scholarly journals The Hereditary Spectrum of Pancreatic Cancer: The Edmonton Experience

2004 ◽  
Vol 18 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Margaret Lilley ◽  
Dawna Gilchrist
Keyword(s):  
Pancreatic Cancer ◽  
At Risk ◽  
Family History ◽  
Hereditary Cancer ◽  
Cancer Genetics ◽  
Hereditary Cancer Syndrome ◽  
Molecular Testing ◽  
Cancer Syndrome ◽  
History Of ◽  
Cancer Syndromes

OBJECTIVE:Pancreatic cancer is known to aggregate in some families and has been associated with a wide variety of cancer syndromes. The authors describe their experience with pancreatic cancer and the range of associated cancer syndromes.METHODS:The charts of all patients seen for concern of a hereditary cancer syndrome in the Cancer Genetics Clinic at the University of Alberta between 1995 and 2002 were reviewed.RESULTS:Forty families reported a personal or family history of pancreatic cancer in the context of a possible hereditary cancer syndrome. Three additional families reported a history of pancreatitis. Twenty-four (56%) of those families were suspected of having a hereditary breast and ovarian cancer syndrome. A further seven (16%) were suspected of having hereditary nonpolyposis colon cancer. Only three (7%) were believed to be at risk for a site-specific pancreatic cancer syndrome. Another three (7%) were suspicious for hereditary pancreatitis. The remaining family histories were suggestive of Li-Fraumeni syndrome, von Hippel-Lindau syndrome or a nonspecific cancer predisposition.CONCLUSIONS:With such a wide variety of hereditary cancer syndromes associated with pancreatic cancer, an accurate assessment of the family history is essential to determine the most appropriate cancer screening for at-risk family members and to guide any molecular testing that may be offered.

scholarly journals High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer

2015 ◽  
Vol 33 (31) ◽  
pp. 3544-3549 ◽  
Author(s):  
Maureen E. Mork ◽  
Y. Nancy You ◽  
Jun Ying ◽  
Sarah A. Bannon ◽  
Patrick M. Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Counseling ◽  
Family History ◽  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Hereditary Cancer Syndromes ◽  
Cancer Syndrome ◽  
History Of ◽  
Cancer Syndromes ◽  
History Of Cancer

Purpose Established guidelines recommend evaluation for hereditary cancer syndromes in patients younger than 50 years diagnosed with colorectal cancer (CRC). This group has been well described in the literature; however, patients diagnosed as adolescents and young adults are not well represented in CRC studies. Here, we define the clinical profile, including the extent of hereditary cancer syndromes and family history of cancer, in patients diagnosed with CRC at age 35 or younger. Patients and Methods We reviewed patients who underwent genetic counseling at our institution during 5 years (2009 to 2013). Data were collected regarding demographics, clinicopathologic information, tumor and genetic testing, and family history. Patients with an identified hereditary cancer syndrome were compared with those without a syndrome. Results Of the 193 patients with evaluable data, 35% had an identifiable hereditary cancer syndrome, including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16 with familial adenomatous polyposis, two with constitutional mismatch repair deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni syndrome. Patients without a hereditary syndrome more frequently presented with metastatic disease, whereas patients with a syndrome were more likely to present at earlier stages and to have a family history of cancer. Nevertheless, a substantial proportion of the hereditary syndromes (19%) were diagnosed in individuals with no family history of the disease. Conclusion We conclude that patients diagnosed with CRC at age 35 years or younger should receive genetic counseling regardless of their family history and phenotype.

scholarly journals Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 169
Author(s):  
Matsubayashi ◽  
Kiyozumi ◽  
Ishiwatari ◽  
Uesaka ◽  
Kikuyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Early Stage ◽  
Developed Countries ◽  
Familial Pancreatic Cancer ◽  
Cancer Syndrome ◽  
Inherited Cancer ◽  
Clinicopathological Findings ◽  
History Of ◽  
Cancer Syndromes

A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz–Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%–10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.

Identifying individuals with primary central nervous system tumors at risk for hereditary cancer syndromes using the Utah Population Database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10532-10532
Author(s):  
Nicholas Shawn Whipple ◽  
Wendy Kohlmann ◽  
Samuel Cheshier ◽  
Zhe Yu ◽  
Karen Curtin ◽  
...  
Keyword(s):  
At Risk ◽  
Hereditary Cancer ◽  
Cancer Genetics ◽  
Cancer Surveillance ◽  
Cns Tumors ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Population Database ◽  
Cns Tumor ◽  
The Impact

10532 Background: CNS tumors are the most common solid tumors and the deadliest cancers in children. Approximately 10% of children with a CNS tumor harbor a hereditary cancer syndrome (HCS), but many will not be tested for a HCS. The Utah Population Database (UPDB) contains comprehensive cancer registry data for Utah families and can determine multigenerational cancer pedigrees across an archive of 5.8 million individuals. Early identification of HCSs results in improved cancer surveillance and outcomes, reducing the impact of CNS tumors in children. We hypothesize that the UPDB can identify children and families with HCSs not previously identified. Methods: We queried the UPDB for individuals ages 0-39 diagnosed with a primary CNS tumor (malignant and benign) between 1966-2017 and generated cancer pedigrees of 3 generations or more for probands, extending to at least third-degree relatives. Specialized software calculated a familial standardized incidence ratio (FSIR) to determine families with excess clustering of CNS tumors. Clinical cancer genetics experts reviewed pedigrees to confirm patterns of HCS. Results: We identified 4,634 CNS tumors in 4,550 individuals, of whom 2,233 (49%) reside in high-quality pedigrees containing ≥2 grandparents, at least 1 from both maternal and paternal sides. To identify families with excess clustering of CNS tumors, we selected pedigrees with an FSIR P< 0.05 and ≥2 affected patients, resulting in 161 high-risk families with a mean of 170 (median 96) relatives per pedigree of 3-6 generations. Among these 161 families, there were 2,017 unique relatives (first-third degree) of CNS probands with 2,355 tumors (any site), for a per pedigree average of 14.7 tumors in 12.5 relatives. Review of the 10 highest risk pedigrees indicated that 4 meet HCS criteria, including Li-Fraumeni (n = 2), von Hippel-Lindau (n = 1), and rhabdoid tumor predisposition (n = 1). Conclusions: The UPDB can produce multigenerational cancer pedigrees that identify individuals and families at risk of harboring a HCS who warrant germline testing. These findings should encourage clinicians to perform thorough family history screening and to always consider workup for associated HCSs.

scholarly journals RARE-24. IDENTIFYING INDIVIDUALS WITH PRIMARY CENTRAL NERVOUS SYSTEM TUMORS AT RISK FOR HEREDITARY CANCER SYNDROMES USING THE UTAH POPULATION DATABASE

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i45-i46
Author(s):  
Nicholas Whipple ◽  
Wendy Kohlmann ◽  
Samuel Cheshier ◽  
Zhe Yu ◽  
Karen Curtin ◽  
...  
Keyword(s):  
At Risk ◽  
Hereditary Cancer ◽  
Cancer Genetics ◽  
Cns Tumors ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Population Database ◽  
Cns Tumor ◽  
Von Hippel Lindau ◽  
Cancer Registry Data

Abstract Background CNS tumors are the most common solid tumors and the deadliest cancers in children. Approximately 10% of children with a CNS tumor harbor a hereditary cancer syndrome (HCS), but many will not be tested for a HCS. The Utah Population Database (UPDB) contains comprehensive cancer registry data for Utah families and can determine multigenerational cancer pedigrees across an archive of 5.8 million individuals. We hypothesize that the UPDB can identify children and families with HCSs not previously identified. Methods We queried the UPDB for individuals ages 0–39 diagnosed with a primary CNS tumor (malignant and benign) between 1966–2017 and generated cancer pedigrees of 3 generations or more for probands, extending to at least third-degree relatives. Specialized software calculated a familial standardized incidence ratio (FSIR) to determine families with excess clustering of CNS tumors. Clinical cancer genetics experts reviewed pedigrees to confirm patterns of HCS. Results We identified 4,634 CNS tumors in 4,550 individuals, of whom 2,233 (49%) reside in high-quality pedigrees containing ≥2 grandparents, at least 1 from both maternal and paternal sides. To identify families with excess clustering of CNS tumors, we selected pedigrees with an FSIR P&lt;0.05 and ≥2 affected patients, resulting in 161 high-risk families with a mean of 170 (median 96) relatives per pedigree of 3–6 generations. Among these 161 families, there were 2,017 unique relatives (first-third degree) of CNS probands with 2,355 tumors (any site), for a per pedigree average of 14.7 tumors in 12.5 relatives. Review of the 10 highest risk pedigrees indicated that 4 meet HCS criteria, including Li-Fraumeni (n=2), von Hippel-Lindau (n=1), and rhabdoid tumor predisposition (n=1). Conclusion The UPDB can produce multigenerational cancer pedigrees that identify individuals and families at risk of harboring a HCS who warrant germline testing. These findings should encourage clinicians to perform thorough family history screening.

The impact of a positive family history on clinical and pathologic outcomes of active surveillance for prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 225-225
Author(s):  
Adam Schneider ◽  
Nicholas Bowler ◽  
Ryan Fogg ◽  
Joon Yau Leong ◽  
Andrew Gusev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Hereditary Cancer ◽  
Positive Family History ◽  
Hereditary Cancer Syndrome ◽  
Strong Family History ◽  
Cancer Syndrome ◽  
Increased Risk ◽  
History Of ◽  
The Impact

225 Background: Active surveillance (AS) is the preferred management strategy for men with low-risk prostate cancer. However, approximately one in three men on AS experience progression of disease leading to treatment within 5 years, highlighting an urgent unmet need to reliably distinguish indolent from aggressive prostate cancer and improve patient selection criteria for AS. Germline genetic testing for DNA repair gene mutations is now recommended for patients with newly diagnosed prostate cancer and a strong family history of prostate cancer or BRCA1/2-related cancers, as such mutations have been associated with more aggressive forms of the disease. Here, we investigated the impact of family history on AS outcomes, under the hypothesis that men at high genetic risk for prostate cancer are at greater risk for progression to treatment on AS. Methods: We retrospectively reviewed detailed family history data of 958 patients from our institutional database of men enrolled in AS between 1997-2019. Data on family history of prostate cancer and hereditary cancer syndrome ( BRCA1/2-related prostate, breast, ovarian and/or pancreatic cancers) were collected and integrated into a composite family history score incorporating the number of relatives with each cancer weighted by degree of relatedness. A strong family history was defined as a composite score representing > 1 first-degree relative equivalent. The primary outcome was biopsy progression and secondary outcomes were adverse pathologic features at prostatectomy and biochemical recurrence. Statistical analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: In univariate analysis, a strong family history suggestive of a hereditary cancer syndrome (HR 1.37 [1.03-1.90], P = 0.033) was associated with a significant increased risk of biopsy progression; however, any family history of prostate cancer (HR 1.10 [0.89-1.35], P = 0.38) and a strong family history of prostate cancer (HR 1.35 [0.92-1.98], P = 0.13) were not significant. In multivariate analysis, a strong family history suggestive of a hereditary cancer syndrome remained a statistically significant predictor of biopsy progression (HR 1.42 [1.03-1.96], P = 0.03), after adjusting for age, percent core involvement on initial biopsy and PSA density. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. Conclusions: A positive family history suggestive of a hereditary cancer syndrome is associated with an increased risk of biopsy progression on AS and is an independent predictor of biopsy progression. Men with such a family history may still be safely offered AS but should be counseled about the higher risk of progression. Further work to investigate the underlying genetic factors responsible for this increased risk is warranted.

Genetic Characterization of Hereditary Cancer Syndromes Based on Targeted Next-Generation Sequencing

2021 ◽  
pp. 1-9
Author(s):  
Pelin Ercoskun ◽  
Cigdem Yuce Kahraman ◽  
Guller Ozkan ◽  
Abdulgani Tatar
Keyword(s):  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Genetics And Genomics ◽  
Cancer Syndromes ◽  
Generation Sequencing

A hereditary cancer syndrome is a genetic predisposition to cancer caused by a germline mutation in cancer-related genes. Identifying the disease-causing variant is important for both the patient and relatives at risk in cancer families because this could be a guide in treatment and secondary cancer prevention. In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Sequencing files were fed into a cloud-based data analysis pipeline. Reportable variants were classified according to the American College of Medical Genetics and Genomics guidelines. Three hundred five individuals were included in the study. Different pathogenic/likely pathogenic variants were detected in 75 individuals. The majority of these variants were in the <i>MUTYH</i>, <i>BRCA2</i>, and <i>CHEK2</i> genes. Nine novel pathogenic/likely pathogenic variants were identified in <i>BRCA1</i>, <i>BRCA2</i>, <i>GALNT12</i>, <i>ATM</i>, <i>MLH1</i>, <i>MSH2</i>, <i>APC</i>, and <i>KIT</i> genes. We obtained interesting and novel variants which could be related to hereditary cancer, and this study confirmed that NGS is an indispensable method for the risk assessment in cancer families.

scholarly journals Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort

2022 ◽  
Vol 11 ◽  
Author(s):  
Van Thuan Tran ◽  
Sao Trung Nguyen ◽  
Xuan Dung Pham ◽  
Thanh Hai Phan ◽  
Van Chu Nguyen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Hereditary Cancer ◽  
Carrier Frequency ◽  
Hereditary Cancer Syndromes ◽  
Cancer Syndrome ◽  
Pathogenic Variants ◽  
History Of ◽  
Cancer Syndromes ◽  
History Of Cancer

BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C&gt;T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C&gt;A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.

scholarly journals Characteristics and genetic testing outcomes of patients with clinically suspected paraganglioma/pheochromocytoma (PGL/PCC) syndrome in Singapore

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kay Reen Ting ◽  
Pei Yi Ong ◽  
Samuel Ow Guan Wei ◽  
Rajeev Parameswaran ◽  
Chin Meng Khoo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cancer Genetics ◽  
Chinese Patients ◽  
Hereditary Cancer Syndrome ◽  
Limited Data ◽  
Cancer Syndrome ◽  
Causative Gene ◽  
Asian Patients ◽  
Pathogenic Variants ◽  
History Of

Abstract Background Hereditary paraganglioma (PGL) and pheochromocytoma (PCC) syndromes are rare conditions, with limited data on spectrum of causative gene variants of these syndromes in Asian patients. Methods We describe the clinical characteristics and genetic testing outcomes of patients with suspected hereditary PGL/PCC who were referred to a tertiary cancer genetics clinic in Singapore. Results Among 2196 patients with suspected hereditary cancer syndrome evaluated at the cancer genetics clinic from 2000 to 2019, 13/2196 (0.6%) patients fulfilled clinical suspicion for hereditary PGL/PCC syndrome. After genetic counselling, 10 patients underwent multi-gene next generation sequencing and deletion/duplication analysis, including SDHAF2, SDHA, SDHB, SDHC, SDHD, VHL, NF1, RET, MAX, and TMEM127. Seven of 10 patients (70%) were identified to carry pathogenic variants, including 3 unrelated Chinese patients with head and neck PGL who carried the same SDHD: c.3G > C (p.Met1Ile) variant that was previously reported to be a possible founder variant in Chinese, and 3 patients with urogenital PGL and 1 patient with retroperitoneal PGL who carried different SDHB variants. Variant carriers were younger, more likely to present with multiple tumours, or have family history of paraganglioma or pheochromocytoma, than non- variant carriers. Conclusion Hereditary PGL/PCC accounts for only 0.6% of patients seen in an adult cancer genetics clinic in Asia. SDHD and SDHB genes remain the most important causative genes of hereditary PGL/PCC in Asia even when patients are tested with multi-gene NGS panel.

scholarly journals Current Testing Guidelines: A Retrospective Analysis of a Community-Based Hereditary Cancer Program

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Margaret Ward, DNP, APRN, AGNP-BC ◽  
Betty Elder, PhD, RN ◽  
Maryon Habtemariam, DNP, APRN
Keyword(s):  
Genetic Testing ◽  
Retrospective Analysis ◽  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Hereditary Cancer Syndromes ◽  
Cancer Syndrome ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Preventative Measures ◽  
Cancer Syndromes

It is estimated that 5% to 10% of all cancers are related to a hereditary cancer syndrome. However, specific cancers, such as pancreatic and ovarian cancers, are related to hereditary cancer syndromes 15% to 20% of the time. Genetic testing guidelines for hereditary cancer syndromes are frequently reviewed and updated by the National Comprehensive Cancer Network (NCCN). The purpose of this retrospective analysis is to identify carriers of pathogenic variants or hereditary cancer syndrome who do not meet NCCN criteria for testing and compare the results with previous studies. The data obtained can be used to provide recommendations to assess current guidelines for testing and evaluate the benefit of comprehensive panel testing vs. standard testing for specific hereditary cancer syndromes. This project is a retrospective review of clinical histories of patients who had multigene panel testing between September 2015 and February 2019 through a cancer outreach and risk assessment (CORA) program. Frequencies analyses were performed to analyze results. A total of 233 individuals were included in the analysis: 171 met BRCA1/2 testing criteria, 66 met Lynch syndrome criteria, and 4 met polyposis criteria. Of the individuals meeting established criteria for testing, 39 were identified with pathogenic variants. However, only 10 of these individuals were identified with a pathogenic variant associated with the criteria for which they met. Genetic testing that is limited to only those patients with genes associated with hereditary cancer syndromes may lead to exclusion of other potentially actionable genes, which may impair a patient’s ability to receive additional screening or preventative measures.

scholarly journals Significance of defining a pathogenic variant in hereditary cancer syndrome

2017 ◽  
Vol 3 (3) ◽  
Author(s):  
Kwong-Kwok Wong
Keyword(s):  
Hereditary Cancer ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Cancer Genetics ◽  
Hereditary Cancer Syndrome ◽  
Gastrointestinal Cancers ◽  
Cancer Syndrome ◽  
Cancer Family ◽  
Extended Pedigrees ◽  
Hereditary Nonpolyposis

<p>With the advances in cancer genetics, over 200 hereditary cancer susceptibility syndromes have been described. About 5%–10% of all cancers are caused by hereditary mutations. The most common syndromes are those associated with breast, ovarian and gastrointestinal cancers. The hereditary pattern of stomach and endometrial cancer was first reported by Warthin in 1931. In 1966, Lynch and colleagues reported studies of two extended pedigrees with a similar hereditary pattern of multiple carcinomas and this was designated a cancer family syndrome. This condition was subsequently called hereditary nonpolyposis colorectal cancer (HNPCC). However, the term “Lynch syndrome” has been commonly used to describe this condition since 1984.</p>

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