Browsing by Author "Syngal, Sapna"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO
    (Springer Nature, 2021) Blackford, Amanda L.; Childs, Erica J.; Porter, Nancy; Petersen, Gloria M.; Rabe, Kari G.; Gallinger, Steven; Borgida, Ayelet; Syngal, Sapna; Cote, Michele L.; Schwartz, Ann G.; Goggins, Michael G.; Hruban, Ralph H.; Parmigiani, Giovanni; Klein, Alison P.; Epidemiology, Richard M. Fairbanks School of Public Health
    Introduction: Identifying families with an underlying inherited cancer predisposition is a major goal of cancer prevention efforts. Mendelian risk models have been developed to better predict the risk associated with a pathogenic variant of developing breast/ovarian cancer (with BRCAPRO) and the risk of developing pancreatic cancer (PANCPRO). Given that pathogenic variants involving BRCA2 and BRCA1 predispose to all three of these cancers, we developed a joint risk model to capture shared susceptibility. Methods: We expanded the existing framework for PANCPRO and BRCAPRO to jointly model risk of pancreatic, breast, and ovarian cancer and validated this new model, BRCAPANCPRO on three data sets each reflecting the common target populations. Results: BRCAPANCPRO outperformed the prior BRCAPRO and PANCPRO models and yielded good discrimination for differentiating BRCA1 and BRCA2 carriers from non-carriers (AUCs 0.79, 95% CI: 0.73-0.84 and 0.70, 95% CI: 0.60-0.80) in families seen in high-risk clinics and pancreatic cancer family registries, respectively. In addition, BRCAPANCPRO was reasonably well calibrated for predicting future risk of pancreatic cancer (observed-to-expected (O/E) ratio = 0.81 [0.69, 0.94]). Discussion: The BRCAPANCPRO model provides improved risk assessment over our previous risk models, particularly for pedigrees with a co-occurrence of pancreatic cancer and breast and/or ovarian cancer.
  • Thumbnail Image
    Item
    Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines
    (Elsevier, 2023) Cavestro, Giulia Martina; Mannucci, Alessandro; Balaguer, Francesc; Hampel, Heather; Kupfer, Sonia S.; Repici, Alessandro; Sartore-Bianchi, Andrea; Seppälä, Toni T.; Valentini, Vincenzo; Boland, Clement Richard; Brand, Randall E.; Buffart, Tineke E.; Burke, Carol A.; Caccialanza, Riccardo; Cannizzaro, Renato; Cascinu, Stefano; Cercek, Andrea; Crosbie, Emma J.; Danese, Silvio; Dekker, Evelien; Daca-Alvarez, Maria; Deni, Francesco; Dominguez-Valentin, Mev; Eng, Cathy; Goel, Ajay; Guillem, Josè G.; Houwen, Britt B. S. L.; Kahi, Charles; Kalady, Matthew F.; Kastrinos, Fay; Kühn, Florian; Laghi, Luigi; Latchford, Andrew; Liska, David; Lynch, Patrick; Malesci, Alberto; Mauri, Gianluca; Meldolesi, Elisa; Møller, Pål; Monahan, Kevin J.; Möslein, Gabriela; Murphy, Caitlin C.; Nass, Karlijn; Ng, Kimmie; Oliani, Cristina; Papaleo, Enrico; Patel, Swati G.; Puzzono, Marta; Remo, Andrea; Ricciardiello, Luigi; Ripamonti, Carla Ida; Siena, Salvatore; Singh, Satish K.; Stadler, Zsofia K.; Stanich, Peter P.; Syngal, Sapna; Turi, Stefano; Urso, Emanuele Damiano; Valle, Laura; Vanni, Valeria Stella; Vilar, Eduardo; Vitellaro, Marco; You, Yi-Qian Nancy; Yurgelun, Matthew B.; Zuppardo, Raffaella Alessia; Stoffel, Elena M.; Associazione Italiana Familiarità Ereditarietà Tumori; Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; European Hereditary Tumour Group; International Society for Gastrointestinal Hereditary Tumours; Medicine, School of Medicine
    Background & aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.
  • Thumbnail Image
    Item
    Inherited DNA-Repair Defects in Colorectal Cancer
    (Elsevier, 2018-03-01) AlDubayan, Saud H.; Giannakis, Marios; Moore, Nathanael D.; Han, G. Celine; Reardon, Brendan; Hamada, Tsuyoshi; Mu, Xingmeng Jasmine; Nishihara, Reiko; Qian, Zhirong; Liu, Li; Yurgelun, Matthew B.; Syngal, Sapna; Garraway, Levi A.; Ogino, Shuji; Fuchs, Charles S.; Van Allen, Eliezer M.; Medicine, School of Medicine
    Colorectal cancer (CRC) heritability has been estimated to be around 30%. However, mutations in the known CRC-susceptibility genes explain CRC risk in fewer than 10% of affected individuals. Germline mutations in DNA-repair genes (DRGs) have recently been reported in CRC, but their contribution to CRC risk is largely unknown. We evaluated the gene-level germline mutation enrichment of 40 DRGs in 680 unselected CRC individuals and 27,728 ancestry-matched cancer-free adults. Significant findings were then examined in independent cohorts of 1,661 unselected CRC individuals and 1,456 individuals with early-onset CRC. Of the 680 individuals in the discovery set, 31 (4.56%) individuals harbored germline pathogenic mutations in known CRC-susceptibility genes, and another 33 (4.85%) individuals had DRG mutations that have not been previously associated with CRC risk. Germline pathogenic mutations in ATM and PALB2 were enriched in both the discovery (OR = 2.81 and p = 0.035 for ATM and OR = 4.91 and p = 0.024 for PALB2) and validation (OR = 2.97 and adjusted p = 0.0013 for ATM and OR = 3.42 and adjusted p = 0.034 for PALB2) sets. Biallelic loss of ATM was evident in all individuals with matched tumor profiling. CRC individuals also had higher rates of actionable mutations in the HR pathway, which can substantially increase the risk of developing cancers other than CRC. Our analysis provides evidence for ATM and PALB2 as CRC-risk genes, underscoring the importance of the homologous recombination pathway in CRC. In addition, we identified frequent complete homologous recombination deficiency in CRC tumors, representing a unique opportunity to explore targeted therapeutic interventions such as poly-ADP ribose polymerase inhibitor (PARPi).
  • Thumbnail Image
    Item
    Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer
    (Elsevier, 2020-03) Gupta, Samir; Lieberman, David; Anderson, Joseph C.; Burke, Carol A.; Dominitz, Jason A.; Kaltenbach, Tonya; Robertson, Douglas J.; Shaukat, Aasma; Syngal, Sapna; Rex, Douglas K.; Medicine, School of Medicine
  • Thumbnail Image
    Item
    Spotlight: US Multi-Society Task Force on Colorectal Cancer Recommendations for Follow-up After Colonoscopy and Polypectomy
    (Elsevier, 2020-03) Gupta, Samir; Lieberman, David; Anderson, Joseph C.; Burke, Carol A.; Dominitz, Jason A.; Kaltenbach, Tonya; Robertson, Douglas J.; Shaukat, Aasma; Syngal, Sapna; Rex, Douglas K.; Medicine, School of Medicine