0000000000099821
AUTHOR
Ines Zanna
Additional file 5: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Pathology of invasive BRCA1 female and male breast tumours and ORs in predicting male BRCA1 mutation carrier status. (DOCX 19 kb)
Contribution of MUTYH variants to male breast cancer risk: results from a multicenter study in Italy
Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 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. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH 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 MUTYH germline v…
A possible role of FANCM mutations in male breast cancer susceptibility: Results from a multicenter study in Italy
Abstract Introduction Breast cancer (BC) in men is a rare disease, whose etiology appears to be associated with genetic factors. Inherited mutations in BRCA1/2 genes account for about 10–15% of all cases. FANCM, functionally linked to BRCA1/2, has been suggested as a novel BC susceptibility gene. Our aim was to test if FANCM germline mutations could further explain male BC (MBC) susceptibility. Methods We screened the entire coding region of FANCM in 286 MBCs by a multi-gene panel analysis, and compared these data with available whole exome sequencing data from 415 men used as population controls. Moreover, we genotyped the two most frequent FANCM mutations (c.5101C>T and c.5791C>T) in 506 …
Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype
Background: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. Patients and methods: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for prima…
Additional file 1: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Male BRCA1 and BRCA2 mutation carriers by study group/country. (DOCX 21 kb)
Additional file 4: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Pathology of BRCA1 and BRCA2 MBCs and ORs in predicting BRCA2 mutation carrier status. (DOCX 20 kb)
Additional file 3: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Methods and thresholds used to define the final marker variables for study groups providing MBC cases. (DOCX 20 kb)
Prognostic significance of p16INK4a alterations and 9p21 loss of heterozigosity in locally advanced laryngeal squamous cell carcinoma
The p16INK4a gene, localized within chromosome 9p21, has been identified as a cyclin-dependent kinase inhibitor and may negatively regulate the cell cycle acting as a tumor suppressor. Genetic alterations involving the 9p21 region are common in human cancers. A consecutive series of 64 untreated patients (median of follow up 53 months) undergoing surgical resection for locally advanced laryngeal squamous-cell carcinomas (LSCCs) has been studied prospectively. Our purpose was to investigate p16 alterations (9p21 allelic loss, hypermethylation and point mutations) and their possible association with clinico-pathological data and flow cytometric variables (DNA-ploidy and S-phase fraction (SPF)…
Hereditary common cancers: molecular and clinical genetics.
This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family …
DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.
Purpose: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. Methods: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. Results: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P < 0.05) and DNA aneuploid tumors (P < …
Insight into genetic susceptibility to male breast cancer by multigene panel testing: results from a multicenter study in Italy
Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 n…
Additional file 2: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
List of local ethics committees that granted approval for the access and use of the data in present study. (DOCX 23 kb)
Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy
Recently, the number of studies on male breast cancer (MBC) has been increasing. However, as MBC is a rare disease there are difficulties to undertake studies to identify specific MBC subgroups. At present, it is still largely unknown whether BRCA-related breast cancer (BC) in men may display specific characteristics as it is for BRCA-related BC in women. To investigate the clinical–pathologic features of MBC in association with BRCA mutations we established a collaborative Italian Multicenter Study on MBC with the aim to recruit a large series of MBCs. A total of 382 MBCs, including 50 BRCA carriers, were collected from ten Italian Investigation Centres covering the whole country. In MBC p…
Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy
It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common low-penetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 age-matched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43–2.05;…
Additional file 6: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Pathology of invasive MBCs in the general population from SEER and BRCA1 MBCs and ORs in predicting male BRCA1 mutation carrier status. (DOCX 19 kb)
Additional file 3: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Methods and thresholds used to define the final marker variables for study groups providing MBC cases. (DOCX 20 kb)
DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as independent predictors of clinical outcome in operable gastric carcinoma: Results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study
BACKGROUND The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were fol…
BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases
Male breast cancer (MBC) is a rare and poorly known disease. Germ-line mutations of BRCA2 and, to lesser extent, BRCA1 genes are the highest risk factors associated with MBC. Interestingly, BRCA2 germ-line rearrangements have been described in high-risk breast/ovarian cancer families which included at least one MBC case. Germ-line mutations of CHEK2 gene have been also implicated in inherited MBC predisposition. The CHEK2 1100delC mutation has been shown to increase the risk of breast cancer in men lacking BRCA1/BRCA2 mutations. Intriguingly, two other CHEK2 mutations (IVS2+1G>A and I157T) and a CHEK2 large genomic deletion (del9-10) have been associated with an elevated risk for prostate c…
Additional file 2: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
List of local ethics committees that granted approval for the access and use of the data in present study. (DOCX 23 kb)
Additional file 1: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Male BRCA1 and BRCA2 mutation carriers by study group/country. (DOCX 21 kb)
Additional file 4: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Pathology of BRCA1 and BRCA2 MBCs and ORs in predicting BRCA2 mutation carrier status. (DOCX 20 kb)
Evaluation of CYP17A1 and CYP1B1 polymorphisms in male breast cancer risk
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 brea…
Additional file 5: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Pathology of invasive BRCA1 female and male breast tumours and ORs in predicting male BRCA1 mutation carrier status. (DOCX 19 kb)
Association of SULT1A1 Arg213His polymorphism with male breast cancer risk: results from a multicenter study in Italy
Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg213His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg213His could exert an effect on MBC developme…
Whole-exome sequencing and targeted gene sequencing provide insights into the role ofPALB2as a male breast cancer susceptibility gene
BACKGROUND Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutation–negative MBC cases. METHODS Germ-line DNA of 1 male and 2 female BRCA1/2 mutation–negative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results w…
Additional file 6: of Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Pathology of invasive MBCs in the general population from SEER and BRCA1 MBCs and ORs in predicting male BRCA1 mutation carrier status. (DOCX 19 kb)
Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy
Increasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and within BC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subj…
Havep53gene mutations and protein expression a different biological significance in colorectal cancer?*
p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein overexpression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 protei…
SULT1A1 gene deletion in BRCA2-associated male breast cancer: a link between genes and environmental exposures?
SULT1A1, a member of sulfotransferase superfamily, is a drug and hormone metabolizing enzyme involved in the metabolism of a variety of potential mammary carcinogens of endogenous and exogenous origin. Interestingly, the metabolic activity of SULT1A1 can be affected by varia- tions in gene copy number. Male Breast Cancer (MBC) is a rare disease and less investigated disease compared to female BC (FBC). As in FBC, the concurrent effects of genetic risk factors, particularly BRCA2 mutations, increased exposure to estrogens and environmental carcinogens play a relevant role in MBC. By quantitative real-time PCR with TaqMan probes, we investigated the presence of SULT1A1 gene copy number variat…