Publications by authors named "Agostino Bucalo"

6 Publications

  • Page 1 of 1

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

J Natl Cancer Inst 2021 Jul 28. Epub 2021 Jul 28.

Department of Molecular Medicine, University La Sapienza, Rome, Italy.

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.

Methods: 483 BRCA1 and 1,318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were three versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen-receptor (ER) negative (PRSER-) or ER-positive (PRSER+) breast cancer risk.

Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07-1.83) for BRCA1 and 1.33 (95% CI = 1.16-1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for both BRCA1 (OR = 1.73, 95% CI = 1.28-2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34-1.91) carriers. The estimated breast cancer ORs were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.

Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and to inform clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djab147DOI Listing
July 2021

Gut microbiome profile in psoriatic patients treated and untreated with biologic therapy.

J Dermatol 2021 Jun 28;48(6):786-793. Epub 2021 Jan 28.

Unit of Dermatology, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.

There are increasing data about the role of the gut microbiome in various autoimmune diseases, including psoriasis, a chronic inflammatory and immune-mediated disease. Current treatment strategies in psoriasis include immunomodulating biologic agents. A variable response to this type of therapy has been reported in psoriatic patients. A possible effect of biologic therapy on the gut microbiome composition has been suggested, but data are still limited. The aim of this study was to compare the gut microbiome composition between psoriatic patients treated and untreated with biologic drugs in order to identify differences which may highlight the potential impact of the treatment on the gut microbiome. 16S rRNA sequencing and bioinformatic analyses were performed on the fecal samples of 30 psoriatic patients with similar clinicopathological features, 10 of whom were undergoing biologic therapy and 20 not receiving systemic therapy. Alpha and beta diversity significantly differed between the two groups of patients. A reduced bacterial biodiversity in the group of treated patients compared with the group of untreated patients was observed. Differential relative abundances of key gut microbial communities, including Akkermansia muciniphila and Bacteroides plebeius, were identified between the two groups of patients. This study showed that biologic therapy may have an impact on the composition of the gut microbiome of psoriatic patients. Gut microbiome composition could be used as an indicator of response to therapy and the modulation of the microbial composition could help to restore the intestinal symbiosis in psoriatic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1346-8138.15680DOI Listing
June 2021

Paradoxical Psoriasis Induced by Anti-TNFα Treatment: Evaluation of Disease-Specific Clinical and Genetic Markers.

Int J Mol Sci 2020 Oct 23;21(21). Epub 2020 Oct 23.

Clinic of Dermatology Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical-pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the rs1799964 rare allele ( = 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen ()- rs10484554 rare allele ( = 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21217873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660646PMC
October 2020

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.

Anticancer Res 2019 Aug;39(8):4085-4093

Department of Internal Medicine and Medical Specialties, Unit of Dermatology, "Sapienza" University of Rome, Rome, Italy.

Background/aim: The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinical-pathological factors.

Materials And Methods: MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR-211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR.

Results: A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness >1 mm, high Clark level, ulceration and mitotic rate ≥1/mm Conclusion: Our findings point to miR-205-5p as potential biomarker of distant metastases and to miR-145-5p and miR-203-3p as markers of aggressiveness in melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.13566DOI Listing
August 2019

Evaluation of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk.

Endocr Connect 2019 Aug;8(8):1224-1229

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Breast cancer in men is a rare and still poorly characterized disease. Inherited mutations in BRCA1, BRCA2 and PALB2 genes, as well as common polymorphisms, play a role in male breast cancer genetic predisposition. Male breast cancer is considered a hormone-dependent tumor specifically related to hyperestrogenism. Polymorphisms in genes involved in estrogen biosynthesis and metabolism pathways, such as CYP17A1 and CYP1B1, have been associated with breast cancer risk. Here, we aimed to investigate the role of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk. A series of 597 male breast cancer cases and 1022 male controls, recruited within the Italian Multicenter Study on male breast cancer, was genotyped for CYP17A1 rs743572, CYP1B1 rs1056836 and rs1800440 polymorphisms by allelic discrimination real-time PCR with TaqMan probes. Associations with male breast cancer risk were estimated using logistic regression. No statistically significant associations between male breast cancer risk and the three analyzed polymorphisms emerged. Similar results were obtained also when BRCA1/2 mutational status was considered. No significant differences in the distribution of the genotypes according to estrogen receptor status emerged. In conclusion, our study, based on a large series of male breast cancer cases, is likely to exclude a relevant role of CYP17A1 and CYP1B1 polymorphisms in male breast cancer predisposition. Overall, these results add new data to the increasing evidence that polymorphisms in these genes may not be associated with breast cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-19-0225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733362PMC
August 2019

Contribution of Variants to Male Breast Cancer Risk: Results From a Multicenter Study in Italy.

Front Oncol 2018 4;8:583. Epub 2018 Dec 4.

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Inherited mutations in , and, mainly, genes are associated with increased risk of male breast cancer (MBC). Mutations in and genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether germline variants may contribute to MBC susceptibility. To this aim, we screened the entire coding region of in 503 mutation negative MBC cases by multigene panel analysis. Moreover, we genotyped selected variants, including p.Tyr179Cys, p.Gly396Asp, p.Arg245His, p.Gly264Trpfs7, and p.Gln338His, in a total of 560 MBC cases and 1,540 male controls. Biallelic pathogenic variants (p.Tyr179Cys/p.Arg241Trp) were identified in one MBC patient with phenotypic manifestation of adenomatous polyposis. Monoallelic pathogenic variants were identified in 14 (2.5%) MBC patients, in particular, p.Tyr179Cys was detected in seven cases, p.Gly396Asp in five cases, p.Arg245His and p.Gly264Trpfs7 in one case each. The majority of MBC cases with pathogenic variants had family history of cancer including breast, colorectal, and gastric cancers. In the case-control study, an association between the variant p.Tyr179Cys and increased MBC risk emerged by multivariate analysis [odds ratio (OR) = 4.54; 95% confidence interval (CI): 1.17-17.58; = 0.028]. Overall, our study suggests that pathogenic variants may have a role in MBC and, in particular, the p.Tyr179Cys variant may be a low/moderate penetrance risk allele for MBC. Moreover, our results suggest that MBC may be part of the tumor spectrum associated with MAP syndrome, with implication in the clinical management of patients and their relatives. Large-scale collaborative studies are needed to validate these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2018.00583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288482PMC
December 2018
-->