scholarly journals Hereditary Pancreatic Cancer: A Retrospective Single-Center Study of 5143 Italian Families with History of BRCA-Related Malignancies

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 193 ◽  
Author(s):  
Angela Toss ◽  
Marta Venturelli ◽  
Eleonora Molinaro ◽  
Stefania Pipitone ◽  
Elena Barbieri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pancreatic Cancer ◽  
Family History ◽  
Future Research ◽  
Brca Testing ◽  
Brca Mutations ◽  
Cancer History ◽  
Pathogenic Variants ◽  
Cancer Cluster ◽  
History Of

The identification of BRCA mutations plays a crucial role in the management of hereditary cancer prevention and treatment. Nonetheless, BRCA-testing in pancreatic cancer (PC) patients is not universally introduced in clinical practice. A retrospective analysis was conducted, firstly, to evaluate the rate of BRCA-positive families among those presenting a family history of PC besides breast and/or ovarian cancer. Secondly, the relationship between BRCA pathogenic variants and PC risk was evaluated. Finally, the characteristics of PC developed in BRCA families were described. Among 5143 family trees reporting breast and/or ovarian cancer cases, 392 showed a family history of PC. A total of 35 families (24.5% selected by the Modena Criteria and 21.3% by the NCCN Criteria) were positive to BRCA testing. Among the BRCA1 mutations, 36.8% were found within a region defined by c.3239–c.3917, whilst 43.7% of BRCA2 mutations were located within c.7180–c.8248. This study confirmed that an increase in the rate of positive tests in families with PC when associated to breast and/or ovarian tumors. Moreover, this analysis indicated two possible Pancreatic Cancer Cluster Regions that should be verified in future research. Finally, PC in families with breast and/or ovarian cancer history, particularly in BRCA families, were diagnosed at younger age and showed better one-year overall survival.

Preventing Future Cancers by Testing Women With Ovarian Cancer for BRCA Mutations

2010 ◽  
Vol 28 (4) ◽  
pp. 675-682 ◽  
Author(s):  
Janice S. Kwon ◽  
Molly S. Daniels ◽  
Charlotte C. Sun ◽  
Karen H. Lu
Keyword(s):  
Ovarian Cancer ◽  
Cost Effectiveness ◽  
Family History ◽  
Brca Mutation ◽  
Health Benefit ◽  
Ashkenazi Jewish ◽  
Brca Testing ◽  
Brca Mutations ◽  
Jewish Ancestry ◽  
History Of

Purpose Women with ovarian cancer have a 10% probability of carrying a BRCA mutation. If a mutation is identified, unaffected family members can undergo genetic testing and cancer risk-reducing strategies. We estimated the net health benefits and cost-effectiveness of different criteria for BRCA mutation testing in women with ovarian cancer, and the downstream benefits for their first-degree relatives (FDRs). Methods We developed a Markov Monte Carlo simulation model to compare four criteria for BRCA testing in women with ovarian cancer: no testing (reference); only if personal history of breast cancer, family history of breast/ovarian cancer, or Ashkenazi Jewish ancestry; only if invasive serous cancer; any invasive nonmucinous epithelial cancer. Net health benefit was life expectancy for FDRs and primary outcome was the incremental cost-effectiveness ratio (ICER). The model estimated the number of future breast and ovarian cancer cases in FDRs. Results BRCA testing based on personal/family history and ancestry could prevent future cases in FDRs with an ICER of $32,018 per year of life (LY) gained compared with the reference strategy. BRCA testing based on serous or any nonmucinous epithelial ovarian cancer could prevent more cancer cases, but at ICERs of $128,465 and $148,363 per LY gained, respectively. Conclusion BRCA testing of women with ovarian cancer based on personal/family history of cancer or Ashkenazi Jewish ancestry is a cost-effective strategy to prevent future breast and ovarian cancers among FDRs. More inclusive testing strategies prevent additional cancer cases but at significant cost.

BRCA mutations and their clinical relevance in unselected pancreatic cancer population.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16240-e16240
Author(s):  
Viola Barucca ◽  
Andrea Petricca Mancuso ◽  
Salvatore De Marco ◽  
Daniela Iacono ◽  
Carmelilia De Bernardo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Disease Progression ◽  
Personal History ◽  
First Line ◽  
Brca Mutations ◽  
Cancer Family ◽  
Cancer Family History ◽  
Brca 2 ◽  
History Of

e16240 Background: Germline pathogenetic mutations in BRCA1/2 genes are described in pancreatic cancer patients (PCP) in about 5–9% of cases. The purpose of this study was to determine their relevance in an unselected consecutive cohort of PCP describing family and clinical history. Methods: Patients (pts) were recruited at a single cancer center from September 2019 to October 2020. Participants provided blood for DNA analysis; cancer family history and treatment records were reviewed; DNA was analyzed by Next Generation Sequencing and multiplex ligation-dependent probe amplification for germline variants in BRCA1/2 Results: 69 pts were included, 61 (88,4%) with locally advanced and metastatic pancreatic cancer received first line chemotherapy and 38 (62%) were full eligible for BRCA analysis; 8 out of 69 pts were BRCA screened even if in adjuvant setting, 10 patients are still under evaluation. Out of the 38 first line screened PCP germline BRCA mutations were found in 9 (19%): 4 pts (8,7%) with pathogenetic BRCA-2 variants (subgroup 1 – S1) and 5 pts (10,8%) with variants of unknown significances (VUSs), i.e. c.5339T>C and c.5096G>A in BRCA1 (subgroup 2 – S2). Samples from 29 pts were established as BRCA wild-type (subgroup 3 – S3). Pathogenetic BRCA-2 variants were observed in 2 male and 2 female (median age, 61.5 years, range 48-69), 3 out 4 without family history of breast, ovarian and pancreatic cancer, one patient (pt) had ovarian cancer family history. All pts had a negative personal history of others cancers. All S1 pts received FOLFIRINOX regimen achieving one complete response, 2 partials responses and 1 disease progression with RECIST criteria. The S2 included 2 male and 3 female (median age, 61 years, range 45-70) 2 with family history of pancreatic cancer, no pt had personal history of others cancers; 2 pts had stable disease and 3 disease progression receiving platinum-based regimen (4 pts) and gemcitabine/nabpaclitaxel (1 pt), respectively. Platinum responders were observed only in the well known pathogenetic BRCA-2 variants group with twice a median progression-free survival (PFS, months -ms-) as compared to the one observed in VUSs group. (>6 C.I. 95% 2- >12 ms; vs 3 ms, 95% C.I. 3-12 ms). S3 included 9 male and 20 female, (median age, 66 years, range 42-78); 5 pts had family history of pancreatic or breast cancer, 5 pts had a personal history of other cancers (breast and thyroid). In this group,16 pts received a platinum based regimen and 12 pts have been treated without platinum based regimen. Conclusions: Our results suggest that: 1) BRCA pathogenetic mutations rate (8,7%) is in line with literature data and seems not to be related with family or personal history, and to be associated with a better outcome; 2) No BRCA mutations were detected in patients over 70 years. 3) VUSs subgroup do not seem to benefit from platinum-regimen.

scholarly journals Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kodai Abe ◽  
Arisa Ueki ◽  
Yusaku Urakawa ◽  
Minoru Kitago ◽  
Tomoko Yoshihama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Genetic Analysis ◽  
Pathogenic Variant ◽  
Familial Pancreatic Cancer ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Pancreatic Cancers ◽  
Epidemiological Surveys ◽  
History Of

Abstract Background Family history is one of the risk factors for pancreatic cancer. It is suggested that patients with pancreatic cancer who have a familial history harbor germline pathogenic variants of BRCA1 and/or BRCA2 (BRCA1/2), PALB2, or ATM. Recently, some germline variants of familial pancreatic cancers (FPCs), including PALB2, have been detected. Several countries, including Japan, perform screening workups and genetic analysis for pancreatic cancers. We have been carrying out active surveillance for FPC through epidemiological surveys, imaging analyses, and genetic analysis. Case presentation Here, we present the case of a female patient harboring pathogenic variants of PALB2 and NBN, with a family history of multiple pancreatic cancer in her younger brother, her aunt, and her father. Moreover, her father harbored a PALB2 pathogenic variant and her daughter harbored the same NBN pathogenic variant. Given the PALB2 and NBN variants, we designed surveillance strategies for the pancreas, breast, and ovary. Conclusions Further studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression.

Germline mutations in Brazilian pancreatic carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16749-e16749
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Luiz A.Senna Leite ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Carcinoma ◽  
Germline Mutations ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
History Of ◽  
History Of Cancer

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

scholarly journals The genetic analysis of a founder Northern American population of European descent identifies FANCI as a candidate familial ovarian cancer risk gene

2020 ◽  
Author(s):  
Caitlin T Fierheller ◽  
Laure Guitton-Sert ◽  
Wejdan M Alenezi ◽  
Timothée Revil ◽  
Kathleen K Oros ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Family History ◽  
Serous Carcinoma ◽  
Ovarian Cancer Risk ◽  
Repair Pathway ◽  
Degree Relative ◽  
Pathogenic Variants ◽  
Familial Ovarian Cancer ◽  
History Of

AbstractSome familial ovarian cancer (OC) could be due to rare risk alleles in genes that each account for a relatively small proportion of cases not due to BRCA1 and BRCA2, major risk genes in the homologous recombination (HR) DNA repair pathway. We report a new candidate OC risk allele, FANCI c.1813C>T in a Fanconi anemia (FA) gene that plays a role upstream of the HR DNA repair pathway. This variant was identified by whole exome sequencing of a BRCA1 and BRCA2 mutation-negative French Canadian (FC) OC family from a population exhibiting founder effects. In FCs, the c.1813C>T allele was detected in 7% (3/43) of familial and 1.6% (7/439) of sporadic OC cases; and in 3.7% (3/82) of familial breast cancer (BC) cases with a family history of OC and in 1.9% (3/158) of BC only families. This allele was significantly associated with FC BRCA1 and BRCA2 mutation-negative OC families (OR=5.6; 95%CI=1.6-19; p=0.006). Although FANCI c.1813C>T was detected in 2.5% (74/2950) of cancer-free FC females, carriers had a personal history of known OC risk reducing factors, and female/male carriers were more likely to have reported a first-degree relative with OC (ρ=0.037; p=0.011). Eight rare potentially pathogenic FANCI variants were identified in 3.3% (17/516) of Australian OC cases, including 10 carriers of FANCI c.1813C>T. Potentially pathogenic FANCI variants were significantly more common in AUS OC cases with a family history of OC than in isolated OC cases (p=0.027). The odds ratios (OR) were >3 for carriers of any of the seven rarest FANCI alleles, and 1.5 for c.1813C>T. Data from the OC Association Consortium revealed that the ORs for the c.1813C>T allele were highest for the most common OC subtypes. Localization of FANCD2, part of the FANCI-FANCD2 (ID2) binding complex in the FA pathway, to sites of induced DNA damage was severely impeded in cells expressing the p.L605F isoform. This isoform was expressed at a reduced level; unstable by formaldehyde or mitomycin C treatment; and exhibited sensitivity to cisplatin but not to olaparib (a poly [ADP-ribose] polymerase inhibitor). By tissue microarray analyses, FANCI protein was robustly expressed in fallopian tube epithelial cells but expressed at low-to-moderate levels in 88% (83/94) of high-grade serous carcinoma OC samples. This is the first study to describe potentially pathogenic variants in OC in a member of the ID2 complex of the FA DNA repair pathway. Our data suggest that potentially pathogenic FANCI variants may modify OC risk in cancer families.

scholarly journals Incidence of Pathogenic Variants in Those With a Family History of Pancreatic Cancer

2018 ◽  
Vol 8 ◽  
Author(s):  
Sarah K. Macklin ◽  
Pashtoon M. Kasi ◽  
Jessica L. Jackson ◽  
Stephanie L. Hines
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pathogenic Variants ◽  
History Of

Incidence of pathogenic variants in individuals with a personal or family history of pancreatic cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 1589-1589
Author(s):  
Pashtoon Murtaza Kasi ◽  
Sarah K Macklin ◽  
Stephanie L. Hines
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pathogenic Variants ◽  
History Of

Family history and pathogenic/likely pathogenic germline variants in prostate cancer patients.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 143-143
Author(s):  
Rachel Sabol ◽  
Elisa Marie Ledet ◽  
Ellen Jaeger ◽  
Marcus W. Moses ◽  
Brian E. Lewis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Personal History ◽  
Sample Collection ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
Damage Repair ◽  
History Of

143 Background: Recent literature highlights the importance of germline genetic testing in prostate cancer (PCa) patients. Surprisingly, a literature review indicates that family history records are incomplete in published studies. Methods: Prospective and complete family history data were gathered from 496 men in a single institution with a personal history of PCa who underwent germline genetic testing using a panel of at least 79 genes (Invitae testing) from 2016-2020. Comprehensive FH were obtained in all PCa patients in this database and analysis of prevalent FH was assessed at the time of sample collection. Age, race, metastastes at any time, and Gleason score were also ascertained. MUTYH heterozygotes were not considered pathogenic. Results: Pathogenic/likely pathogenic variants (PV/LPVs) were not associated with age at diagnosis, race, or presence of metastasis. Men with Gleason scores 8-10 at time of diagnosis were more likely to have PV/LPV ( P= 0.004). One or more first degree relatives (FDR) with any cancer with was not predictive for germline PV/LPVs for men with PCa ( P= 0.96). Analysis of patients with one or more FDR with breast, prostate, ovarian, or pancreatic cancer revealed that only FDR with breast cancer ( P = 0.028) or ovarian cancer ( P = 0.015) was predictive for PV/LPVs. Though one or more FDR with prostate cancer did not predict a PV/LPV in the overall panel, further analysis indicate that a history of a FDR with PCa was predictive for PV/LPV in a DNA damage repair (DDR) gene ( P= 0.044). Conclusions: In men with a personal history of PCa, germline PV/LPVs were associated with a FDR with breast or ovarian cancer. A FDR with PCa was predictive for PV/LPV in DDR genes. These data emphasize the contribution of FH to germline genetic testing results in a cohort with complete ascertainment of cancer in first degree relatives.

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