Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review.

Objective: To evaluate the reproductive outcomes of patients bearing BRCA-1 and BRCA-2 mutations. Methods: In this retrospective observational cohort study, we assessed data from BRCA-1 and BRCA-2 carriers, analyzing demographics, oncological history, and reproductive outcomes. Statistical analysis compared BRCA-1 and BRCA-2 carriers. A thorough review of the literature was carried out. Results: Fifty-eight patients were included. BRCA-1 and BRCA-2 mutations were equally distributed. Eighty-nine pregnancies occurred in our series, hesitated in 73 live births and 19 miscarriages. Mean age at first and last pregnancy was 27.8 ± 4.8 and 31.6 ± 4.8 years old. Thirty-nine patients have had at least one live birth (67.2%). Mean number of live births was 1.9 ± 0.6. Live birth rate (LBR) was 81.1% and miscarriage rate was 32.8%. Spontaneous fertility was unaltered, as evidenced by high LBR. Subgroup analysis revealed no significant differences between BRCA-1 and BRCA-2 carriers. Conclusions: Our results shows that spontaneous reproductive outcomes in BRCA-mutated patients are reassuring. Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact spontaneous fertility negatively. Further research is needed, and individuals with BRCA mutations should consider early family planning and fertility preservation in case of partner absence.

Impact of the systematic introduction of tomosynthesis on breast biopsies: 10 years of results.

Digital Breast Tomosynthesis (DBT) is a cutting-edge technology introduced in recent years as an in-depth analysis of breast cancer diagnostics. Compared with 2D Full-Field Digital Mammography, DBT has demonstrated greater sensitivity and specificity in detecting breast tumors. This work aims to quantitatively evaluate the impact of the systematic introduction of DBT in terms of Biopsy Rate and Positive Predictive Values for the number of biopsies performed (PPV-3). For this purpose, we collected 69,384 mammograms and 7894 biopsies, of which 6484 were Core Biopsies and 1410 were stereotactic Vacuum-assisted Breast Biopsies (VABBs), performed on female patients afferent to the Breast Unit of the Istituto Tumori "Giovanni Paolo II" of Bari from 2012 to 2021, thus, in the period before, during and after the systematic introduction of DBT. Linear regression analysis was then implemented to investigate how the Biopsy Rate had changed over the 10 year screening. The next step was to focus on VABBs, which were generally performed during in-depth examinations of mammogram detected lesions. Finally, three radiologists from the institute's Breast Unit underwent a comparative study to ascertain their performances in terms of breast cancer detection rates before and after the introduction of DBT. As a result, it was demonstrated that both the overall Biopsy Rate and the VABBs Biopsy Rate significantly decreased following the introduction of DBT, with the diagnosis of an equal number of tumors. Besides, no statistically significant differences were observed among the three operators evaluated. In conclusion, this work highlights how the systematic introduction of DBT has significantly impacted the breast cancer diagnostic procedure, by improving the diagnostic quality and thereby reducing needless biopsies, resulting in a consequent reduction in costs.

miRNA deregulation and relationship with metabolic parameters after Mediterranean dietary intervention in BRCA-mutated women.

Background: Breast cancer onset is determined by a genetics-environment interaction. BRCA1/2 gene alterations are often genetically shared in familial context, but also food intake and hormonal assessment seem to influence the lifetime risk of developing this neoplasia. We previously showed the relationship between a six-months Mediterranean dietary intervention and insulin, glucose and estradiol levels in BRCA1/2 carrier subjects. The aim of the present study was to evidence the eventual influence of this dietary intervention on the relationship between circulating miRNA expression and metabolic parameters in presence of BRCA1/2 loss of function variants. Methods: Plasma samples of BRCA-women have been collected at the baseline and at the end of the dietary intervention. Moreover, subjects have been randomized in two groups: dietary intervention and placebo. miRNA profiling and subsequent ddPCR validation have been performed in all the subjects at both time points. Results: ddPCR analysis confirmed that five (miR-185-5p, miR-498, miR-3910, miR-4423 and miR-4445) of seven miRNAs, deregulated in the training cohort, were significantly up-regulated in subjects after dietary intervention compared with the baseline measurement. Interestingly, when we focused on variation of miRNA levels in the two timepoints, it could be observed that miR-4423, miR-4445 and miR-3910 expressions are positively correlated with variation in vitaminD level; whilst miR-185-5p difference in expression is related to HDL cholesterol variation. Conclusions: We highlighted the synergistic effect of a healthy lifestyle and epigenetic regulation in BC through the modulation of specific miRNAs. Different miRNAs have been reported involved in the tumor onset acting as tumor suppressors by targeting tumor-associated genes that are often downregulated.

SARS-CoV-2 Vaccines and Adverse Effects in Gynecology and Obstetrics: The First Italian Retrospective Study.

The most common effects reported by the Italian Medicine Agency following administration of SARS-CoV-2 vaccine are myalgia, soreness to the arm of inoculation, fever, and asthenia. To date, there are no specific and official reports registered by the Italian Medicine Agency on possible alterations of the menstrual cycle, or of the female reproductive system, following the vaccine. Actually, clinical experience showed a spread of transient adverse drug reactions of the menstrual cycle, following the administration of all COVID-19 vaccine types, both mRNA and Adenovirus vectored ones. In this work, we conducted the first retrospective study on Italian patients vaccinated for SARS-CoV-2 in the period between April 2021 and April 2022, to report the onset of menstrual changes after the vaccine in order to understand: etiology, duration of possible adverse effects, and the extent of the phenomenon. We recruited 100 women aged 18-45, vaccinated for SARS-CoV-2, who were asked to complete a questionnaire consisting of 12 multiple choice questions about the effects of the vaccine on the reproductive system. Thirty-seven of them received three doses of the vaccine, while the remaining 63 received two doses. Symptoms such as delayed menstruation and abnormal uterine bleeding (metrorrhagia, menometrorrhagia, and menorrhagia) were generally reported within the first three weeks of vaccination, especially after the second dose, with a percentage of 23% and 77%, respectively. These preliminary data suggest that this problem may be broader and deserving of further investigation in the future.

Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?

BACKGROUND: Recent studies have shown the importance of the microbiota in women's health. Indeed, the persistence of Human Papilloma Virus (HPV)-related lesions in patients with dysbiosis can be the antechamber to cervical cancer. The aim of this study was to evaluate whether long term administration of oral Lactobacillus crispatus can restore eubiosis in women with HPV infections and hence achieve viral clearance. METHODS: In total, 160 women affected by HPV infections were enrolled at the Department of Gynecological Obstetrics of "San Paolo" Hospital, Italy between February 2021 and February 2022. The women were randomly assigned to two groups, one in treatment with oral Lactobacillus crispatus M247 (group 1, n = 80) versus the control group, that hence only in follow-up (Group 2, n = 80). RESULTS: After a median follow-up of 12 months (range 10-30 months), the likelihood of resolving HPV-related cytological anomalies was higher in patients in treatment with the long term oral probiotic (group 1) versus the group that perfom only follow-up (group 2) (60.5% vs. 41.3%, p = 0.05). Total HPV clearance was shown in 9.3% of patients undergoing only follow-up compared to 15.3% of patients in the group taking long term oral Lactobacillus crispatus M247 (p = 0.34). However, the percentage of HPV-negative patients, assessed with the HPV-DNA test, documented at the end of the study period was not significantly different from the control group. CONCLUSIONS: Despite the limitations of our analysis, we found a higher percentage of clearance of PAP-smear abnormalities in patients who took long term oral Lactobacillus crispatus M247 than in the control group. Larger studies are warranted, but we believe that future research should be aimed in this direction. Trial registration This study is retrospectively registered.

Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.

Association between Cervical Microbiota and HPV: Could This Be the Key to Complete Cervical Cancer Eradication?

The heterogeneity of the cervico-vaginal microbiota can be appreciated in various conditions, both pathological and non-pathological, and can vary according to biological and environmental factors. Attempts are still in course to define the interaction and role of the various factors that constitute this community of commensals in immune protection, inflammatory processes, and the onset of precancerous lesions of the cervical epithelium. Despite the many studies on the relationship between microbiota, immunity, and HPV-related cervical tumors, further aspects still need to be probed. In this review article, we will examine the principal characteristics of microorganisms commonly found in cervico-vaginal specimens (i) the factors that notoriously condition the diversity and composition of microbiota, (ii) the role that some families of organisms may play in the onset of HPV-dysplastic lesions and in neoplastic progression, and (iii) possible diagnostic-therapeutic approaches.

Fertility preservation techniques in cervical carcinoma.

ASTRACT: The usefulness of this review is to highlight how a fertility preservation (FP) approach is currently feasible for patients diagnosed with uterine cervical cancer. To this regard, a fertility sparing surgery has just overcome its traditional limits, gained acceptance within the major gynecologic oncology societies thanks to the ability to identify the "ideal" candidates to this conservative treatment. On the other hand, the use of other FPs for oocyte and ovarian cortex cryopreservation is still extremely debated. In fact, the existing risk of tumor spreading during oocyte retrieval necessary for oocyte cryostorage for patients' candidates for neo-adjuvant therapy, as well as the potential hazard of cancer cell dissemination after ovarian tissue replacement in cases of non-squamous type cervical carcinomas should not be underestimated. Therefore, in consideration of the encountered limitations and the need to ensure adequate reproductive health for young uterine cervical cancer survivors, translational research regarding the FP has progressively collected innovative insights into the employment of stemness technology. In this context, the property of ovarian stem cells obtained from the ovarian cortex to generate functional oocytes in women could represent a promising therapeutic alternative to the current procedures for a novel and safer FP approach in cancer survivors.

Late Endocrine and Metabolic Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment-related sequelae has been observed as a counterpart. METHOD: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine-metabolic sequelae, (ii) evaluate the effects of modern therapeutic approaches on incidence or prevalence of late endocrine-metabolic sequelae, and (iii) determine whether there is evidence of follow-up schemes for their screening/early diagnosis in the subset of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors treated at adult age. The MEDLINE, Embase and the Cochrane Library databases were searched for relevant articles published up to October, 2020. The study selection process was conducted by three independent reviewers and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A risk of bias assessment was performed using the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: In the final analysis, eight studies were included, four of which focused on thyroid disease, two on gonadal dysfunction, one on bone disease and one on metabolic syndrome. Hypothyroidism was reported in up to 60% of adult cHL survivors and was frequently recorded even with modern radiotherapy approaches. Menopause occurred in 52-72% of women after chemotherapy. An 86% reduction in vertebral density was reported following R-CHOP-like chemotherapy. Sarcopenia and metabolic syndrome were reported in 37.9% and 60% of patients, respectively. No validated screening protocols were found for the early diagnosis of long-term treatment-related endocrine and metabolic sequelae, thus the authors finally suggest the execution of screening exams according to the risk category which were identified in the epidemiologic studies.

The Impact of Mediterranean Dietary Intervention on Metabolic and Hormonal Parameters According to BRCA1/2 Variant Type.

The female carriers of BRCA1/2 pathogenic variants (mutations) face a high lifetime risk of developing breast and/or ovarian cancer. However, the risk may differ depending on various genetic and non-genetic elements, including metabolic and hormonal factors. We previously showed that a 6-month Mediterranean dietary intervention trial reduced body weight and the levels of insulin-like growth factor I and other metabolic factors in BRCA mutation carriers. We also found that higher baseline levels of glucose and insulin were significantly associated with BRCA loss-of-function (LOF) variants. In this study, we evaluated whether the BRCA mutation type influences in a different way the metabolic and hormonal response to the dietary intervention in 366 female carriers. The LOF variant carriers randomized in the intervention group (IG) showed significantly higher changes in most considered parameters compared to the control group (CG). The nonsynonymous variant carriers in the IG showed similar changes, but none of them were statistically significant. Performing the "delta" analysis of differences (intention-to-treat analysis), we observed that in LOF variant carriers, the reduction of insulin levels was significantly more pronounced that in nonsynonymous variant carriers. These findings suggest that the changes in insulin levels might be modulated by a different response to the dietary intervention mediated by BRCA LOF variants.

Lean Perspectives in an Organizational Change in a Scientific Direction of an Italian Research Institute: Experience of the Cancer Institute of Bari.

Lean management is a relatively new organizational vision transferred from the automotive industry to the healthcare and administrative sector based on analyzing a production process to emphasize value and reduce waste. This approach is particularly interesting in a historical moment of cuts and scarcity of economic resources and could represent a low-cost organizational solution in many production companies. In this work, we analyzed the presentation and the initial management of current ministerial research projects up to the approval by the Scientific Directorate of an Italian research institute. Furthermore, the initial mode in 2021 ("as is") and the potential mode ("to be") according to a Lean model are studied, according to the current barriers highlighted by the final users of the process and carrying out some perspective analyses with some reference indicators.

The Impact of Healthy Lifestyles on Late Sequelae in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors. A Systematic Review by the Fondazione Italiana Linfomi.

BACKGROUND: In recent years, the scientific community has been paying ever more attention to the promotion of lifestyles aimed at the prevention of late toxicities related to anti-cancer treatments. METHODS: Fondazione Italiana Linfomi (FIL) researchers conducted a systematic review in order to evaluate the evidence in favor of the promotion of lifestyles aimed at the prevention of the main sequelae of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) in survivors treated at adulthood with first-line or second-line therapy, including autologous stem cell transplants (ASCTs). Pubmed, Embase and Cochrane Library were searched up to December 2020. RESULTS: Seven studies were ultimately included in this systematic review; some of them were eligible for multiple PICOS. The majority of the studies emerged from data extraction regarding cHL; less evidence resulted for DLBCL survivors. Five studies in favor of physical activity provided consistent data for a reduction of the cardiovascular risk in cHL and also in survivors who underwent ASCT. A beneficial effect of physical activity in reducing chronic fatigue was found. Being overweight was associated with a higher risk of coronary heart disease in cHL survivors in one of the two eligible studies. Studies aiming to evaluate the impact of the Mediterranean diet on late toxicities and secondary cancers were lacking. Tailored survivorship care plans (SCP) seemed to represent an optimal tool to guide the follow-up and promote healthier lifestyles in the one eligible study. Thus, promotion of healthy lifestyles and empowering of lymphoma survivors should be implemented through structured models. The study also brought to light numerous areas of future clinical research.

18F-FDG PET/CT Cannot Substitute Endoscopy in the Staging of Gastrointestinal Involvement in Mantle Cell Lymphoma. A Retrospective Multi-Center Cohort Analysis.

The detection of gastrointestinal (GI) involvement in Mantle Cell Lymphoma is often underestimated and may have an impact on outcome and clinical management. We aimed to evaluate whether baseline 18F-FDG PET/CT presents comparable results to endoscopic biopsy in the diagnosis of GI localizations. In our retrospective cohort of 79 patients, sensitivity and specificity of 18F-FDG PET/CT were low for the stomach, with a fair concordance (k = 0.32), while higher concordance with pathologic results (k = 0.65) was detected in the colorectal tract. Thus, gastric biopsy remains helpful in the staging of MCL despite 18F-FDG PET/CT, while colonoscopy could be omitted in asymptomatic patients. The validation of our data in prospective cohorts is desirable.

Lifestyle Characteristics in Women Carriers of BRCA Mutations: Results From an Italian Trial Cohort.

BACKGROUND: Women with deleterious mutations in BRCA1/2 have a high lifetime penetrance of developing breast cancer and/or ovarian cancer. Genetic and/or environmental factors may influence BRCA penetrance, and identifying modifiable exposures might be valuable for prevention. PATIENTS AND METHODS: We implemented a multicenter prospective 2-arm (1:1) randomized controlled trial to investigate whether a Mediterranean dietary intervention with moderate protein restriction would reduce potential modulators of BRCA penetrance such as insulin-like growth factor 1 (IGF-1), body weight, and metabolic risk factors. We studied the baseline characteristics of women with BRCA-positive disease who joined the trial cohort, focusing on the relationships between selected lifestyle exposures, metabolic/anthropometric parameters, and BRCA-related cancer. RESULTS: A total of 502 women (304 with a previous diagnosis of breast cancer and/or ovarian cancer and 198 unaffected) with deleterious BRCA mutations, with or without a previous cancer, aged 18 to 70 years and without metastases were included. Late age at menarche and pregnancy were negatively associated with BRCA-related cancer, especially in women with BRCA1-positive disease. Higher fat mass and the presence of 4 or 5 metabolic risk factors were significantly associated with BRCA-related cancer (hazard ratio, 1.87, 95% confidence interval, 1.21-2.88; and hazard ratio, 1.87, 95% confidence interval, 1.11-3.19, respectively), with greater effect in BRCA2-positive women. CONCLUSIONS: Our findings confirm previous observations about reproductive factors in women with BRCA disease and suggest a potential impact of metabolic factors in BRCA-related cancer. The prospective follow-up of the trial cohort will enable us to study the environmental modulators of BRCA penetrance and their impact in relation to the history of BRCA-related cancer. [ClinicalTrials.gov NCT03066856].

A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial.

Background: Women carriers of BRCA1/2 mutations face a high lifetime risk (penetrance) of developing breast and/or ovarian cancer. Insulin-like growth factor I (IGF-I), body weight and markers of insulin resistance affect BRCA penetrance. We conducted a multicenter prospective two-armed (1:1) randomized controlled trial (NCT03066856) to investigate whether a Mediterranean dietary intervention with moderate protein restriction reduces IGF-I and other metabolic modulators of BRCA penetrance. Methods: BRCA carriers, with or without a previous cancer, aged 18-70 years and without metastases were randomly assigned to an active dietary intervention group (IG) or to a control group (CG). The primary endpoint of the intervention was the IGF-I reduction. Results: 416 women (216 in the IG and 200 in the CG) concluded the six-month dietary intervention. The IG showed significantly lowered serum levels of IGF-I (-11.3 ng/mL versus -1.3 ng/mL, p = 0.02), weight (-1.5 Kg versus -0.5 Kg, p < 0.001), waist circumference (-2 cm versus -0.7 cm, p = 0.01), hip circumference (-1.6 cm versus -0.5 cm, p = 0.01), total cholesterol (-10.2 mg/dL versus -3.6 mg/dL, p = 0.04) and triglycerides (-8.7 mg/dL versus + 5.5 mg/dL, p = 0.01) with respect to the CG. Conclusions: A Mediterranean dietary intervention with moderate protein restriction is effective in reducing IGF-I and other potential modulators of BRCA penetrance.

BRCA1/2 Variants and Metabolic Factors: Results From a Cohort of Italian Female Carriers.

Women carriers of pathogenic variants (mutations) in the BRCA1/2 genes face a high lifetime risk of developing breast cancer (BC) and/or ovarian cancer (OC). However, metabolic factors may influence BRCA penetrance. We studied the association of metabolic factors with BRCA1/2 variants and the risk effect of metabolic exposures in relation to the position of the mutations within the BRCA1/2. Overall, 438 women carriers of BRCA1/2 mutations, aged 18-70, with or without a previous diagnosis of BC/OC and without metastases, who joined our randomized dietary trial, were included in the study. The pathogenic variants were divided, according to their predicted effect, into loss of function (LOF) and nonsynonymous variants. The association between metabolic exposures and variants were analyzed by a logistic regression model. LOF variant carriers showed higher levels of metabolic parameters compared to carriers of nonsynonymous variants. LOF variant carriers had significantly higher levels of plasma glucose and serum insulin than nonsynonymous variant carriers (p = 0.03 and p < 0.001, respectively). This study suggests that higher insulin levels are significantly associated with LOF variants. Further investigations are required to explore the association of metabolic factors with LOF variants and the mechanisms by which these factors may affect BRCA-related cancer risk.

Germinal ovarian tumors in reproductive age women: Fertility-sparing and outcome.

MOGCTs (malignant ovarian germ cell tumors) are rare tumors that mainly affect patients of reproductive age. The aim of this study was to evaluate the fertility and survival outcomes in young women with MOCGTs treated with fertility-sparing surgery (FSS).From 2000 to 2018, data from 28 patients of reproductive age with a diagnosis of MOGCT at the University of Bari were collected. Most received FSS, and in patients treated conservatively, the reproductive outcome and survival were investigated. Data of patient demographics, clinical presentation, oncology marker dosage, staging, type of surgery, histological examination, survival, and reproductive outcome were collected from hospital and office charts. All informed consent was obtained from all patients. The median age was 24 (range: 9-45 years). The majority of the patients had stage IIIC. Twenty-four woman received FSS consisting of unilateral ovariectomy and omentectomy, whereas only 4 women, based on their stage (IIIC), received a radical surgery (hysterectomy with bilateral adnexectomy, lymphadenectomy, and omentectomy). Our study shows that FSS in MOGCTs can produce good results both on reproductive outcomes and on survival. Indeed, in our group, there was only 1 case of exitus as result of recurrence. Furthermore, patients after FSS maintained normal ovarian function and 5 of 5 women who tried to get pregnant succeeded spontaneously. The median follow-up was 90 months (range 3-159).Conservative surgery for MOGCTs should be considered for women of reproductive age who wish to preserve fertility.

Anticancer Effects of Nutraceuticals in the Mediterranean Diet: An Epigenetic Diet Model.

Epidemiological and clinical studies support the association between nutrition and development or progression of different malignancies such as colon, breast, and prostate cancer, defining these tumors as diet-associated cancer. The Mediterranean diet shows inverse associations with metabolic diseases, cardiovascular pathologies and various types of cancer. Many bioactive nutrients of the Mediterranean diet have been identified as factors protective against these types of pathologies. The epigenome has been identified as the primary goal of modulations in gene expression related to these molecular nutrients. In fact, they can modify the epigenome and can be incorporated into the 'epigenetic diet', which translates into a diet regimen that can be used therapeutically for health or preventative purposes. Most epigenetic changes are influenced by lifestyle and nutrition. Epigenetic therapy is a new area for the development of nutraceuticals whose absence of toxicity can represent a valid asset in cancer prevention strategies. Recent advances in understanding the mechanisms of nutrigenomics, nutrigenetics and nutraceuticals have led to the identification of superfoods capable of favorably conditioning gene expression. In this review, we highlight the importance of nutraceuticals present in the Mediterranean diet as epigenetic modifiers both in the mechanisms of tumor onset and as protective agents.

The Role of Circulating Adiponectin and SNP276G>T at ADIPOQ Gene in BRCA-mutant Women.

BACKGROUND: Environmental factors may influence the lifetime risk of cancer (penetrance) in women with a BRCA mutation. MATERIALS AND METHODS: In 89 BRCA-mutant women, affected or unaffected by breast/ovarian cancer, we explored serum levels of adipokines and their relation with the polymorphism SNP276G>T as modulators of BRCA penetrance. RESULTS: Affected women had significantly lower adiponectin than healthy women. Affected women with rs1501299 TT had significantly lower adiponectin and higher leptin than GT and GG genotypes. GT genotype was significantly associated with the disease status [odds ratio (OR)=3.24, 95% confidence interval (95% CI)=1.03-10.17]. Women in the lower tertile of serum adiponectin had a RR of BRCA-associated cancer of 2.80, 95% CI=1.1-7.1 (p for trend=0.03) compared with women in the higher tertile. CONCLUSION: In the SNP rs1501299 the T allele was significantly associated with lower serum levels of adiponectin in affected women, suggesting that the T allele might be related to cancer.

Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions.

BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production. AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract. METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure. RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroides distasonis, Clostridium clostridioforme and Pediococcus pentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotella melaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 ± 0.27 mg/24 hrs vs. 21.25 ± 4.3 mg/24 hrs, respectively, p = 1.12 × 10-6). CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions.