Metabolic Syndrome and Breast Cancer Risk: A Case-Cohort Study Nested in a Multicentre Italian Cohort

Background

Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies – most confined to postmenopausal women – have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.

Methods

We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.

Results

Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).

Conclusions

These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.     

HCC Development Is Associated to Peripheral Insulin Resistance in a Mouse Model of NASH

NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl₄ or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1–3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl₄ groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+CCl₄ treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD.     

Quantitative trait loci pyramiding for fruit quality traits in tomato

Fruit quality is a major focus for most conventional and innovative tomato breeding strategies, with particular attention being paid to fruit antioxidant compounds. Tomatoes represent a major contribution to dietary nutrition worldwide and a reservoir of diverse antioxidant molecules. In a previous study, we identified two Solanum pennellii introgression lines (IL7-3 and IL12-4) harbouring quantitative trait loci (QTL) that increase the content of ascorbic acid (AsA), phenols and soluble solids (degrees Brix; °Bx) in tomato fruit. The purpose of the present work was to pyramid into cultivated varieties the selected QTL for enhanced antioxidant and °Bx content. To better understand the genetic architecture of each QTL, the two ILs were crossed to the recurrent parent M82 (ILH7-3 and ILH12-4) and between them (ILH7-3+12-4). F1 hybrids (ILH7-3+12-4) were then selfed up to obtain F3 progenies in order to stabilize the favourable traits at the homozygous condition. Species-specific molecular markers were identified for each introgressed region and allowed us to select four F2 genotypes carrying both introgressions at the homozygous condition. The F3 double homozygous plants displayed AsA, total phenols and °Bx content significantly higher than M82. Therefore, they may represent suitable genetic material for breeding schemes aiming to increase antioxidant content in tomato fruit.     

Development and bin mapping of strawberry genic-SSRs in diploid <Emphasis Type="Italic">Fragaria</Emphasis> and their transferability across the Rosoideae subfamily

Cultivated strawberry (Fragaria × ananassa) together with other economically important genera such as Rosa (roses) and Rubus (raspberry and blackberry) belongs to the subfamily Rosoideae. There is increasing interest in the development of transferable markers to allow genome comparisons within the Rosaceae family. In this report, 122 new genic microsatellite (SSR) markers have been developed from cultivated strawberry and its diploid ancestor Fragaria vesca. More than 77% of the sequences from which the markers were developed show significant homology to known or predicted proteins and more than 92% were polymorphic among strawberry cultivars, representing valuable markers in transcribed regions of the genome. Sixty-three SSRs were polymorphic in the diploid Fragaria reference population and were bin-mapped together with another five previously reported but unmapped markers. In total, 72 loci were distributed across the seven linkage groups. In addition, the transferability of 174 Fragaria SSRs to the related Rosa and Rubus genera was investigated, ranging from 28.7% for genic-SSRs in rose to 16.1% for genomic-SSRs in raspberry. Among these markers, 33 and 16 were both localized in the diploid Fragaria reference map and cross-amplified in rose and raspberry, respectively. These results indicate that transferability of SSRs across the Rosoideae subfamily is limited. However, we have identified a set of Fragaria markers, polymorphic in the diploid reference population, which cross-amplified in both Rosa and Rubus, which represents a valuable tool for comparative mapping and genetic diversity analyses within the Rosoideae subfamily.     

Convergent dynamics of the juvenile European sea bass gut microbiota induced by poly-β-hydroxybutyrate

Poly-β-hydroxybutyrate (PHB) is a bacterial energy and carbon storage compound which exhibits a controlling effect on the gastrointestinal microbiota. Its beneficial activities for aquaculture have already been shown in terms of increased disease resistance and growth performance in a number of studies. However, the action of PHB on the intestinal microbial community in the treated animals has not yet been studied in depth. In this research, the effects of PHB on the microbiota composition in the intestinal tract of juvenile sea bass were examined. It was found that fish cohabiting in the same tank were on average 87% similar regarding the intestinal microbiota. When subjected to the same treatment and environmental conditions but reared in different tanks, the compositions of the enteric communities diverged. The provision of PHB overruled this tank effect by sustaining a microbial core community in the gut that represented 60% of the total bacterial diversity at the highest PHB level of 10%. The microbial community compositions converged between replicate tanks upon supplementation of PHB and were characterized by high dynamics and increased evenness. The results are discussed in the framework of hypotheses that try to relate the intestinal microbial community composition to the health status of the host organisms.