The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database
Abstract Background IDH1/2 mutated glioma has been associated with a germline risk variant, the rs55705857 G allele. The Utah Population Database (UPDB), a computerized genealogy of people in Utah, is a unique resource to evaluate cancer risk in related individuals. Methods One hundred and two indiv...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-019-5381-2 |
| _version_ | 1818522169937756160 |
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| author | Sarah Hummel Wendy Kohlmann Thomas M. Kollmeyer Robert Jenkins Joshua Sonnen Cheryl A. Palmer Howard Colman Diana Abbott Lisa Cannon-Albright Adam L. Cohen |
| author_facet | Sarah Hummel Wendy Kohlmann Thomas M. Kollmeyer Robert Jenkins Joshua Sonnen Cheryl A. Palmer Howard Colman Diana Abbott Lisa Cannon-Albright Adam L. Cohen |
| author_sort | Sarah Hummel |
| collection | DOAJ |
| description | Abstract Background IDH1/2 mutated glioma has been associated with a germline risk variant, the rs55705857 G allele. The Utah Population Database (UPDB), a computerized genealogy of people in Utah, is a unique resource to evaluate cancer risk in related individuals. Methods One hundred and two individuals with IDH1/2 mutant or 1p/19q co-deleted glioma were genotyped and linked to the UPDB. DNA came from blood (21), tumor tissue (43), or both (38). We determined congruence between somatic and germline samples and estimated the relative risk for developing cancer to first and second-degree relatives of G and A allele carriers at rs55705857. Results Somatic (glioma) DNA had 85.7% sensitivity (CI 57.2–98.2%) and 95.8% specificity (CI 78.9–99.89%) for germline rs55705857 G allele. Forty-one patients were linked to pedigrees in the UPDB with at least three generations of data. First-degree relatives of rs55705857 G allele carriers were at significantly increased risk for developing cancer (RR = 1.72, p = 0.045, CI 1.02–2.94), and specifically for oligodendroglioma (RR = 57.61, p = 0.017, CI 2.96–320.98) or prostate cancer (RR = 4.10, p = 0.008, CI 1.62–9.58); relatives of individuals without the G allele were not at increased risk. Second-degree relatives of G allele carriers also had significantly increased risk for developing cancer (RR = 1.50, p = 0.007, CI 1.15–2.01). Conclusions Tumor DNA may approximate genotype at the rs55705857 locus. We confirmed this locus confers an increased risk of all cancers and especially of oligodendroglioma. No increased cancer or brain tumor risk is seen in family members of individuals without the high-risk G allele. |
| first_indexed | 2024-12-11T05:29:45Z |
| format | Article |
| id | doaj.art-ab2501c8329a4d46824e64063692d3de |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T05:29:45Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-ab2501c8329a4d46824e64063692d3de2022-12-22T01:19:27ZengBMCBMC Cancer1471-24072019-03-011911610.1186/s12885-019-5381-2The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population databaseSarah Hummel0Wendy Kohlmann1Thomas M. Kollmeyer2Robert Jenkins3Joshua Sonnen4Cheryl A. Palmer5Howard Colman6Diana Abbott7Lisa Cannon-Albright8Adam L. Cohen9Department of Human Genetics/Pediatric Division of Medical Genetics, Graduate Program in Genetic Counseling, University of Utah School of MedicineDepartment of Population Sciences, University of Utah School of Medicine, Huntsman Cancer InstituteThe Mayo Clinic, Department of Laboratory Medicine and PathologyThe Mayo Clinic, Department of Laboratory Medicine and PathologyDivision of Anatomic Pathology, University of Utah School of MedicineDivision of Anatomic Pathology, University of Utah School of MedicineDepartment of Neurosurgery, University of Utah School of Medicine, Huntsman Cancer InstituteDivision of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of MedicineGeorge E. Wahlen Department of Veterans Affairs Medical CenterDivision of Oncology, University of Utah School of Medicine, Huntsman Cancer InstituteAbstract Background IDH1/2 mutated glioma has been associated with a germline risk variant, the rs55705857 G allele. The Utah Population Database (UPDB), a computerized genealogy of people in Utah, is a unique resource to evaluate cancer risk in related individuals. Methods One hundred and two individuals with IDH1/2 mutant or 1p/19q co-deleted glioma were genotyped and linked to the UPDB. DNA came from blood (21), tumor tissue (43), or both (38). We determined congruence between somatic and germline samples and estimated the relative risk for developing cancer to first and second-degree relatives of G and A allele carriers at rs55705857. Results Somatic (glioma) DNA had 85.7% sensitivity (CI 57.2–98.2%) and 95.8% specificity (CI 78.9–99.89%) for germline rs55705857 G allele. Forty-one patients were linked to pedigrees in the UPDB with at least three generations of data. First-degree relatives of rs55705857 G allele carriers were at significantly increased risk for developing cancer (RR = 1.72, p = 0.045, CI 1.02–2.94), and specifically for oligodendroglioma (RR = 57.61, p = 0.017, CI 2.96–320.98) or prostate cancer (RR = 4.10, p = 0.008, CI 1.62–9.58); relatives of individuals without the G allele were not at increased risk. Second-degree relatives of G allele carriers also had significantly increased risk for developing cancer (RR = 1.50, p = 0.007, CI 1.15–2.01). Conclusions Tumor DNA may approximate genotype at the rs55705857 locus. We confirmed this locus confers an increased risk of all cancers and especially of oligodendroglioma. No increased cancer or brain tumor risk is seen in family members of individuals without the high-risk G allele.http://link.springer.com/article/10.1186/s12885-019-5381-2Molecular epidemiologyIDHrs55705857OligodendrogliomaCancer |
| spellingShingle | Sarah Hummel Wendy Kohlmann Thomas M. Kollmeyer Robert Jenkins Joshua Sonnen Cheryl A. Palmer Howard Colman Diana Abbott Lisa Cannon-Albright Adam L. Cohen The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database BMC Cancer Molecular epidemiology IDH rs55705857 Oligodendroglioma Cancer |
| title | The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database |
| title_full | The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database |
| title_fullStr | The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database |
| title_full_unstemmed | The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database |
| title_short | The contribution of the rs55705857 G allele to familial cancer risk as estimated in the Utah population database |
| title_sort | contribution of the rs55705857 g allele to familial cancer risk as estimated in the utah population database |
| topic | Molecular epidemiology IDH rs55705857 Oligodendroglioma Cancer |
| url | http://link.springer.com/article/10.1186/s12885-019-5381-2 |
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