The clinical and molecular characteristics of patients with personal or family history of gastrointestinal malignancies/polyposis and checkpoint kinase 2 (CHEK2) mutations.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 44-44
Author(s):  
Sana Ozair ◽  
Cassandra Gurganus ◽  
Veena Krishnan ◽  
Gideon T Dosunmu ◽  
Delmer Alfredo Montoya Motino ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Family History ◽  
Personal History ◽  
Molecular Characteristics ◽  
Gastrointestinal Malignancies ◽  
Checkpoint Kinase ◽  
Chek2 Gene ◽  
Chek2 Mutation ◽  
Checkpoint Kinase 2 ◽  
History Of

44 Background: Checkpoint Kinase 2 (CHEK 2) encodes the protein CHK2, a serine/threonine kinase involved in pathways that conduct DNA repair as well as apoptosis in response to initial DNA damage. Germline mutations in the CHEK2 gene are associated with several malignancies such as colon, breast, stomach, prostate, kidney, thyroid and soft tissue cancers. Here, we describe the clinical and molecular characteristics of patients with personal or family history of gastrointestinal (GI) malignancies/polyposis and CHEK2 gene mutations. Methods: This is an IRB-approved retrospective chart-review study. Between 2016 and 2020, 1011 unique genetic counseling visits were conducted. Germline testing was recommended by a certified genetic counselor if medically necessary. All patients with a germline CHEK2 mutation were identified (N = 16). Patients with a CHEK2 mutation and personal and family history of GI malignancies/polyposis were further explored and their clinical and molecualr characteristics are summarized. Results: The reasons for referral to the Cancer Genetics Counseling Services in patients with pathogenic CHEK2 mutations were personal history of colon cancer (N = 3) and family history of colon cancer (N = 4). One patient with the CHEK2 c.1100delC mutation had a personal history of juvenile polyposis syndrome and a family history of colon cancer. In our cohort, 11 out of 16 (69%) patients had a CHEK2 mutation and personal or family history of GI malignancies/polyposis. The median age was 57 years old (25-80). Six (55%) patients were males. All (100%) patients were Caucasians. Seven (64%) patients had a pathogenic germline CHEK2 mutation and 4 (36%) patients had a variant of unknown significance (VUS). Among patients with pathogenic germline CHEK2 mutations (N = 7), 5 (72%) patients had CHEK2 c.1100delC mutation, 1 (14%) patient had CHEK2 c.190G > A mutation and 1 (14%) patient had CHEK2 c.470T > C mutation. The CHEK2 VUS mutations seen in our cohort were CHEK2 c.539G > A, CHEK2 p.V395L, CHEK2 gain of exons 3-15 and CHEK2 c.1421G > A mutations. Conclusions: All patients in our cohort with CHEK2 mutations were Caucasians. The majority of our patients (69%) had an underlying personal or family history of GI malignancies/polyposis. In patients with personal or family history of GI malignancies/polyposis and CHEK2 mutation, 64% were found to have pathogenic CHEK2 mutations. The most common diagnosed CHEK2 mutation in our cohort was CHEK2 c.1100delC mutation.

scholarly journals Homozygous Germline APC p.I1307K Variants: A Case Series

2021 ◽  
pp. 1295-1303
Author(s):  
Alexa Rosenblum ◽  
Michelle Springer ◽  
Amanda Eppolito ◽  
Lisen Axell ◽  
Lisa Mohler
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Family History ◽  
Cancer Genetics ◽  
Phenotypic Variability ◽  
Case Series ◽  
Personal History ◽  
Ashkenazi Jewish ◽  
Screening And Surveillance ◽  
History Of

Approximately 10% of all colorectal cancer is estimated to be due to an inherited predisposition. Identification of a germline pathogenic variant can aid in treatment, screening, and surveillance and help stratify familial cancer risks based on gene-specific cancer associations. The <i>APC</i> gene contributes to a small percentage of hereditary colon cancer, with most pathogenic <i>APC</i> variants causing familial adenomatous polyposis syndrome. However, one specific variant in <i>APC</i> called p.I1307K, found in approximately 10% of Ashkenazi Jewish individuals, is associated with a moderate risk for colon cancer, but not polyposis. Heterozygous carriers of one p.I1307K variant are well documented in the literature, and guidelines recommend earlier and more frequent colonoscopies. Conversely, reports of homozygous carriers of 2 p.I1307K variants are limited, and guidelines for medical management are lacking. This case series describes 4 homozygous p.I1307K patients of Ashkenazi Jewish ancestry identified in cancer genetics clinics. Case 1 is a 73-year-old pancreatic cancer patient with a family history of melanoma and colon cancer. Case 2 is a 62-year-old patient with a personal history of 4 adenomatous colorectal polyps and a family history of breast, pancreatic, colon, and prostate cancers. Case 3 is a 52-year-old patient with a personal history of early-onset breast cancer and uveal melanoma and a family history of breast, prostate, and stomach cancers. Case 4 is a 70-year-old patient with a personal history of gallbladder adenocarcinoma and a family history of breast cancer. These cases exhibit wide phenotypic variability and contribute to the limited reports of homozygous p.I1307K variant carriers.

scholarly journals Clinical, Pathological and Molecular Characteristics of Chilean Patients with Early-, Intermediate- and Late-Onset Colorectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 631
Author(s):  
Karin Alvarez ◽  
Alessandra Cassana ◽  
Marjorie De La Fuente ◽  
Tamara Canales ◽  
Mario Abedrapo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Age Of Onset ◽  
Late Onset ◽  
Molecular Characteristics ◽  
Family History Of Cancer ◽  
Molecular Features ◽  
Age Of Diagnosis ◽  
History Of ◽  
History Of Cancer

Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51–69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan–Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.

The Neuropathic Diathesis, or the Diathesis of the Degenerate

1888 ◽  
Vol 34 (146) ◽  
pp. 167-176
Author(s):  
G. T. Revington
Keyword(s):  
Family History ◽  
Normal Development ◽  
Personal History ◽  
Striking Feature ◽  
General Paralysis ◽  
History Of ◽  
The Creation ◽  
The Individual ◽  
The Mind

I think that the foregoing statistics, and those which follow, together with the large number of cases which I quote, and which connect general paralysis with almost every form of neurotic manifestation, will prove conclusively that neurotic inheritance is a striking feature in the causation of general paralysis. I question whether a distinction between “the cerebral and the insane element” in general paralysis can be maintained. If general paralysis is not a degeneration of the mind-tissue, then the pathology of insanity has no existence, and I would say that the subtle influence for evil, which is transmitted from parents, whose brains are deteriorated by neurotic outbursts, or soaked in alcohol, or wrecked by physiological immorality, tends strongly towards such degeneration. If insanity is, as Dr. Savage says, a perversion of the ego, then a general paralytic is the in-sanest of the insane. We know that the children of a melancholic parent, for example, may develop any form of neurosis—in other words, it is not that melancholia or general paralysis, or any other definite disease, is transmitted, but that a certain tendency to deviate from normal development is transmitted. This tendency to deviate is the neurotic diathesis, and the form of its development is determined by collateral circumstances, and a certain series of collateral circumstances determine the development of general paralysis. Perhaps neurotic inheritance may mean in some cases a limited capital of nervous energy, and if this is wasted recklessly the individual breaks down suddenly and pathologically, as we all do slowly and physiologically. I would also point out that considering the number of histories of insanity which owing to ignorance or reticence we, do not receive, and considering that we never receive information as to the existence of the slighter neuroses, it is marvellous that we get so high a percentage as 51. Of the 145 general paralytics with a reliable history, 38 had a family history of insanity, 28 a family history of drink, 8 of both, 43 had a personal history of drink, 8 of a previous attack too remote to be considered, at least, according to our present ideas, as part of the disease, and the vast majority had a history of some physiological irregularity which must be considered as conducive to the creation of an acquired neurosis. We may now pass to some further statistics.

A Practical Approach to Pediatric Patients Referred With an Abnormal Coagulation Profile

2005 ◽  
Vol 129 (8) ◽  
pp. 1011-1016 ◽  
Author(s):  
Monica Acosta ◽  
Rachel Edwards ◽  
E. Ian Jaffe ◽  
Donald L. Yee ◽  
Donald H. Mahoney ◽  
...  
Keyword(s):  
Family History ◽  
Positive Family History ◽  
Laboratory Data ◽  
Bleeding Risk ◽  
Personal History ◽  
Retrospective Case ◽  
Laboratory Assessment ◽  
Repeat Testing ◽  
Effective Manner ◽  
History Of

Abstract Context.—Workup for prolonged prothrombin time (PT) and activated partial thromboplastin time (PTT) is a frequent referral to a Hematology and Coagulation Laboratory. Although the workup should be performed in a timely and cost-effective manner, the complete laboratory assessment of the coagulation state has not been standardized. Objective.—To determine which clinical and laboratory data are most predictive of a coagulopathy and to formulate the most efficient strategy to reach a diagnosis in patients referred for abnormal coagulation profiles. Design.—Retrospective case review. Medical records of 251 patients referred for prolonged PT and/or PTT to our Hematology Service between June 1995 and December 2002 were reviewed. Results.—The study included 135 males and 116 females with a mean age of 7.0 years. A personal history of bleeding was reported in 137 patients, and a family history of bleeding was reported in 116 patients. Fifty-one patients (20%) had a coagulopathy (ie, a bleeding risk). Factors predictive of a bleeding risk were a positive family history of bleeding (P &lt; .001) and a positive personal history of bleeding (P = .001). Of 170 patients with findings of normal PT and PTT values on repeat testing, 14 were subsequently diagnosed with a coagulopathy. Two of these patients reported no positive personal or family history of bleeding. Conclusions.—Coagulopathy was identified in 20% of the children referred for abnormal PT and/or PTT. In the absence of a personal or family history of bleeding, a normal PT and/or PTT on repeat testing has a negative predictive value of more than 95%.

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.

Is Migraine Associated with Right-to-Left Shunt a Separate Disease? Results of the SAM Study

Cephalalgia ◽  
2008 ◽  
Vol 28 (4) ◽  
pp. 360-366 ◽  
Author(s):  
GP Anzola ◽  
G Meneghetti ◽  
C Zanferrari ◽  
A Adami ◽  
L Dinia ◽  
...  
Keyword(s):  
Family History ◽  
Observational Study ◽  
Transcranial Doppler ◽  
Patent Foramen Ovale ◽  
Genetic Linkage ◽  
Personal History ◽  
Coagulation Disorders ◽  
Foramen Ovale ◽  
History Of ◽  
Pfo Closure

Migraine with aura (MA) is associated with the persistence of patent foramen ovale (PFO) in about 50% of cases, and migraineurs tend to have larger shunts than controls, suggesting that right-to-left shunt (RILES) determined by PFO could play a role in triggering migraine attacks. Moreover, some preliminary reports have suggested that PFO closure may give relief to both migraine and aura attacks. The aim of this study was to clarify if shunt-associated migraine (SAM) has clinical features that allow a distinction from shunt-unrelated migraine (SUM), in a prospective, multicentre, observational study (SAM study). We enrolled consecutive MA patients, who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. All were systematically screened for RILES with transcranial Doppler, and for coagulation disorders. Overall, 460 patients were included; the SUM and SAM classes comprised 58% and 42% of patients, respectively. SAM patients were significantly younger (34.1 ± 10 vs. 37.1 ± 11 years), had a more frequent family history of migraine (76% vs. 66%) and a higher frequency of sensory symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of SAM with other cardiac abnormalities and with coagulation disorders. The SAM study suggests that the effect of RILES on migraine features is not relevant. The higher family history of migraine in SAM suggests a possible genetic linkage between migraine and RILES.

Does a family history of adenomatous colon polyp(s) in a first-degree relative pose an increased risk of developing colon cancer?

2018 ◽  
Vol 21 (4) ◽  
pp. E8
Author(s):  
Ernestine Clements ◽  
Lena Gamble ◽  
Nathan Way ◽  
Lacy Smith ◽  
John B. Waits
Keyword(s):  
Colon Cancer ◽  
Family History ◽  
Colon Polyp ◽  
Degree Relative ◽  
Increased Risk ◽  
History Of ◽  
Relative Pose

scholarly journals Family history of cancer, personal history of medical conditions and risk of oral cavity cancer in France: the ICARE study

BMC Cancer ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Loredana Radoï ◽  
Sophie Paget-Bailly ◽  
Florence Guida ◽  
Diane Cyr ◽  
Gwenn Menvielle ◽  
...  
Keyword(s):  
Family History ◽  
Oral Cavity ◽  
Oral Cavity Cancer ◽  
Personal History ◽  
Medical Conditions ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

Clinical and Economic Impact of Pre-Operative Coagulation Screening in Children

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3379-3379
Author(s):  
Trishala Agrawal ◽  
Louisa Mazza-Hilway ◽  
Alice J. Cohen ◽  
Sari H Jacoby
Keyword(s):  
Family History ◽  
Major Bleeding ◽  
Conflicts Of Interest ◽  
Personal History ◽  
Screening Tests ◽  
Factor Vii ◽  
Factor Xii ◽  
Coagulation Tests ◽  
History Of ◽  
The Mean

Abstract Abstract 3379 Background: The literature in the past has recommended pre-operative (PRE-O) coagulation screening only when indicated by history or physical exam. Despite these recommendations, surgeons continue to order PT and PTT prior to surgery, especially in children, because they have often not been hemostatically challenged. We evaluated the usefulness of screening tests in identifying significant bleeding risk and associated cost. Methods: We performed a retrospective audit on children referred to the hemophilia center sent for further evaluation of abnormal PT and PTT on PRE-O screening. We reviewed 62 patients who had 80 procedures, out of which 70 procedures were evaluable with complete data. Age, personal and family history of bleeding, coagulation tests, PRE-O and post-operative (PO) treatment, and immediate PO bleeding were assessed. Results: The most common procedure that led to PRE-O screening was tonsillectomy/adenoidectomy at 61% (49/80). Other procedures included orthopedic, GI, oral, dental extractions, and myringotomies. Only 2.5% (2/80) were cardiac procedures. The mean patient age was 6 years (range 1–16). 55% (34/62) had no personal or family history of bleeding. 22.5% (14/62) had a family history of mild bleeding such as epistaxis or menorrhagia. 8% (5/62) had a family history of major bleeding disorders such as Von Willebrand disease (VWD) or hemophilia. 14.5% (9/62) had a personal history of bleeding, mild or major. The most common abnormal screening test was the PT at 40% (25/62). 27% (17/62) had an abnormal PTT (3.2% \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(262\) \end{document} with a significantly abnormal PTT above 50). 22.5% (14/62) were referred for abnormal PT/PTT. 8% (5/62) with an abnormal PT and/or PTT corrected on repeat studies. The remaining 9.6% (6/62) were referred for other reasons such as positive family or personal history and a high risk procedure. Additional coagulation tests ordered because of prolonged PT or PTT varied and included additional factor assays (Table 1). The mean cost of additional testing was >$1000. Factor VII was the most common factor deficiency identified with a mean activity of 47% (27–54%) (normal 55–163%) followed by factor XII deficiency with a mean activity of 39% ( 19–49%) (normal 46–168%). PRE-O, 5 patients received support with either Humate P, Stimate, Amicar, or DDAVP, 4 with a diagnosis of VWD and 1 with Jacobsen Syndrome; 3 of these patients received PO Amicar. PO, 69/70 procedures were completed with minimal (2–45 mL) bleeding. Only 1/70 procedures had significant PO bleeding, despite normal tests. This patient did not have any significant immediate PO bleeding, but had delayed bleeding reported at day 7 requiring cauterization. No other cases of delayed PO bleeding were reported to our clinic. Conclusion: In patients who undergo routine screening by laboratory testing only, the most common abnormality found was a prolonged PT. Subsequent workup of patients with abnormal screening tests identified factor VII or factor XII deficiencies most frequently. Only one patient with abnormal PT/PTT was diagnosed with a significant bleeding disorder, VWD. Major bleeding occurred rarely. This study demonstrates that the cost of extensive PRE-O coagulation testing is high with minimal clinical impact. Disclosures: No relevant conflicts of interest to declare.

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