دورية أكاديمية
High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.
| العنوان: | High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer. |
|---|---|
| المؤلفون: | Bannon SA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas., Montiel MF; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas., Goldstein JB; Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Dong W; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Mork ME; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas., Borras E; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas., Hasanov M; Internal Medicine Department, The University of Texas Health Science Center at Houston, Houston, Texas., Varadhachary GR; Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Maitra A; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Katz MH; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Feng L; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Futreal A; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Fogelman DR; Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Vilar E; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., McAllister F; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, Texas. fmcallister@mdanderson.org.; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. |
| المصدر: | Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2018 Nov; Vol. 11 (11), pp. 679-686. Date of Electronic Publication: 2018 Oct 01. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101479409 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1940-6215 (Electronic) Linking ISSN: 19406215 NLM ISO Abbreviation: Cancer Prev Res (Phila) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research |
| مواضيع طبية MeSH: | Genetic Predisposition to Disease*, Carcinoma, Pancreatic Ductal/*genetics , Neoplastic Syndromes, Hereditary/*epidemiology , Pancreatic Neoplasms/*genetics, Adult ; Age Factors ; Age of Onset ; Aged ; Aged, 80 and over ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Carcinoma, Pancreatic Ductal/mortality ; Cohort Studies ; DNA Mismatch Repair/genetics ; DNA Mutational Analysis ; Female ; Genetic Counseling ; Humans ; Male ; Medical History Taking ; Middle Aged ; Neoplastic Syndromes, Hereditary/diagnosis ; Neoplastic Syndromes, Hereditary/genetics ; Pancreatic Neoplasms/mortality ; Prevalence ; Risk Factors ; Survival Analysis |
| مستخلص: | Introduction: We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis. Methods: Patients from two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations were determined, and clinical characteristics including survival were analyzed. Results: A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC [odds ratios (OR), 1.93 ± 1.03-3.70, P = 0.039] and GC (4.78 ± 1.10-32.95, P = 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR, 0.44; 95% CI of HR, 0.25-0.76, P = 0.030). Discussion: Germline mutations are highly prevalent in patients with PDAC of early onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset. Cancer Prev Res; 11(11); 679-86. ©2018 AACR . (©2018 American Association for Cancer Research.) |
| References: | J Natl Cancer Inst. 2017 Sep 1;109(9):. (PMID: 28954281) J Natl Cancer Inst. 2010 Jan 20;102(2):119-26. (PMID: 20068195) Science. 2009 Apr 10;324(5924):217. (PMID: 19264984) N Engl J Med. 2015 Jun 25;372(26):2509-20. (PMID: 26028255) Cancer. 2002 Jan 1;94(1):84-96. (PMID: 11815963) Cancer Discov. 2016 Aug;6(8):852-69. (PMID: 27246539) Gut. 2013 Mar;62(3):339-47. (PMID: 23135763) J Clin Oncol. 2015 Oct 1;33(28):3124-9. (PMID: 25940717) Cancer Res. 2002 Jul 1;62(13):3789-93. (PMID: 12097290) Gastroenterology. 2015 Mar;148(3):556-64. (PMID: 25479140) Oncogene. 2015 Apr 16;34(16):2052-60. (PMID: 24909166) J Clin Oncol. 2017 Oct 20;35(30):3382-3390. (PMID: 28767289) Am J Pathol. 1999 Jun;154(6):1835-40. (PMID: 10362809) Anticancer Res. 2011 Apr;31(4):1417-20. (PMID: 21508395) Cancer J. 2001 Jul-Aug;7(4):266-73. (PMID: 11561603) Cancer Res. 2004 Apr 1;64(7):2634-8. (PMID: 15059921) Gastroenterol Hepatol (N Y). 2017 May;13(5):268-275. (PMID: 28656024) Mol Carcinog. 2012 Jan;51(1):14-24. (PMID: 22162228) N Engl J Med. 1994 Jul 14;331(2):81-4. (PMID: 8208269) Cancer Epidemiol Biomarkers Prev. 2016 Jan;25(1):207-11. (PMID: 26483394) Cancer Res. 1996 Dec 1;56(23):5360-4. (PMID: 8968085) |
| معلومات مُعتمدة: | K12 CA088084 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (BRCA1 Protein) 0 (BRCA1 protein, human) 0 (BRCA2 Protein) 0 (BRCA2 protein, human) |
| تواريخ الأحداث: | Date Created: 20181003 Date Completed: 20190927 Latest Revision: 20200309 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6343472 |
| DOI: | 10.1158/1940-6207.CAPR-18-0014 |
| PMID: | 30274973 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1940-6215 |
|---|---|
| DOI: | 10.1158/1940-6207.CAPR-18-0014 |