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.

Healthcare disparities and the demand for expanding hereditary breast cancer screening guidelines in African Americans.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13636-e13636
Author(s):  
Jordan Alana Ciuro ◽  
Samira Ahsan ◽  
Alisha Beyer ◽  
Nancy Jackson
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Family History ◽  
High Risk ◽  
African Americans ◽  
Personal History ◽  
Ashkenazi Jewish ◽  
Breast And Ovarian Cancer ◽  
African American Population ◽  
History Of

e13636 Background: The role of predictive genetic testing on cancer care continues to rise in the healthcare community due to increased development, high demand and utilization of multi-panel testing and genome sequencing. BRCA1 and BRCA2 (BRCA1/2) mutations constitute some of the most common, targetable and clinically important markers in breast cancer. Individuals who harbor BRCA1/2 mutation have a substantially increased risk of developing a multitude of cancers, including breast and ovarian cancer. Early detection of these mutations leads to genetic and prevention counselling. The National Comprehensive Cancer Network (NCCN) guidelines recommend BRCA1/2 screening in high risk individuals however has not incorporated differences within ethnic cohorts. Methods: This study reviewed data collected from a genetics clinic in a tertiary community hospital from 2008 to 2018 to analyze the prevalence of BRCA1/2 mutations in various ethnicities as well as identify high risk personal characteristics and family history. A retrospective chart analysis was conducted on 1090 high risk patients seen for genetic counselling for hereditary breast and ovarian cancer syndrome. Results: Among cases, BRCA1/2 mutations were significantly more common in African American when compared to non-Ashkenazi Jewish Caucasians (8.1% vs 3.6%, p = 0.020). African Americans were more likely to have a personal history of any cancer compared to non-Ashkenazi Jewish Caucasians (90.4% vs 84.5 %, p = 0.048). African Americans were also more likely to have personal history of breast cancer compared to non-Ashkenazi Jewish Caucasians (86.4% vs 79.6%, p = 0.048). Regarding family history, there was no significant difference in the prevalence of cancer. Conclusions: In conclusion, we observed a significantly higher rate of BRCA1/2 in the African American population when compared to non-Ashkenazi Jewish Caucasians. Given the documented social barriers such as insurance and lack of knowledge of family history, the prevalence of BRCA1/2 might be underrepresented in literature. It is critical for healthcare providers to assess probability of BRCA1/2 mutations in the African American population and consequently order genetic testing when appropriate. Future studies are needed in this ethnic cohort to establish if a more tailored approach would help identify higher risk individuals.

scholarly journals Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG)

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 411-444 ◽  
Author(s):  
Kevin J Monahan ◽  
Nicola Bradshaw ◽  
Sunil Dolwani ◽  
Bianca Desouza ◽  
Malcolm G Dunlop ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Great Britain ◽  
Family History ◽  
Cancer Genetics ◽  
Genetic Diagnosis ◽  
Lifetime Risk ◽  
British Society ◽  
Screening And Surveillance ◽  
History Of ◽  
The Uk

Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual’s lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.

Family cancer patterns and variation by race and ethnicity among individuals with pathogenic variants in multi-gene cancer predisposition panels at a large urban comprehensive cancer center.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13540-e13540
Author(s):  
Sushma Tatineni ◽  
Kristen Purrington ◽  
Hadeel Assad ◽  
Nadine Abdallah ◽  
Meri Tarockoff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Race And Ethnicity ◽  
Cancer Predisposition ◽  
Comprehensive Cancer Center ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
History Of

e13540 Background: The identification of pathogenic variants and variants of unknown significance (VUS) in multi-gene cancer predisposition testing raises new questions regarding cancer risk and management. We evaluated the personal and family cancer patterns and variation by race and ethnicity, among individuals positive for pathogenic variants in non-BRCA1/ 2 cancer predisposing genes. Methods: The Karmanos Cancer Institute (KCI) Cancer Genetics database was queried from May 13, 2013 through December 31, 2018. There were 3,544 unrelated individuals evaluated for hereditary cancer predisposition of whom 1,868 had 18-gene panel testing at 6 sites across Michigan. Data was collected on personal and family cancer history including ages at diagnosis utilizing a 3-generation pedigree, self-identified race and ethnicity and results of genetic testing. We describe the prevalence of pathogenic variants by proband cancer diagnosis, family history, race, and ethnicity. Results: The race/ethnic distribution of the tested cohort included 67.5% non-Hispanic White (NHW), 24.4% African American (AA), 2.1% Arab, 1.8% Ashkenazi Jewish (AJ), 1.0% Hispanic, and 3.4% other. The distribution of cancer diagnoses included 40.6% breast, 5.5% ovarian, 4.1% colon, 3.5% endometrial, 2.0% pancreas and 39.7% unaffected. Pathogenic variants were seen in 151 (8.1%) individuals and VUS in 309 (16.5%). The five most common pathogenic variants were CHEK2 (40), MUTYH (22), ATM (20), and PALB2 (18). The most common pathogenic variants by race and ethnicity were CHEK2 (NHW), RAD51C (AA), PALB2 (Arab), CHEK2, MSH6 (AJ), and none in Hispanics. Variants associated with the four most common cancer types were breast ( CHEK2 ), ovarian ( CHEK2, MUTYH, BRIP1), colon ( ATM), and endometrial ( MSH6, PALB2). Of 40 individuals with CHEK2 variants, 92.5% were NHW, and 34 (85%), 31 (78%), 10 (25%), 1 (2.5%) had family history of breast cancer, breast cancer before age 50, ovarian, and colon cancer, respectively. Of 20 with ATM variants, 95% were NHW, 13 had family history data and 10 (76.9%), 8 (61.5%), 2 (15.4%), 1 (7.7%) had family history of breast, breast cancer before age 50, ovarian, and colon cancer, respectively. Conclusions: Pathogenic variants seen using multigene panel testing differ by race, ethnicity and personal/family history of cancer. This data will inform genetic counseling strategies in regards to cancer risk and management. Data on additional genes updated through 2019 will be presented.

Cancer Genetics Service Interest in Women with a Limited Family History of Breast Cancer

2009 ◽  
Vol 18 (4) ◽  
pp. 339-349 ◽  
Author(s):  
Tamara J. Somers ◽  
Julie C. Michael ◽  
William M. P. Klein ◽  
Andrew Baum
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Cancer Genetics ◽  
History Of

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 Referrals of women with a family history of breast cancer from primary care to cancer genetics services in South East Scotland

2003 ◽  
Vol 89 (9) ◽  
pp. 1650-1656 ◽  
Author(s):  
H Campbell ◽  
S Holloway ◽  
R Cetnarskyj ◽  
E Anderson ◽  
R Rush ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Care ◽  
Family History ◽  
Cancer Genetics ◽  
Genetics Services ◽  
History Of

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.

Family history of breast cancer and local recurrence after breast conserving therapy

1998 ◽  
Vol 34 ◽  
pp. S12
Author(s):  
C.T.M. Brekelmans ◽  
A.C. Voogd ◽  
G. Botke ◽  
A.N. van Geel ◽  
P. Rodrigus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Local Recurrence ◽  
Breast Conserving Therapy ◽  
History Of
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