Distinct Molecular Phenotype of Sporadic Colorectal Cancers Among Young Patients Based on Multiomics Analysis

Holowatyj, Andreana N.; Gigic, Biljana; Herpel, Esther; Scalbert, Augustin; Schneider, Martin; Ulrich, Cornelia M.; Achaintre, David; Brezina, Stefanie; Duijnhoven, Fränzel J.B. van; Gsur, Andrea; Keski‐Rahkonen, Pekka; Weijenberg, Matty P.; Abbenhardt-Martin, Clare; Boehm, Juergen; Boucher, Kenneth M.; Habermann, Nina; Haffa, Mariam; Hardikar, Sheetal; Himbert, Caroline; Kauczor, Hans‐Ulrich; Kloor, Matthias; Lampe, Paul D.; Lin, Tengda; Ose, Jennifer; Scherer, Dominique; Schirmacher, Peter; Schrotz‐King, Petra; Knebel‐Doeberitz, Magnus von; Warby, Christy A.; Zhang, Yuzheng; Ulrich, Alexis; Swanson, Eric A.; Tavtigian, Sean V.

doi:10.1053/j.gastro.2019.11.012

Cited by 46 publications

(43 citation statements)

References 20 publications

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“…However, to our knowledge, no studies to date have compared molecular phenotypes of AC by age at disease onset. Given the known molecular phenotypes unique to early-onset vs late-onset CRC, 15 , 16 we hypothesized that distinct etiologies also underlie the growing AC burden among young patients. The purpose of this study, comprised of patients from the international clinicogenomic data-sharing consortium American Association of Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE), 17 was to characterize distinct putative driver variations and genes between patients diagnosed with early-onset and late-onset AC.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age

et al. 2020

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Key Points Question What are the differences in somatic cancer gene variations in appendiceal cancer among adults based on age at disease onset? Findings In this cohort study of 385 patients diagnosed with appendiceal cancer with targeted clinical-grade sequencing data from the American Association for Cancer Project Genomics Evidence Neoplasia Information Exchange, patients who were diagnosed at age younger than 50 years harbored unique somatic variant patterns in PIK3CA , GNAS , SMAD3 , and TSC2 compared with those diagnosed at age 50 years and older. Meaning These findings suggest that appendiceal cancer diagnosed among young individuals harbors a distinct spectrum of somatic variations, which may yield clinical actionability in the development of targeted therapeutic modalities for young patients with appendiceal cancer.

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Section: Introductionmentioning

confidence: 99%

Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age

et al. 2020

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“…Hypomethylation of LINE-1 elements also appears to be more frequent in tumors from patients under age 50 [ 112 ], suggesting unique methylation patterns in early-onset CRC. A multi-omics study demonstrated a unique signature in oxidative stress response in early-onset CRC [ 113 ].…”

Section: Tumor Characteristics and Disparitiesmentioning

confidence: 99%

Disparities in Early-Onset Colorectal Cancer

Muller

Ihionkhan

Stoffel

et al. 2021

Cells

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The incidence and mortality of early-onset colorectal cancer (CRC) are increasing in the United States (US) and worldwide. In the US, there are notable disparities in early-onset CRC burden by race/ethnicity and geography. African Americans, Hispanic/Latinos, and populations residing in specific regions of the Southern U.S. are disproportionately affected with CRC diagnosed at younger ages, while less is known about disparities in other countries. Reasons for these disparities are likely multi-factorial and potentially implicate differences in health determinants including biology/genetics, diet/environment, individual health behaviors, and access to high-quality health services, as well as social and policy factors. This review summarizes current understanding of early-onset CRC disparities and identifies specific research areas that will inform evidence-based interventions at individual, practice, and policy levels to reduce the global burden of this disease.

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“…Lieu et al (2019) discovered that tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration 11 . However, Holowatyj et al (2020) among others have shown that early‐onset colorectal cancer harbors distinct biology including more genetic variants and distinct molecular phenotype indicating the need for further studies to determine the exact etiology of early‐onset colorectal cancer 12 …”

Section: Introductionmentioning

confidence: 99%

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients

et al. 2021

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Background The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. Methods We identified 6708 young adults aged 18–45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan–Meier estimation, log rank test, and multivariate Cox proportional hazards model. Results Sixty‐three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31–0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43–0.49, p < 0.001 and HR 0.64, 95% CI: 0.55–0.76, p < 0.001, respectively). Conclusion This is the largest observational study to evaluate survival outcomes in young‐onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.

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Distinct Molecular Phenotype of Sporadic Colorectal Cancers Among Young Patients Based on Multiomics Analysis

Cited by 46 publications

References 20 publications

Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age

Spectrum of Somatic Cancer Gene Variations Among Adults With Appendiceal Cancer by Age

Disparities in Early-Onset Colorectal Cancer

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients

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