake of carbohydrate from high GI foods was significantly associated with increased risk of colon and diabetes-related cancers, but decreased risk of stomach cancer; whereas high intake of carbohydrates from low GI foods was associated with reduced colon cancer risk. In a Mediterranean population with high and varied carbohydrate intake, carbohydrates that strongly raise postprandial blood glucose may increase colon and bladder cancer risk, while the quantity of carbohydrate consumed may be involved in diabetes-related cancers. Further studies are needed to confirm the opposing effects of high dietary GL on risks of colon and rectal cancers

Sources of cadmium exposure in an Italian population: a cross-sectional study

Sources of cadmium exposure in an Italian population: a cross-sectional study

MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer : The hOrmone and Diet in the ETiology of breast cancer prospective study

report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk