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<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.

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 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.

Analysis of von Hippel–Lindau Hereditary Cancer Syndrome: Implications of Oxygen Sensing

2004 ◽  
pp. 320-335 ◽  
Author(s):  
Haifeng Yang ◽  
Mircea Ivan ◽  
Jung-Hyun Min ◽  
William Y Kim ◽  
William G Kaelin
Keyword(s):  
Hereditary Cancer ◽  
Oxygen Sensing ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome ◽  
Von Hippel Lindau

Multi-gene panel testing of patients with multiple primary malignancies suspected with hereditary cancer syndrome.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1512-1512
Author(s):  
Gloria HJ Chan ◽  
Pei Yi Ong ◽  
Jeffrey JH Low ◽  
Hwai L. Kong ◽  
Samuel Guan Wei Ow ◽  
...  
Keyword(s):  
Hereditary Cancer ◽  
Cancer Genetics ◽  
Hereditary Cancer Syndrome ◽  
Primary Cancer ◽  
Deleterious Mutations ◽  
Cancer Syndrome ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Multiple Primary ◽  
The Mean

1512 Background: Developing multiple primary cancers is an indicator of underlying hereditary cancer predisposition, but there is a paucity of data regarding the characteristics and clinical genetic testing outcome of these patients. Methods: We compared cancer index patients with 1 vs > 1 primary malignancy who underwent evaluation and clinical testing with multi-gene panels comprising up to 49 genes in a cancer genetics clinic in a tertiary cancer centre in Asia from 1998-2016. Results: Among 1191 cancer index patients, 960 (80.6%), 205 (17.2%), and 26 (2.2%) respectively had 1, 2, and ≥3 primary malignancies. Among patients with > 1 primary cancers (n = 231), the most common cancer pairs were breast-breast (35.4%), breast-ovary (12.1%), endometrium-ovary (8.2%), colon-colon (2.4%) and, colon-endometrium (2.4%). The mean age at diagnosis of the first, second and third cancers were 46.0 (21 to 87), 52.1 (21 to 89) and 57.7 (41 to 83) respectively. The mean duration between first and second cancers is 6.0 years (0 to 32). The most commonly suspected syndromes in patients with 1 vs > 1 primary cancer were hereditary breast and ovarian cancer 63.8% vs 53.6%, Lynch 24.8% vs 31.1%, Li-Fraumeni syndromes 1.8% vs 1.7%, and others 9.3% vs 13.4% (p = 0.03). Patients with > 1 primary cancer were more likely to have > 20% a priori risk of suspected hereditary cancer syndrome (42.8% vs. 26.5%; p < 0.001). 504/1191 (42.3%) patients underwent gene testing, including 394/960 (41.0%) and 110/231 (47.6%) patients with 1 vs > 1 cancer. Deleterious mutations were more likely to be identified in patients with > 1 vs 1 cancer (34.5% vs. 25.8%; p = 0.073), with causative genes being BRCA1 38.5%, BRCA2 17.9%, MLH1/MSH2/MSH6 20.5%, TP53 7.7%, and others (ATM [n = 2], MUTYH, APC, PALB2, RAD51 [n = 1 each]) for patients with > 1 cancer. VUS rates were 31.7% vs.31.8% in patients with 1 vs > 1 cancer, and were identified in genes including BRIP1, CHEK2, PALLD, POLE, PTEN, STK11, SMARCA4, and VHL. Conclusions: Patients with > 1 primary cancer comprised one-fifth of cancer index patients evaluated at a cancer genetics clinic, and were more likely to be found with deleterious mutations than patients with only 1 cancer on multi-gene panel testing.

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>

Thymoma associated with malignancies may herald a hereditary cancer syndrome

2010 ◽  
Vol 9 (4) ◽  
pp. 655-657 ◽  
Author(s):  
Omid Saeed Tehrani ◽  
Emily Q. Chen ◽  
David L. Schaebler ◽  
Abdul W. Mughal
Keyword(s):  
Hereditary Cancer ◽  
Hereditary Cancer Syndrome ◽  
Cancer Syndrome

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.

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