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Wiley MB, Bauer J, Alvarez V, Kolics Z, Cheng W, Church DN, Kerr DJ, Kerr RS, Jung B. Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner. Sci Rep 2025; 15:8509. [PMID: 40075112 PMCID: PMC11903883 DOI: 10.1038/s41598-025-91853-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
Advanced colorectal cancer (CRC) continues to present with poor survival and treatment options remain limited. We have shown that increased activin A (activin) expression in the tumor microenvironment (TME) is associated with poor outcome in a cohort of stage III and IV CRC patients. Here, we hypothesized that activin promotes stage specific outcomes in CRC, enhancing metastasis and tolerance in late-stage CRC exclusively. We employed Digital Spatial Profiling (DSP) technology on a cohort of stage II and III CRC patient tissue samples obtained at the time of curative surgery to show that activin co-localization was associated with increased mitogenic signaling, proliferation, and immunosuppression in stage III, but not stage II, CRCs. Furthermore, we found strong linear correlations between markers of immunosuppression and signaling proteins in activin (+) areas, an effect that was not observed in activin (-) areas of tissue. Taken together these data suggest activin exerts pro-metastatic and immunosuppressive effects in stage III, but not stage II, CRC providing an attractive therapeutic target for advanced CRC.
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Affiliation(s)
- Mark B Wiley
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Jessica Bauer
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Valentina Alvarez
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Zoe Kolics
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Wenxuan Cheng
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - David N Church
- Nuffield Department of Medicine, University of Oxford, Oxford, OX1 4BH, UK
- NIHR Oxford Comprehensive Biomedical Research Center, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, OX1 4BH, UK
| | - David J Kerr
- Radcliffe Department of Medicine, University of Oxford, Oxford, OX1 4BH, UK
| | - Rachel S Kerr
- Department of Oncology, University of Oxford, Oxford, OX1 4BH, UK
| | - Barbara Jung
- School of Medicine, University of California, San Diego, San Diego, CA, 92093, USA.
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Meldolesi E, Nicolì A, Dinapoli N, Chiloiro G, Romano A, Menghi R, Persiani R, Pacelli F, Coco C, Ratto C, Manfrida S, Boldrini L, Corvari B, Gambacorta M. E_N_T_R_O_P_Y: Monocentric analysis of rectal cancer radio-chemotherapy treatment in patients of young age. Clin Transl Radiat Oncol 2025; 51:100905. [PMID: 39886541 PMCID: PMC11780713 DOI: 10.1016/j.ctro.2024.100905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 12/16/2024] [Accepted: 12/20/2024] [Indexed: 02/01/2025] Open
Abstract
Purpose//objectives A disproportionate incidence's increase of rectal cancer in patients younger than 50 years of age. The ESMO and NCCN recommendations are not age-specific and the literature is poor and conflicting. We decided to examine patients with rectal cancer treated in our centre in the last 15 years with curative neoadjuvant radiochemotherapy comparing outcomes in the two groups under and over 55 years old. Materials/methods 788 rectal cancer patients were enrolled in this monocentric retrospective observational study (523 =>55 years and 265 < 55). All patients received neoadjuvant chemoradiation treatment. R statistical software v.4.1.3 was used for the entire analysis. The outcomes were death, local recurrence, and new distant metastases. Survival analysis was performed using the Kaplan-Meier method and the Log-rank was used to compare the two groups. Results All patients were classified in different risk groups, according to the ESMO 2017 rectal cancer clinical practice guidelines. 88 % of patients under 55 years old at the diagnosis belonged to the bad or advanced risk groups with an equal division. In patients over 55 years old, there was a clear dominance of the advanced risk class (62 % of the total). In multivariate analysis, OS and DFS decrease with increasing age and ESMO risk group. The other variables in multivariate were not significant. For Both OS, DFS and MFS, the curves separated significantly at 55 years of age, with a prevalence of metastasis development in the older group. Conclusion Elderly patients have a prevalence of advanced disease. Younger patients seem having a better OS at 3 and 5 years. ESMO risk group and age were the only variables affecting OS and DFS. Young patients have better MFS and DFS at 2 and 5 years than patients older than 55 years. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemotherapy resulted not significant in both groups.
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Affiliation(s)
- E. Meldolesi
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - A. Nicolì
- Department of Palliative Care, ASL Lecce, San Cesario di Lecce, Lecce, Italy
| | - N. Dinapoli
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - G. Chiloiro
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - A. Romano
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - R. Menghi
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - R. Persiani
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - F. Pacelli
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - C. Coco
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
| | - C. Ratto
- Proctology and Pelvic Floor Surgery Unit, Center of Excellence for Gastrointestinal and Endocrine-Metabolic Diseases, Isola Tiberina - Gemelli Isola Hospital, Rome, Italy
| | - S. Manfrida
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - L. Boldrini
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - B. Corvari
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - M.A. Gambacorta
- Department of Diagnostic Imaging, Radiation Oncology and Haematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
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Kraus SG, Johnson KA, Emmerich PB, Clipson L, Pasch CA, Zhang W, Matkowskyj KA, Deming DA. Micro-environmental changes indicate potential for subclinical intestinal tissue damage in early-age-onset colorectal cancer patients. Gastroenterol Rep (Oxf) 2025; 13:goaf015. [PMID: 39980836 PMCID: PMC11842056 DOI: 10.1093/gastro/goaf015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 12/17/2024] [Accepted: 01/14/2025] [Indexed: 02/22/2025] Open
Abstract
Background While improved screening rates have contributed to an overall decrease in the incidence of colorectal cancer (CRC), the incidence of early-age-onset CRC (EAO CRC; age <50 years) has increased. Here, we characterize the genetic alterations and tumor microenvironment (TME) for EAO and later-age-onset (LAO) CRCs to identify relevant biological differences that might point to etiologic factors. Methods A cohort of EAO (n = 60) and LAO (n = 93) CRC patients were evaluated for mutations by using targeted DNA sequencing and for TME differences by using immunohistochemistry and immunofluorescence. The Cancer Genome Atlas (TCGA) PanCancer Atlas colorectal adenocarcinoma cohort was evaluated for transcriptional changes between EAO (n = 82) and LAO (n = 510) patients. Results KRAS and BRAF mutations were less frequent in EAO CRCs. Gene-set enrichment analysis of TCGA data revealed the downregulation of immune-related pathways in EAO CRCs. Both age cohorts had similar numbers of CD8+ tumor-infiltrating lymphocytes (TILs), although LAO patients had more CD4+ TILs and Th1-polarized CD4s. While significant associations between immune subsets and versican (VCAN), versikine, and alpha-smooth muscle actin (αSMA) were found, none of these trends differed between age cohorts. EAO patients trended towards greater VCAN accumulation in adjacent normal tissue, lower rates of VCAN proteolysis, and decreased αSMA accumulation vs LAO patients. Conclusions Overall, established EAO cancers are similar to LAO cancers in mutational profile and key TME features. High VCAN and αSMA expression in adjacent normal colon indicates a presence of factors that are associated with increased intestinal subclinical inflammation. Future mechanistic studies will be conducted to better understand the importance of these findings and related processes should be prioritized as potential etiologic factors for EAO tumorigenesis.
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Affiliation(s)
- Sean G Kraus
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
- McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin–Madison, Madison, WI, USA
| | - Katherine A Johnson
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
- McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin–Madison, Madison, WI, USA
| | - Philip B Emmerich
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
- McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin–Madison, Madison, WI, USA
| | - Linda Clipson
- McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin–Madison, Madison, WI, USA
| | - Cheri A Pasch
- University of Wisconsin Carbone Cancer Center, Madison, WI, USA
| | - Wei Zhang
- University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, Madison, WI, USA
| | - Kristina A Matkowskyj
- University of Wisconsin Carbone Cancer Center, Madison, WI, USA
- Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, Madison, WI, USA
- William S. Middleton Veterans Administration Health System, Madison, WI, USA
| | - Dustin A Deming
- Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, USA
- McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin–Madison, Madison, WI, USA
- University of Wisconsin Carbone Cancer Center, Madison, WI, USA
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Vanguardia MK, Lew C, Nguyen TC, Teoh W, Narasimhan V. Don't take this lying down: an urgent wakeup call: the weight of diet and lifestyle in the young-onset colorectal cancer surge. ANZ J Surg 2025. [PMID: 39891476 DOI: 10.1111/ans.19416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 01/14/2025] [Indexed: 02/03/2025]
Affiliation(s)
- Maria Kristina Vanguardia
- Department of General Surgery, Alfred Health, Melbourne, Victoria, Australia
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Chen Lew
- Department of General Surgery, Alfred Health, Melbourne, Victoria, Australia
| | - Thang Chien Nguyen
- Department of Colorectal Surgery, Monash Health, Dandenong, Victoria, Australia
| | - William Teoh
- Department of Colorectal Surgery, Monash Health, Dandenong, Victoria, Australia
| | - Vignesh Narasimhan
- Department of General Surgery, Alfred Health, Melbourne, Victoria, Australia
- Department of Colorectal Surgery, Monash Health, Dandenong, Victoria, Australia
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Brim H, Reddy CS, Chirumamilla L, Oskrochi G, Deverapalli M, Rashid R, Rashid M, Nair V, Morrison N, Byer D, Thompson T, Yasin B, Johnson D, Snowden A, Mammen P, Carter G, Jolly V, Thompson R, Abdulmoniem R, Karodeh N, Gojela Y, Ahmed A, Saroya S, Gibbs T, Dawodu D, Shayegh N, Ahmed AH, Zahedi I, Aduli F, Kibreab A, Laiyemo AO, Shokrani B, Zafar R, Nembhard C, Carethers JM, Ashktorab H. Trends and Symptoms Among Increasing Proportion of African Americans with Early-Onset Colorectal Cancer over a 60-Year Period. Dig Dis Sci 2025; 70:168-176. [PMID: 39586927 DOI: 10.1007/s10620-024-08739-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 11/05/2024] [Indexed: 11/27/2024]
Abstract
BACKGROUND The proportion of early onset colorectal cancer (EOCRC) is alarming in adults, including in African Americans (AA). AIM To investigate differences between EOCRC compared to late-onset colorectal cancer (LOCRC) among AA patients. METHODS This retrospective study reviewed demographic, clinical presentations, colonoscopy, and pathology reports of patients at Howard University Hospital from 1959 to 2023. The study included 176 EOCRC cases (< 45 years) and 2034 LOCRC cases (> 45 years). RESULTS Both EOCRC and LOCRC groups were predominantly AA (> 80%) with slightly more females (53%) than males. The mean age was 38 years for EOCRC and 66 years for LOCRC cases. EOCRC cases increased as a proportion of total detected CRC cases since 2010 (over 13%) after several decades of just above 6%. Family history of CRC in first degree relatives was higher among EOCRC (15.5% vs.3.4% in LOCRC patients, p < 0.01). Symptoms at presentation were prevalent in both EOCRC (93.8%) and LOCRC (92.6%). EOCRC patients exhibited higher incidence of abdominal pain (23.3% vs. 17.2%, p = 0.05) and changes in bowel habits (24.4% vs. 14%, p < 0.01) compared to LOCRC patients. Other symptoms such as melena, hematochezia, and weight loss were less prevalent in EOCRC patients. Comorbidities like hypertension (HTN), diabetes mellitus (DM), and inflammatory bowel disease (IBD) were less frequent among EOCRC patients. EOCRC was primarily observed in the sigmoid and rectosigmoid regions (p = 0.02). Metastasis at index colonoscopy was more prevalent with EOCRC compared to LOCRC (p = 0.04), with a higher proportion of patients at stage 3 cancer (p < 0.05). Significant differences were noted in the timeline for undergoing surgery after the diagnosis of colorectal cancer, with EOCRC patients taking longer than LOCRC patients (p = 0.03). CONCLUSION Presentation of EOCRC over LOCRC increased proportionally in our cohort since 2010 and is associated with family history, and symptoms such as abdominal pain and change in bowel habits. Likely because of age at presentation, there are less comorbidities among EOCRC patients who predominantly present in the outpatient setting, and more likely diagnosed with advanced stage lesions that are predominantly sigmoid or rectosigmoid. These findings are similar to observations seen in the general population with EOCRC, albeit African American patients have commonly had earlier age presentation of CRC than White American patients.
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Affiliation(s)
- Hassan Brim
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Challa Suryanarayana Reddy
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Lakshmi Chirumamilla
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Gholamreza Oskrochi
- College of Engineering and Technology, American University of the Middle East, Egaila, Kuwait
| | - Mrinalini Deverapalli
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Rumaisa Rashid
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Mudasir Rashid
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Vaisakh Nair
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Nicole Morrison
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Danae Byer
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Trae Thompson
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Belal Yasin
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - David Johnson
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Alicia Snowden
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Priscilla Mammen
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Gabriel Carter
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Victor Jolly
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Rasheed Thompson
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Riad Abdulmoniem
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Nima Karodeh
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Yafiet Gojela
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Ali Ahmed
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Sabtain Saroya
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Trinity Gibbs
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Dideolu Dawodu
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Nader Shayegh
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Ali H Ahmed
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Iman Zahedi
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Farshad Aduli
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Angesom Kibreab
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Adeyinka O Laiyemo
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Babak Shokrani
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Rabia Zafar
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Christine Nembhard
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - John M Carethers
- Department of Medicine, Moores Cancer Center, Wertheim School of Public Health and Human Longevity, University of California San Diego, San Diego, CA, USA
| | - Hassan Ashktorab
- Department of Medicine, Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA.
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Gandini A, Taieb J, Blons H, Netter J, Laurent-Puig P, Gallois C. Early-Onset colorectal Cancer: From the laboratory to the clinic. Cancer Treat Rev 2024; 130:102821. [PMID: 39236404 DOI: 10.1016/j.ctrv.2024.102821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 08/28/2024] [Indexed: 09/07/2024]
Abstract
Colorectal cancer that occurs before age of 50 is defined as Early-Onset Colorectal Cancer (EOCRC). Its incidence has worryingly increased since the late 90 s and is expected to keep rising in the next future, despite Late-Onset CRC (LOCRC) is decreasing worldwide. Because of this, there is an urgent need to better understand this subset of patients in order to give them the best treatment possible. However, most of the literature is retrospective and often discordant. In this review, we aim to provide a general overview of the issue, endeavoring to highlight the current available knowledge. We decided to move from the beginning, investigating risk factors and inheritance, passing through diagnosis and clinical aspects, and to conclude with the translational part, focusing on the biology of the tumor. However, lot of questions remain open, including screening age and prognosis. Indeed, young patients tend to be treated more aggressively, even if a survival benefit has not been proven yet. Every clinician should be aware of the best practice for young people, and more translational studies are awaited in order to clarify is EOCRC represents a distinct biological entity.
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Affiliation(s)
- Annalice Gandini
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, AP-HP Centre, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France
| | - Julien Taieb
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, AP-HP Centre, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France
| | - Hélène Blons
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Assistance Publique-Hôpitaux de Paris, Department of Biochemistry, Pharmacogenetics and Molecular Oncology, European Georges Pompidou Hospital, Paris Cancer Institute CARPEM, 20 Rue Leblanc, 75015, Paris, France; Department of Genetics and Molecular Medicine, Georges Pompidou European Hospital, APHP Centre, Paris, France
| | - Jeanne Netter
- Institut du Cancer Paris CARPEM, AP-HP Centre, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France
| | - Pierre Laurent-Puig
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, APHP. Centre, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France
| | - Claire Gallois
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, AP-HP Centre, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France.
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7
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Güzel HG, Koçer M, Yıldız M, Öztürk B, Kıvrak Salim D, Karaca M. Rectal Cancer in Young Adults: A Single Center Experience. J Adolesc Young Adult Oncol 2024. [PMID: 39419018 DOI: 10.1089/jayao.2024.0090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024] Open
Abstract
Purpose: Individuals below the age of 40 make up only 3%-11% of colorectal cancer (CRC) cases. In this study, we aimed to review clinicopathological characteristics of rectal cancer in young adults. Methods: Rectal adenocancer patients aged ≤40 were included in this study from Antalya Training and Research Hospital. A single-arm descriptive study was designed. Results: There were 85 patients in the final analyses (n = 85). The median age was 37 (19-40). Mucinous adenocarcinoma and signet-cell carcinoma rates were 11.8% for each. Twenty patients (24.4%) had high-grade cancer. Fourteen patients (16.5%) had CRC history in a first-degree relative. None of the patients were diagnosed through a screening test. Of the 85 patients, 41 (48.2%) were stage 3 and 23 (27.1%) were stage 4 at the time of diagnosis. Thirty-four (54.8%) of the 62 nonmetastatic patients had neoadjuvant and 27 (43.5%) had adjuvant treatment because of having an upfront surgery before presentation. In the nonmetastatic population, the 5-year disease-free survival rate was 69.7 ± 6.5%. De-novo metastatic underwent chemotherapy, and biological agents were administered when feasible. KRAS mutation rate was 56.5% among metastatic patients. The median progression-free survival for the first-line treatment was 11.2 months (5.7-16.6), and the median overall survival was 22.3 months (15.4-29.1). Conclusion: We demonstrated that rectal cancer is usually diagnosed at late stages in young individuals which is compatible with the previous reports. Low cancer awareness in young patients and their caregivers and adverse histological features were advocated as the reason for the diagnostic delay. However, future studies may elucidate the reason behind the common diagnosis at advanced stages.
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Affiliation(s)
- Halil Göksel Güzel
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Murat Koçer
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Mustafa Yıldız
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Banu Öztürk
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Derya Kıvrak Salim
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Mustafa Karaca
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya, Turkey
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8
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Pellino G, Fuschillo G, González-Sarmiento R, Martí-Gallostra M, Selvaggi F, Espín-Basany E, Perea J. Risk of metachronous neoplasia in early-onset colorectal cancer: meta-analysis. BJS Open 2024; 8:zrae092. [PMID: 39230922 PMCID: PMC11373379 DOI: 10.1093/bjsopen/zrae092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 07/01/2024] [Accepted: 07/08/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Metachronous colorectal cancer refers to patients developing a second colorectal neoplasia diagnosed at least 6 months after the initial cancer diagnosis, excluding recurrence. The aim of this systematic review is to assess the incidence of metachronous colorectal cancer in early-onset colorectal cancer (defined as age at diagnosis of less than 50 years) and to identify risk factors. METHODS This is a systematic review and meta-analysis performed following the PRISMA statement and registered on PROSPERO. The literature search was conducted in PubMed and Embase. Only studies involving patients with early-onset colorectal cancer (less than 50 years old) providing data on metachronous colorectal cancer were included in the analysis. The primary endpoint was the risk of metachronous colorectal cancer in patients with early-onset colorectal cancer. Secondary endpoints were association with Lynch syndrome, family history and microsatellite instability. RESULTS Sixteen studies met the inclusion criteria. The incidence of metachronous colorectal cancer was 2.6% (95% c.i. 2.287-3.007). The risk of developing metachronous colorectal cancer in early-onset colorectal cancer versus non-early-onset colorectal cancer patients demonstrated an OR of 0.93 (95% c.i. 0.760-1.141). The incidence of metachronous colorectal cancer in patients with Lynch syndrome was 18.43% (95% c.i. 15.396-21.780), and in patients with family history 10.52% (95% c.i. 5.555-17.659). The proportion of metachronous colorectal cancer tumours in the microsatellite instability population was 19.7% (95% c.i. 13.583-27.2422). CONCLUSION The risk of metachronous colorectal cancer in patients with early-onset colorectal cancer is comparable to those with advanced age, but it is higher in patients with Lynch syndrome, family history and microsatellite instability. This meta-analysis demonstrates the need to personalize the management of patients with early-onset colorectal cancer according to their risk factors.
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Affiliation(s)
- Gianluca Pellino
- Colorectal Surgery, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain
| | - Giacomo Fuschillo
- Colorectal Surgery, Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | | | - Marc Martí-Gallostra
- Colorectal Surgery, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain
| | - Francesco Selvaggi
- Colorectal Surgery, Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Eloy Espín-Basany
- Colorectal Surgery, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain
| | - Jose Perea
- Molecular Medicine, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain
- Department of Surgery, Vithas Arturo Soria University Hospital, Madrid, Spain
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Wang Y, Wu ZL, Wang YG, Wang H, Jia XY. Early colorectal cancer screening–no time to lose. World J Gastroenterol 2024; 30:2959-2963. [PMID: 38946873 PMCID: PMC11212702 DOI: 10.3748/wjg.v30.i23.2959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 05/15/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
In this editorial, we comment on the article entitled “Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?” by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.
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Affiliation(s)
- Ying Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 310018, Zhejiang Province, China
| | - Zheng-Long Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Yi-Gang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Hui Wang
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 310018, Zhejiang Province, China
| | - Xiao-Yuan Jia
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
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10
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Jalali A, Smith S, Kim G, Wong H, Lee M, Yeung J, Loft M, Wong R, Shapiro JD, Kosmider S, Tie J, Ananda S, Ma B, Burge M, Jennens R, Lee B, Johns J, Lim L, Dean A, Nott L, Gibbs P. Early onset metastatic colorectal cancer in Australia. Cancer Treat Res Commun 2024; 40:100827. [PMID: 38885543 DOI: 10.1016/j.ctarc.2024.100827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 04/29/2024] [Accepted: 06/11/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.
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Affiliation(s)
- A Jalali
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Northern Health, VIC, Australia; Department of Medical Oncology, Latrobe Regional Hospital, VIC, Australia.
| | - S Smith
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, St Vincent's Hospital Melbourne, VIC, Australia
| | - G Kim
- Department of Medical Oncology, Western Health, VIC, Australia
| | - H Wong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - M Lee
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Eastern Health, VIC, Australia; Eastern Health Clinical School, Monash University, VIC, Australia
| | - J Yeung
- Department of Colorectal Surgery, Western Health, University of Melbourne, VIC, Australia; Department of Surgery, Western Precinct, University of Melbourne, VIC, Australia
| | - M Loft
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - R Wong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Eastern Health Clinical School, Monash University, VIC, Australia; Department of Surgery, Western Precinct, University of Melbourne, VIC, Australia
| | - J D Shapiro
- Department of Medical Oncology, Cabrini Hospital, VIC, Australia
| | - S Kosmider
- Department of Medical Oncology, Western Health, VIC, Australia
| | - J Tie
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - S Ananda
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - B Ma
- The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
| | - M Burge
- Department of Medical Oncology, Royal Brisbane Hospital, QLD, Australia
| | - R Jennens
- Department of Medical Oncology, Epworth Health, VIC, Australia
| | - B Lee
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Northern Health, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - J Johns
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - L Lim
- Department of Medical Oncology, Eastern Health, VIC, Australia
| | - A Dean
- Department of Medical Oncology, St John of God Hospital, WA, Australia
| | - L Nott
- Department of Medical Oncology, Royal Hobart Hospital, TAS, Australia
| | - P Gibbs
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia
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11
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Demb J, Kolb JM, Dounel J, Fritz CDL, Advani SM, Cao Y, Coppernoll-Blach P, Dwyer AJ, Perea J, Heskett KM, Holowatyj AN, Lieu CH, Singh S, Spaander MCW, Vuik FER, Gupta S. Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open 2024; 7:e2413157. [PMID: 38787555 PMCID: PMC11127127 DOI: 10.1001/jamanetworkopen.2024.13157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 03/19/2024] [Indexed: 05/25/2024] Open
Abstract
Importance Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. Objective To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. Data Sources PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. Study Selection Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. Data Extraction and Synthesis Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. Main Outcomes and Measures Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. Results Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). Conclusions and Relevance In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.
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Affiliation(s)
- Joshua Demb
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Jennifer M. Kolb
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, California
| | - Jonathan Dounel
- Department of Medicine, University of California San Diego, La Jolla
| | | | - Shailesh M. Advani
- Department of Internal Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri
| | | | - Andrea J. Dwyer
- University of Colorado Cancer Center, Colorado School of Public Health, Aurora
| | - Jose Perea
- Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, Spain
- Surgery Department, Vithas Arturo Soria University Hospital, Madrid, Spain
| | - Karen M. Heskett
- UC San Diego Library, University of California San Diego, La Jolla
| | - Andreana N. Holowatyj
- Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Christopher H. Lieu
- Division of Medical Oncology, University of Colorado Denver Anschutz Medical Campus, Aurora
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Manon C. W. Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Fanny E. R. Vuik
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Samir Gupta
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
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Torkashvand R, Hajikhani B, Hosseini Doust R, Dabiri H, Dadashi M. Associations Between Fusobacterium nucleatum and msh2, mlh1, and msh6 Gene Expression in Colorectal Cancer. Jundishapur J Microbiol 2024; 17. [DOI: 10.5812/jjm-144247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 01/03/2025] Open
Abstract
Background: Colorectal cancer (CRC) is a major global health concern, and the link with Fusobacterium nucleatum has received considerable attention. Objectives: This study aimed to explore the prevalence of F. nucleatum and to assess the expression of the msh2, mlh1, and msh6 genes in CRC patients compared to a control group using real-time PCR. Methods: Forty CRC patients and twenty individuals from a control group participated in this study. Gastroenterologists collected biopsy specimens from which DNA and RNA were extracted using a specialized tissue extraction kit. Complementary DNA (cDNA) was then synthesized. Real-time PCR was employed to evaluate the expression levels of the msh2, mlh1, and msh6 genes and the presence of the F. nucleatum-specific 16srRNA gene to determine the relative prevalence of this bacterium in each group. Results: Results indicated a higher prevalence of the F. nucleatum-specific 16srRNA gene in CRC patients than in the control group. Additionally, expression levels of the msh2, mlh1, and msh6 genes were significantly higher in the cancer group, suggesting their role in CRC pathogenesis. The distribution of F. nucleatum was particularly high in the sigmoid and rectum areas of the colon. Conclusions: This study underscores the significance of F. nucleatum in CRC and provides insights into its association with altered gene expression patterns. Understanding the prevalence of F. nucleatum and its impact on msh2, mlh1, and msh6 genes may aid in developing improved diagnostic and therapeutic strategies for CRC. Further research is necessary to elucidate these relationships more comprehensively.
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13
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Baronas VA, Arif AA, Bhang E, Ladua GK, Brown CJ, Donnellan F, Gill S, Stuart HC, Loree JM. Symptom Burden and Time from Symptom Onset to Cancer Diagnosis in Patients with Early-Onset Colorectal Cancer: A Multicenter Retrospective Analysis. Curr Oncol 2024; 31:2133-2144. [PMID: 38668061 PMCID: PMC11049268 DOI: 10.3390/curroncol31040158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/21/2024] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
Background: The incidence of colorectal cancer (CRC) is decreasing in individuals >50 years due to organised screening but has increased for younger individuals. We characterized symptoms and their timing before diagnosis in young individuals. Methods: We identified all patients diagnosed with CRC between 1990-2017 in British Columbia, Canada. Individuals <50 years (n = 2544, EoCRC) and a matched cohort >50 (n = 2570, LoCRC) underwent chart review to identify CRC related symptoms at diagnosis and determine time from symptom onset to diagnosis. Results: Across all stages of CRC, EoCRC presented with significantly more symptoms than LoCRC (Stage 1 mean ± SD: 1.3 ± 0.9 vs. 0.7 ± 0.9, p = 0.0008; Stage 4: 3.3 ± 1.5 vs. 2.3 ± 1.7, p < 0.0001). Greater symptom burden at diagnosis was associated with worse survival in both EoCRC (p < 0.0001) and LoCRC (p < 0.0001). When controlling for cancer stage, both age (HR 0.87, 95% CI 0.8-1.0, p = 0.008) and increasing symptom number were independently associated with worse survival in multivariate models. Conclusions: Patients with EoCRC present with a greater number of symptoms of longer duration than LoCRC; however, time from patient reported symptom onset was not associated with worse outcomes.
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Affiliation(s)
- Victoria A. Baronas
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
| | - Arif A. Arif
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
| | - Eric Bhang
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
| | - Gale K. Ladua
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
| | - Carl J. Brown
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
- Department of Surgery, Division of General Surgery, St. Paul’s Hospital, Vancouver, BC V6Z1Y6, Canada
| | - Fergal Donnellan
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
- Division of Gastroenterology, Vancouver General Hospital, Vancouver, BC V5Z1M9, Canada
| | - Sharlene Gill
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
- BC Cancer, Vancouver, BC V6E1Y6, Canada
| | - Heather C. Stuart
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
- BC Cancer, Vancouver, BC V6E1Y6, Canada
| | - Jonathan M. Loree
- Division of Gastroenterology, University of British Columbia, Vancouver, BC V6T1Z4, Canada; (V.A.B.); (A.A.A.); (E.B.); (G.K.L.); (C.J.B.); (F.D.); (S.G.)
- BC Cancer, Vancouver, BC V6E1Y6, Canada
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14
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Lane DS, Smith RA. Cancer Screening: Patient and Population Strategies. Med Clin North Am 2023; 107:989-999. [PMID: 37806730 DOI: 10.1016/j.mcna.2023.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2023]
Abstract
Although cancer has been the second leading cause of death for close to 100 years, progress has been made in reducing cancer mortality and morbidity, with the adoption of high-quality screening tests and treatment advances delivered at earlier stages of diagnosis. To achieve the high cancer screening rates demonstrated by some practices, proven effective strategies need to be broadly adopted at both the patient and population levels. Factors affecting cancer screening test completion and approaches to improvement are described both generally and for breast, lung, cervical, colorectal, and prostate cancers. Closing the racial disparity gap is a critical component of reaching cancer screening and prevention goals.
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Affiliation(s)
- Dorothy S Lane
- Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8222, USA.
| | - Robert A Smith
- Early Cancer Detection Science Department, American Cancer Society
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15
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Park SB, Yoon JY, Kwak MS, Cha JM. Clinical and pathological characteristics of early-onset colorectal cancer in South Korea. Saudi J Gastroenterol 2023; 29:358-364. [PMID: 37470634 PMCID: PMC10754381 DOI: 10.4103/sjg.sjg_35_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 05/30/2023] [Accepted: 06/03/2023] [Indexed: 07/21/2023] Open
Abstract
Background Early-onset colorectal cancer (EOCRC) may differ by race and ethnicity, and recently South Korea has witnessed a surge in cases. We aimed to evaluate the clinical and pathological features of patients with EOCRC, and to determine the predictors of overall survival. Methods In this retrospective study, EOCRC was defined as CRC diagnosed in patients aged < 50 years, and late-onset CRC was defined as CRC diagnosed in those over 75 years of age. The clinical and pathological characteristics of patients with EOCRC were compared with late-onset CRC. We also used multivariable Cox proportional hazard models to find predictors of overall survival in patients with EOCRC. Results The proportion of early-onset CRC was 9.1% of 518 patients with CRC, and the clinical and pathological characteristics were similar between early-onset (n = 47) and late-onset CRC (n = 134). However, EOCRC had a preponderance for distal tumor location (70.2% vs. 50.7%, P = 0.02) and T1-2 stage disease (23.4% vs. 11.2%, P = 0.04), compared with those of late-onset CRC. Using multivariable Cox proportional hazard models, only vascular invasion (hazard ratio = 8.75, 95% confidence interval 1.139‒67.197) was found to be a risk factor for overall survival (P = 0.04) for patients with CRC. Conclusion EOCRC had preponderance for distal tumor location and early T-stage disease, compared with late-onset CRC. Considering the increasing incidence of EOCRC, more studies on clinical and pathological characteristics of EOCRC may be warranted.
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Affiliation(s)
- Su Bee Park
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jin Young Yoon
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Min Seob Kwak
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
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Demb J, Liu L, Murphy CC, Doubeni CA, Martinez ME, Gupta S. Time to Endoscopy or Colonoscopy Among Adults Younger Than 50 Years With Iron-Deficiency Anemia and/or Hematochezia in the VHA. JAMA Netw Open 2023; 6:e2341516. [PMID: 37930701 PMCID: PMC10628727 DOI: 10.1001/jamanetworkopen.2023.41516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 09/24/2023] [Indexed: 11/07/2023] Open
Abstract
Importance To date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized. Objective To evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia. Design, Setting, and Participants This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with a diagnosis of hematochezia (n = 189 185). Statistical analysis was conducted from August 2021 to August 2023. Exposures Diagnostic testing factors included age, sex, race and ethnicity, Veterans Health Administration geographic region, and hemoglobin test value (IDA cohort only). Main Outcomes and Measures Primary outcomes of diagnostic testing were (1) bidirectional endoscopy after diagnosis of IDA and (2) colonoscopy or sigmoidoscopy after diagnosis of hematochezia. The association between diagnostic testing factors and diagnostic test completion was examined using Poisson models. Results There were 59 169 veterans with a diagnosis of IDA (mean [SD] age, 40.7 [7.1] years; 30 502 men [51.6%]), 189 185 veterans with a diagnosis of hematochezia (mean [SD] age, 39.4 [7.6] years; 163 690 men [86.5%]), and 2287 veterans with IDA and hematochezia (mean [SD] age, 41.6 [6.9] years; 1856 men [81.2%]). The cumulative 2-year diagnostic workup completion rate was 22% (95% CI, 22%-22%) among veterans with IDA and 40% (95% CI, 40%-40%) among veterans with hematochezia. Veterans with IDA were mostly aged 40 to 49 years (37 719 [63.7%]) and disproportionately Black (24 480 [41.4%]). Women with IDA (rate ratio [RR], 0.42; 95% CI, 0.40-0.43) had a lower likelihood of diagnostic test completion compared with men with IDA. Black (RR, 0.65; 95% CI, 0.62-0.68) and Hispanic (RR, 0.88; 95% CI, 0.82-0.94) veterans with IDA were less likely to receive diagnostic testing compared with White veterans with IDA. Veterans with hematochezia were mostly White (105 341 [55.7%]). Among veterans with hematochezia, those aged 30 to 49 years were more likely to receive diagnostic testing than adults younger than 30 years of age (age 30-39 years: RR, 1.15; 95% CI, 1.12-1.18; age 40-49 years: RR, 1.36; 95% CI, 1.33-1.40). Hispanic veterans with hematochezia were less likely to receive diagnostic testing compared with White veterans with hematochezia (RR, 0.96; 95% CI, 0.93-0.98). Conclusions and Relevance In the cohorts of veterans younger than 50 years with IDA and/or hematochezia, the diagnostic test completion rate was low. Follow-up was less likely among female, Black, and Hispanic veterans with IDA and Hispanic veterans with hematochezia. Optimizing timely follow-up across social and demographic groups may contribute to improving colorectal cancer outcomes and mitigate disparities.
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Affiliation(s)
- Joshua Demb
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Lin Liu
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
- Moores Cancer Center, University of California, San Diego, La Jolla
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla
| | - Caitlin C. Murphy
- University of Texas Health Science Center at Houston (UTHealth Houston) School of Public Health, Houston
| | - Chyke A. Doubeni
- Department of Family and Community Medicine of the College of Medicine. Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus
| | - Maria Elena Martinez
- Moores Cancer Center, University of California, San Diego, La Jolla
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla
| | - Samir Gupta
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
- Moores Cancer Center, University of California, San Diego, La Jolla
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17
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Lingas EC. Early-Onset Colon Cancer: A Narrative Review of Its Pathogenesis, Clinical Presentation, Treatment, and Prognosis. Cureus 2023; 15:e45404. [PMID: 37854763 PMCID: PMC10579844 DOI: 10.7759/cureus.45404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2023] [Indexed: 10/20/2023] Open
Abstract
Colon cancer remains a leading cause of cancer-related deaths, and there has been a rise in the incidence of early-onset colon cancer or colon cancer diagnosed before the age of 50 years old. Early-onset colon cancer has several differences in clinical presentation, as well as histopathology, genetic alteration, and molecular profiling. Early-onset colon cancer can be differentiated into familial type that includes hereditary familial syndrome and sporadic type. Demographic variance also exists in both developing and developed countries. Due to the rising incidence of colon cancer diagnosed in younger age, it is imperative to examine the available evidence regarding the mortality rate of early-onset colon cancer. Colon cancer is affected by numerous modifiable and non-modifiable risk factors. Increasing obesity and lifestyle disorders in the younger population, such as smoking, may influence this increasing trend. There are existing guidelines for colon cancer screening in both average-risk and high-risk individuals. This narrative review aims to highlight the pathogenesis of early-onset CRC; its clinical presentation, treatment, prognosis; and how it differs from late-onset CRC.
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Affiliation(s)
- Elvina C Lingas
- Hospital Medicine, New York University (NYU) Langone Health Long Island Community Hospital, Patchogue, USA
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18
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Adigun AO, Adebile TM, Okoye C, Ogundipe TI, Ajekigbe OR, Mbaezue RN, Okobi OE. Causes and Prevention of Early-Onset Colorectal Cancer. Cureus 2023; 15:e45095. [PMID: 37842356 PMCID: PMC10569084 DOI: 10.7759/cureus.45095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2023] [Indexed: 10/17/2023] Open
Abstract
Sporadic colorectal cancer (CRC) has historically been considered a disease of the elderly. However, early-onset colorectal cancer (eoCRC) incidence and prevalence have steadily increased over the last few decades, highlighting the critical need for a comprehensive understanding of its causes and prevention. This research examines the numerous factors contributing to the increasing incidence of eoCRC. These factors include a combination of genetic predispositions and environmental effects. We also investigate the impact of modifiable lifestyle factors like obesity, physical inactivity, and an unhealthy diet on eoCRC risk. Understanding these factors is critical in developing future diagnostic, prognostic, disease monitoring, and therapy planning strategies in managing eoCRC and will help optimize guidelines for CRC screening.
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Affiliation(s)
- Aisha O Adigun
- Infectious Diseases, University of Louisville, Louisville, USA
| | - Temitayo M Adebile
- Public Health, Georgia Southern University, Statesboro, USA
- Nephrology, Boston Medical Center, Boston, USA
| | - Chiugo Okoye
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Omolola R Ajekigbe
- Family Medicine, Ladoke Akintola University of Technology, Ogbomoso, NGA
| | | | - Okelue E Okobi
- Family Medicine, Larkin Community Hospital Palm Springs Campus, Hialeah, USA
- Family Medicine, Medficient Health Systems, Laurel, USA
- Family Medicine, Lakeside Medical Center, Belle Glade, USA
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19
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Thompson N, Gatenby G, Waddell O, Purcell R, Keenan J, Pearson JF, Frizelle F, Glyn T. Early onset colorectal cancer in Canterbury, New Zealand. ANZ J Surg 2023; 93:2148-2154. [PMID: 36852900 DOI: 10.1111/ans.18357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/11/2023] [Accepted: 02/17/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND The overall incidence of colorectal cancer is decreasing in much of the world, yet the incidence in those under 50 years of age is increasing (early onset colorectal cancer (EOCRC)). The reasons for this are unclear. This study was undertaken to describe the clinical, pathological and familial characteristics of patients with EOCRC and their oncological outcomes and compare this with previously published data on late onset colorectal cancer (LOCRC). METHODS A retrospective review of all patients diagnosed with EOCRC in Canterbury between 2010 and 2017 was conducted. Data was collected on demographics, family history, treatment, and oncologic outcomes. Kaplan-Meier survival curves were calculated to assess overall survival based on disease stage. RESULTS During the study period (2010-2017) there were 3340 colorectal cancers diagnosed in Canterbury, of which 201 (6%) were in patients under 50 years (range: 17-49). Of these, 87 (43.3%) were female and 125 (62.2%) were aged between 40 and 49 years. 28 (13.9%) were associated with hereditary conditions. Of the 201 patients, 139 (69.2%) had rectal or left-sided cancers. 142 (70.6%) patients presented with either stage 3 or 4 disease and the 5-year overall survival by stage was 79.1% and 14.4%, respectively. CONCLUSION EOCRC is increasing and usually presents as distal left sided cancers, and often at an advanced stage. They do not appear to have the common risk factors of family history or inherited pre-disposition for colorectal cancer. Planning by healthcare providers for this epidemiological change is imperative in investigating symptomatic patients under 50 and optimizing early detection and prevention.
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Affiliation(s)
- Nasya Thompson
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Grace Gatenby
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Oliver Waddell
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Rachel Purcell
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Jacqui Keenan
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - John F Pearson
- Biostatistics and Computational Biology Unit, University of Otago Christchurch, Christchurch, New Zealand
| | - Francis Frizelle
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Tamara Glyn
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
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20
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Martinez-Perez D, Viñal D, Peña-Lopez J, Jimenez-Bou D, Ruiz-Gutierrez I, Martinez-Recio S, Alameda-Guijarro M, Rueda-Lara A, Martin-Montalvo G, Ghanem I, Custodio AB, Trilla-Fuertes L, Gamez-Pozo A, Barbachano A, Rodriguez-Cobos J, Bustamante-Madrid P, Fernandez-Barral A, Burgos A, Prieto-Nieto MI, Pastrian LG, González-Sancho JM, Muñoz A, Feliu J, Rodríguez-Salas N. Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience. Cancers (Basel) 2023; 15:4242. [PMID: 37686518 PMCID: PMC10487095 DOI: 10.3390/cancers15174242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/18/2023] [Accepted: 08/21/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. METHODS We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. RESULTS A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). CONCLUSIONS EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.
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Affiliation(s)
- Daniel Martinez-Perez
- Department of Medical Oncology, Central University Hospital of Asturias, 33011 Oviedo, Spain; (D.M.-P.); (J.F.); (N.R.-S.)
| | - David Viñal
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Jesús Peña-Lopez
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Diego Jimenez-Bou
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Iciar Ruiz-Gutierrez
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Sergio Martinez-Recio
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain;
| | - María Alameda-Guijarro
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Antonio Rueda-Lara
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Gema Martin-Montalvo
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
| | - Ismael Ghanem
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
| | - Ana Belén Custodio
- Department of Medical Oncology, Hospital Universitario La Paz, 28046 Madrid, Spain; (J.P.-L.); (D.J.-B.); (I.R.-G.); (M.A.-G.); (A.R.-L.); (G.M.-M.); (I.G.); (A.B.C.)
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
| | - Lucia Trilla-Fuertes
- Molecular Oncology and Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain; (L.T.-F.); (A.G.-P.)
| | - Angelo Gamez-Pozo
- Molecular Oncology and Pathology Lab, Institute of Medical and Molecular Genetics-INGEMM, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain; (L.T.-F.); (A.G.-P.)
| | - Antonio Barbachano
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
| | - Javier Rodriguez-Cobos
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
| | - Pilar Bustamante-Madrid
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
| | - Asuncion Fernandez-Barral
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
| | - Aurora Burgos
- Department of Gastroenterology, Hospital Universitario La Paz, 28046 Madrid, Spain;
| | - Maria Isabel Prieto-Nieto
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Department of Surgery, Hospital Universitario La Paz, 28046 Madrid, Spain
| | - Laura Guerra Pastrian
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
- Department of Pathology, Hospital Universitario La Paz, 28046 Madrid, Spain
| | - José Manuel González-Sancho
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
| | - Alberto Muñoz
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
| | - Jaime Feliu
- Department of Medical Oncology, Central University Hospital of Asturias, 33011 Oviedo, Spain; (D.M.-P.); (J.F.); (N.R.-S.)
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
- Catedra UAM-AMGEN, 28046 Madrid, Spain
| | - Nuria Rodríguez-Salas
- Department of Medical Oncology, Central University Hospital of Asturias, 33011 Oviedo, Spain; (D.M.-P.); (J.F.); (N.R.-S.)
- Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain; (A.B.); (J.R.-C.); (P.B.-M.); (A.F.-B.); (M.I.P.-N.); (J.M.G.-S.); (A.M.)
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;
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Fritz CDL, Otegbeye EE, Zong X, Demb J, Nickel KB, Olsen MA, Mutch M, Davidson NO, Gupta S, Cao Y. Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. J Natl Cancer Inst 2023; 115:909-916. [PMID: 37138415 PMCID: PMC10407716 DOI: 10.1093/jnci/djad068] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 04/02/2023] [Accepted: 04/14/2023] [Indexed: 05/05/2023] Open
Abstract
BACKGROUND Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise. METHODS We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis. RESULTS Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend < .001), respectively, with stronger associations for younger ages (Pinteraction < .001) and rectal cancer (Pheterogenity = .012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18 months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3 months and 2 years before diagnosis (median diagnostic interval = 8.7 months), and approximately 49.3% had the first sign or symptom within 3 months of diagnosis (median diagnostic interval = 0.53 month). CONCLUSIONS Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.
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Affiliation(s)
- Cassandra D L Fritz
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Ebunoluwa E Otegbeye
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Xiaoyu Zong
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Joshua Demb
- Division of Gastroenterology, University of California San Diego, San Diego, CA, USA
- Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
| | - Katelin B Nickel
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Margaret A Olsen
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Matthew Mutch
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Nicholas O Davidson
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Samir Gupta
- Division of Gastroenterology, University of California San Diego, San Diego, CA, USA
- Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
- Department of Internal Medicine, University of California San Diego, San Diego, CA, USA
- Veteran Affairs San Diego Healthcare System, Department of Medicine, Division of Gastroenterology, San Diego, CA, USA
| | - Yin Cao
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
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Hashmi AA, Aslam M, Rashid K, Ali AH, Dowlah TU, Malik UA, Zia S, Sham S, Zia F, Irfan M. Early-Onset/Young-Onset Colorectal Carcinoma: A Comparative Analysis of Morphological Features and Biomarker Profile. Cureus 2023; 15:e42340. [PMID: 37621838 PMCID: PMC10445772 DOI: 10.7759/cureus.42340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2023] [Indexed: 08/26/2023] Open
Abstract
Introduction Colorectal carcinoma (CRC) is one of the most common cancers that involve the human body. Young-onset CRC (YO-CRC) or early-onset CRC (EO-CRC) is defined as CRC that develops before the age of 50 years, as opposed to CRC that is diagnosed after the age of 50, referred to as late-onset CRC (LO-CRC). EO-CRC is sparsely studied in our population. Therefore, in this study, we evaluated the clinicopathological parameters and biomarker profile of EO-CRC and compared them with those of LO-CRC. Methods This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan. A total of 254 biopsy-proven cases of CRC, reported over a period of nine years, were enrolled in the study. The specimens collected during surgery were sent to the laboratory for histopathological and immunohistochemical (IHC) status examinations. IHC staining of the specimens was performed using antibodies, namely, MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and human epidermal growth factor receptor 2 (HER2/neu), on representative tissue blocks. A comparison of morphological and biomarker profiles between EO-CRC and LO-CRC was performed. Results The mean age at diagnosis was 46.27±17.75 years, with female predominance (59.8%). A significant difference between the two groups (EO-CRC and LO-CRC) was noted with respect to laterality, tumor site, tumor grade, tumor type, presence of pre-existing polyps, perineural invasion (PNI), lymphovascular invasion (LVI), and IHC markers. EO-CRC (as opposed to LO-CRC) significantly affected the left colon (92.6% vs. 72.9%, p<0.001), with the rectosigmoid being the most common site in the majority of cases (72.1% in EO-CRC vs. 61% in LO-CRC). EO-CRC showed a higher frequency of PNI and LVI than LO-CRC (42.6% vs. 23.7%, p=0.001; 29.4% vs. 18.6%, p=0.046, respectively). A significantly higher proportion of EO-CRCs were mucinous (42.6%) and medullary carcinoma (11.8%). Although the majority (54.4%) of cases of EO-CRC were grade 2 tumors at the time of diagnosis, a significantly higher proportion of them were grade 3 (44.1%) compared with LO-CRC. IHC comparisons between the two age groups showed that a significantly higher proportion of cases of EO-CRC showed positive HER2/neu expression (27.1%) compared with LO-CRC (13.2%). Conversely, the loss of expression of microsatellite instability (MSI) markers was more commonly seen in LO-CRS compared with EO-CRC. Conclusions We found a relatively higher frequency of EO-CRC in our population. Moreover, compared with LO-CRCs, EO-CRCs were associated with prognostically poor histological parameters, such as mucinous and medullary carcinoma, high-grade, PNI, and LVI. Similarly, EO-CRC had a higher positive expression of HER2/neu with intact MSI markers compared with AO-CRC; all these characteristics indicate poor biological behavior in EO-CRC.
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Affiliation(s)
- Atif A Hashmi
- Pathology, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Mahnoor Aslam
- Public Health Sciences, University of Alberta, Edmonton, CAN
- Internal Medicine, Baqai Medical University, Karachi, PAK
| | - Khushbakht Rashid
- Internal Medicine, Liaquat National Hospital and Medical College, Karachi, PAK
| | - Abrahim H Ali
- Internal Medicine, Bangladesh Medical College, Dhaka, BGD
| | | | | | - Shamail Zia
- Pathology, Jinnah Sindh Medical University, Karachi, PAK
| | - Sunder Sham
- Pathology, Lenox Hill Hospital, New York, USA
| | - Fazail Zia
- Pathology, Jinnah Sindh Medical University, Karachi, PAK
| | - Muhammad Irfan
- Statistics, Liaquat National Hospital and Medical College, Karachi, PAK
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Moon JY, Kye BH, Ko SH, Yoo RN. Sulfur Metabolism of the Gut Microbiome and Colorectal Cancer: The Threat to the Younger Generation. Nutrients 2023; 15:nu15081966. [PMID: 37111185 PMCID: PMC10146533 DOI: 10.3390/nu15081966] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/13/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Colorectal cancer diagnosed in individuals under 50 years old is called early-onset colorectal cancer (EOCRC), and its incidence has been rising worldwide. Simultaneously occurring with increasing obesity, this worrisome trend is partly explained by the strong influence of dietary elements, particularly fatty, meaty, and sugary food. An animal-based diet, the so-called Western diet, causes a shift in dominant microbiota and their metabolic activity, which may disrupt the homeostasis of hydrogen sulfide concentration. Bacterial sulfur metabolism is recognized as a critical mechanism of EOCRC pathogenesis. This review evaluates the pathophysiology of how a diet-associated shift in gut microbiota, so-called the microbial sulfur diet, provokes injuries and inflammation to the colonic mucosa and contributes to the development of CRC.
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Affiliation(s)
- Ji-Yeon Moon
- Division of Colorectal Surgery, Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| | - Bong-Hyeon Kye
- Division of Colorectal Surgery, Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| | - Ri Na Yoo
- Division of Colorectal Surgery, Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 442-723, Republic of Korea
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24
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Abstract
BACKGROUND Early-onset colorectal cancers are increasing in incidence. Studies reported more left-sided cancers in patients aged <50 years. Some advocate for screening via flexible sigmoidoscopy at age 40 years. OBJECTIVE The purpose of this study was to investigate characteristics and outcomes in sporadic right- and left-sided early-onset colorectal cancers. DESIGN This was a retrospective cohort study. SETTINGS This study was conducted at a single, tertiary care institution. PATIENTS This study included patients aged <50 years diagnosed with colorectal cancer between 2000 and 2018. MAIN OUTCOME MEASURES We analyzed patient demographics, tumor characteristics, and survival. RESULTS A total of 489 patients aged 20 to 49 years were identified from 2000 to 2018. The majority of patients were white (90%) and male (57%). The median age at diagnosis was 44 years, and 75% were diagnosed at age 40-49 years. There was a predominance of left-sided tumors (80%). The majority of patients presented with stage 3 (35%) and stage 4 (35%) disease. Right-sided tumors were more likely to have mucinous (24% vs 7.4%; p < 0.001) and signet-ring cell (4.4% vs 1.7%; p < 0.001) histology. There was no difference in age, sex, race, ethnicity, and stage at presentation. Right-sided tumors were associated with lower 5-year overall survival (44% vs 61%; p < 0.005) with the decrease in survival most prominent in right-sided stage 3 tumors (41% vs 72%; p < 0.0001) and in ages 40 to 49 years (43% vs 61%; p = 0.03). Sex, tumor location, increasing stage, and signet-ring cell histology were independent prognostic factors of overall survival. There was no difference in disease-free survival. LIMITATIONS This study was a retrospective review at a single institution. CONCLUSIONS The majority of early-onset colorectal cancers arise from age 40 to 49 years with a left-sided predominance but higher mortality in right-sided tumors. These findings provide further evidence in favor of recommending earlier initial screening colonoscopy for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B892 . CARACTERSTICAS Y RESULTADOS DEL CNCER COLORRECTAL DE INICIO TEMPRANO DEL LADO DERECHO FRENTE AL IZQUIERDO ANTECEDENTES:Los cánceres colorrectales de aparición temprana están aumentando en incidencia. Los estudios han informado una preponderancia de cánceres en el lado izquierdo en pacientes <50 años, lo que ha llevado a algunos a abogar por la detección con sigmoidoscopia flexible a los 40 años.OBJETIVO:El propósito de nuestro estudio fue investigar las características del tumor y los resultados de los pacientes en cánceres colorrectales esporádicos del lado derecho e izquierdo de aparición temprana.DISEÑO:Este fue un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Este estudio se realizó en una única institución de atención terciaria.PACIENTES:Pacientes <50 años diagnosticados de cáncer colorrectal entre 2000 y 2018.RESULTADO PRINCIPAL:Analizamos los datos demográficos de los pacientes, las características del tumor, la supervivencia general y la supervivencia libre de enfermedad.RESULTADOS:Se identificaron un total de 489 pacientes de entre 20 y 49 años entre 2000 y 2018. La mayoría de los pacientes eran blancos (90%) y varones (57%). La mediana de edad en el momento del diagnóstico fue de 44 años y el 75% se diagnosticó entre los 40 y los 49 años. Predominó los tumores del lado izquierdo (80%). La mayoría de los pacientes presentaban enfermedad en estadio 3 (35%) y estadio 4 (35%). Los tumores del lado derecho tenían más probabilidades de tener histología mucinosa (24% frente a 7,4%, p < 0,001) y de células en anillo de sello (4,4% frente a 1,7%, p < 0,001). No hubo diferencia en edad, sexo, raza, etnia, estadio AJCC en la presentación. Los tumores del lado derecho se asociaron con una menor supervivencia general a 5 años (44% frente al 61%, p < 0,005) con la disminución de la supervivencia más prominente en los tumores del lado derecho en estadio 3 (41% frente al 72%, p < 0,0001) y en edades 40-49 (43% vs 61%, p = 0.03). El sexo, la ubicación del tumor, el estadio AJCC en aumento y la histología de las células en anillo de sello fueron factores pronósticos independientes de la supervivencia general. No hubo diferencias significativas en la supervivencia libre de enfermedad.LIMITACIONES:Este estudio fue una revisión retrospectiva en una sola institución.CONCLUSIONES:La mayoría de los cánceres colorrectales de aparición temprana surgen entre los 40 y los 49 años con un predominio en el lado izquierdo pero una mayor mortalidad en los tumores del lado derecho. Estos hallazgos proporcionan evidencia adicional a favor de recomendar una colonoscopia de detección inicial más temprana para el cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B892 . (Traducción-Dr. Ingrid Melo ).
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25
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Saraiva MR, Rosa I, Claro I. Early-onset colorectal cancer: A review of current knowledge. World J Gastroenterol 2023; 29:1289-1303. [PMID: 36925459 PMCID: PMC10011966 DOI: 10.3748/wjg.v29.i8.1289] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 12/18/2022] [Accepted: 02/15/2023] [Indexed: 02/28/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Although most prevalent among older people, its incidence above 50 years old has been decreasing globally in the last decades, probably as a result of better screening. Paradoxically, its incidence in patients below 50 years old [early-onset CRC (EO-CRC)] has been increasing, for reasons not yet fully understood. EO-CRC's increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide. It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors. Its incidence is predicted to double until 2030, which makes EO-CRC a serious public health issue. Both modifiable and non-modifiable risk factors have been identified - some are potential targets for preventive measures. EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described. EO-CRC presents some distinctive features: Microsatellite in-stability is common, but another subtype of tumours, both microsatellite and chromosome stable also seems relevant. There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data. Due to the higher germline pathological mutations found in EO-CRC patients, an accurate genetic risk evaluation should be performed. In this review, we summarize the current evidence on epidemiological, clinical, histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors. We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.
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Affiliation(s)
- Margarida R Saraiva
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa 1099-023, Portugal
| | - Isadora Rosa
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa 1099-023, Portugal
| | - Isabel Claro
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa 1099-023, Portugal
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Early Onset Colorectal Cancer in Arabs, Are We Dealing with a Distinct Disease? Cancers (Basel) 2023; 15:cancers15030889. [PMID: 36765846 PMCID: PMC9913248 DOI: 10.3390/cancers15030889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 01/23/2023] [Accepted: 01/26/2023] [Indexed: 02/05/2023] Open
Abstract
Early-onset colorectal cancer (EOCRC) incidence is increasing worldwide. Efforts are directed to understand the biological and clinical signatures of EOCRC compared to late-onset colorectal cancer (LOCRC). EOCRC is thought to present differently across different ethnic groups and geographical regions. This study was an attempt to contribute with data from the Arab world toward the understanding of the clinicopathological parameters of EOCRC compared to LOCRC. Data from 254 CRC patients diagnosed at Sultan Qaboos University Hospital from the period 2015-2020 were studied. About 32.6% of all diagnosed CRC patients are below 50 years old, with no differences in gender distribution between EOCRC and LOCRC (p-value 0.417). Rectal involvement and tumor laterality were comparable among the two groups. Adenocarcinoma accounts for 83.3% and 94.2% of EOCRC and LOCRC, respectively. More mucinous and signet ring adenocarcinoma (8.3% each) were reported in EOCRC than LOCRC (2.9% and 2.2%, respectively). MLH1 and PMS2 loss are more common among LOCRC, but MSH6 loss is more frequent in EOCRC. The overall survival of EOCRC and LOCRC was comparable (median survival 64.88 and 67.24 months, respectively). This study showed comparable clinicopathological parameters between EOCRC and LOCRC from Arabs, which adds to the bigger picture of understand the disease.
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27
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Qiu B, Su XH, Qin X, Wang Q. Application of machine learning techniques in real-world research to predict the risk of liver metastasis in rectal cancer. Front Oncol 2022; 12:1065468. [PMID: 36605425 PMCID: PMC9807609 DOI: 10.3389/fonc.2022.1065468] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Background The liver is the most common site of distant metastasis in rectal cancer, and liver metastasis dramatically affects the treatment strategy of patients. This study aimed to develop and validate a clinical prediction model based on machine learning algorithms to predict the risk of liver metastasis in patients with rectal cancer. Methods We integrated two rectal cancer cohorts from Surveillance, Epidemiology, and End Results (SEER) and Chinese multicenter hospitals from 2010-2017. We also built and validated liver metastasis prediction models for rectal cancer using six machine learning algorithms, including random forest (RF), light gradient boosting (LGBM), extreme gradient boosting (XGB), multilayer perceptron (MLP), logistic regression (LR), and K-nearest neighbor (KNN). The models were evaluated by combining several metrics, such as the area under the curve (AUC), accuracy score, sensitivity, specificity and F1 score. Finally, we created a network calculator using the best model. Results The study cohort consisted of 19,958 patients from the SEER database and 924 patients from two hospitals in China. The AUC values of the six prediction models ranged from 0.70 to 0.95. The XGB model showed the best predictive power, with the following metrics assessed in the internal test set: AUC (0.918), accuracy (0.884), sensitivity (0.721), and specificity (0.787). The XGB model was assessed in the outer test set with the following metrics: AUC (0.926), accuracy (0.919), sensitivity (0.740), and specificity (0.765). The XGB algorithm also shows a good fit on the calibration decision curves for both the internal test set and the external validation set. Finally, we constructed an online web calculator using the XGB model to help generalize the model and to assist physicians in their decision-making better. Conclusion We successfully developed an XGB-based machine learning model to predict liver metastasis from rectal cancer, which was also validated with a real-world dataset. Finally, we developed a web-based predictor to guide clinical diagnosis and treatment strategies better.
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Affiliation(s)
- Binxu Qiu
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Xiao hu Su
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Xinxin Qin
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Quan Wang
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
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28
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Ugai T, Sasamoto N, Lee HY, Ando M, Song M, Tamimi RM, Kawachi I, Campbell PT, Giovannucci EL, Weiderpass E, Rebbeck TR, Ogino S. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022; 19:656-673. [PMID: 36068272 PMCID: PMC9509459 DOI: 10.1038/s41571-022-00672-8] [Citation(s) in RCA: 221] [Impact Index Per Article: 73.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2022] [Indexed: 02/07/2023]
Abstract
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased use of screening programmes has contributed to this phenomenon to a certain extent, although a genuine increase in the incidence of early-onset forms of several cancer types also seems to have emerged. Evidence suggests an aetiological role of risk factor exposures in early life and young adulthood. Since the mid-20th century, substantial multigenerational changes in the exposome have occurred (including changes in diet, lifestyle, obesity, environment and the microbiome, all of which might interact with genomic and/or genetic susceptibilities). However, the effects of individual exposures remain largely unknown. To study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data collection technologies. Raising awareness among both the public and health-care professionals will also be critical. In this Review, we describe changes in the incidence of early-onset cancers globally and suggest measures that are likely to reduce the burden of cancers and other chronic non-communicable diseases.
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Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA
| | - Hwa-Young Lee
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Institute of Convergence Science, Convergence Science Academy, Yonsei University, Seoul, Republic of Korea
| | - Mariko Ando
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
| | - Ichiro Kawachi
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Timothy R Rebbeck
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA
- Zhu Family Center for Global Cancer Prevention, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
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29
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Hashmi SSH, Shady A, Atallah-Vinograd J, Cummings D, Maranino A, Harley J. Young-Onset Colon Cancer: A Case Report. Cureus 2022; 14:e29667. [PMID: 36320989 PMCID: PMC9613351 DOI: 10.7759/cureus.29667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2022] [Indexed: 11/17/2022] Open
Abstract
Colorectal cancer (CRC) which is diagnosed in patients under the age of 50 years is defined as young-onset CRC. There has been a substantial increase in the incidence and mortality of young-onset CRC in the past four decades and the patients have delayed diagnoses leading to the advanced stages of CRC at the time of diagnosis. Here we present a case of a 34-year-old male patient with colon cancer and a literature review on young-onset colon cancer to highlight the age-related disparities in CRC incidence and try to explore the possible causative factors for the rise in incidence and mortality in young patients due to CRC.
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30
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Hajipour M, Mokhtari K, Mahdevar M, Esmaeili M, Peymani M, Nasr-Esfahani MH, Mirzaei S, Hasehmi M, Hushmandi K, Ghaedi K. Identification of a novel interplaying loop of PPARγ and respective lncRNAs are involved in colorectal cancer progress. Int J Biol Macromol 2022; 219:779-787. [PMID: 35940433 DOI: 10.1016/j.ijbiomac.2022.07.247] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/24/2022] [Accepted: 07/26/2022] [Indexed: 12/14/2022]
Abstract
Long noncoding RNAs (lncRNAs) as regulatory molecules play important roles in early treatment and diagnosis of cancers. Considering the role of PPARγ in colorectal cancer (CRC) as a tumor suppressor, the GEO database was used to identify candidate genes that affect the activation of PPARγ protein in CRC cell lines. Then were selected 5 genes containing PPARγ response element (PPRE) in up to 4000 bp upstream and were affected by PPARγ protein activation in HT-29 colon cancer cell line using UCSC database. Expression meta-analysis was applied to map the expression network between candidate genes and all known lncRNAs through expression correlation and lncRNAs that correlated with a greater number of candidate genes (R > 0.5, P.value < 0.001). Moreover, were selected 3 lncRNAs as lncRNAs affected by PPARγ protein activation. Next, the expression levels of candidate genes and lncRNAs were evaluated using RT-qPCR in HT-29 cell line. Results showed a significant increase (FDR <0.05) in the expression level of 5 candidate genes and lncRNAs LINC01133, MBNL1-AS, LOC100288911 after treatment with pioglitazone as PPARγ ligand compared to the untreated group in HT-29 cells. Although additional tests are needed to confirm bioinformatics predictions, it can be concluded that increased expression of PPARγ may increase genes and lncRNAs expression. In summary, this study could be suggested identifying lncRNAs affected by PPARγ activation could be a new strategy in understanding the function and activity of PPARγ in colon cancer.
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Affiliation(s)
- Maral Hajipour
- Department of Modern Biology, ACECR Institute of Higher Education (Isfahan Branch), Isfahan, Iran; Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Khatereh Mokhtari
- Department of Modern Biology, ACECR Institute of Higher Education (Isfahan Branch), Isfahan, Iran; Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mohammad Mahdevar
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Maryam Esmaeili
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Maryam Peymani
- Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
| | - Mohammad Hossein Nasr-Esfahani
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mehrdad Hasehmi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
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Abstract
Contrary to decreasing incidence rate of colorectal cancer (CRC) in older adults, incidence rates have nearly doubled in younger adults (age <50 years) in the United States since the early 1990s. A similar increase has been observed across the globe. Despite overall population trends in aging, about 15% of CRCs will be diagnosed in younger adults by 2030. The mechanisms and factors contributing to early-onset CRC (EOCRC) remain puzzling, especially because most young adults diagnosed with CRC have no known risk factors or predisposing conditions, such as family history of CRC or polyps or a hereditary syndrome (eg, Lynch syndrome, polyposis). In this up-to-date review, we discuss the current knowledge of EOCRC, including epidemiology, risk factors, clinical and molecular features, treatment and survival, and recognition and screening strategies.
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Affiliation(s)
- Pooja Dharwadkar
- Division of Gastroenterology, Department of Medicine, University of California San Francisco, Zuckerberg San Francisco General, Building 5, 3rd Floor, Suite 3D, 1001 Potrero Avenue, San Francisco, CA 94110, USA
| | - Timothy A Zaki
- Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
| | - Caitlin C Murphy
- UTHealth School of Public Health, Suite 2618, 7000 Fannin Street, Houston, TX 77030, USA.
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Abstract
Colorectal cancer is the second leading cause of cancer-associated mortality, with a lifetime risk of approximately 4% to 5%. Colorectal cancer develops from the sequential acquisition of defined genetic mutations in the colonic epithelium. Tumorigenesis from normal tissue to cancer occurs largely through 3 pathways: the chromosomal instability pathway, the microsatellite instability pathway, and the sessile serrated pathway. Colorectal cancer incidence and mortality have decreased by approximately 35% since the beginning of screening programs in the 1990s, although other factors such as use of aspirin for coronary disease prevention and decreased smoking rates may also be important. In this review, we discuss the etiology, epidemiology, and histology of colorectal polyps and cancer.
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Nfonsam V, Wusterbarth E, Gong A, Vij P. Early-Onset Colorectal Cancer. Surg Oncol Clin N Am 2022; 31:143-155. [PMID: 35351270 DOI: 10.1016/j.soc.2021.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Venugopal A, Carethers JM. Epidemiology and biology of early onset colorectal cancer. EXCLI JOURNAL 2022; 21:162-182. [PMID: 35221839 PMCID: PMC8859644 DOI: 10.17179/excli2021-4456] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 12/13/2021] [Indexed: 12/14/2022]
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in men or women in the United States. Average-risk screening that begins at age 50 years has reduced incidence and mortality of CRC in those over 50 years of age, whereas CRC incidence in those under age 50 years (early onset colorectal cancer (eoCRC)) has recently and dramatically increased. In this review, we summarize the recent literature including risk factors for eoCRC, differences in clinicopathologic presentation and outcomes in eoCRC, and emerging evidence regarding the molecular pathways that are altered in eoCRC compared to later onset CRC (loCRC). Epidemiologic studies of eoCRC show predominance in distal colon and rectum, and association with several modifiable risk factors, including diabetes, obesity, diet, sedentary time, alcohol consumption and smoking. Data regarding potential risk factors of prior antibiotic exposure and microbiome alterations or direct carcinogen exposure are still emerging. Aggressive clinicopathologic features of eoCRC at presentation may be due to delay in diagnosis or more aggressive tumor biology. EoCRC outcomes are similar to loCRC when matched for stage, but overall mortality is greater due to higher frequency of advanced disease at a younger presentation, with more life-years lost. There are only few molecular evaluations of eoCRC to date, with findings of potential increase in TP53 and CTNNB1 somatic mutation and decrease in APC, KRAS and BRAF somatic mutation, compared to loCRC. Other findings include LINE-1 hypomethylation, absence of microsatellite instability (MSI-H), presence of chromosomal instability (CIN) or microsatellite and chromosomal stability (MACS). These studies are only now emerging and have not yet identified a specific molecular signature defining eoCRC. Further research evaluating genetic and molecular differences as well as environmental triggers for eoCRCs should provide a clearer understanding to inform targeted screening for pre-symptomatic at-risk younger individuals.
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Affiliation(s)
- Anand Venugopal
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - John M Carethers
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.,Department of Human Genetics and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
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Gu J, Li Y, Yu J, Hu M, Ji Y, Li L, Hu C, Wei G, Huo J. A risk scoring system to predict the individual incidence of early-onset colorectal cancer. BMC Cancer 2022; 22:122. [PMID: 35093005 PMCID: PMC8801093 DOI: 10.1186/s12885-022-09238-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 01/20/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND The incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies. METHODS Risk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman-Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations. RESULTS A total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman-Keller model. CONCLUSION This model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.
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Affiliation(s)
- Jialin Gu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China
| | - Yan Li
- Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China
| | - Jialin Yu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Miao Hu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China
| | - Yi Ji
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Lingchang Li
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Canhong Hu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Guoli Wei
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China.
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China.
- Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, Jiangsu, China.
- Yangzhou University Medical College, Yangzhou, 225000, Jiangsu, China.
| | - Jiege Huo
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China.
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China.
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Hoseini B, Rahmatinejad Z, Goshayeshi L, Bergquist R, Golabpour A, Ghaffarzadegan K, Rahmatinejad F, Darrudi R, Eslami S. Colorectal Cancer in North-Eastern Iran: a retrospective, comparative study of early-onset and late-onset cases based on data from the Iranian hereditary colorectal cancer registry. BMC Cancer 2022; 22:48. [PMID: 34998373 PMCID: PMC8742430 DOI: 10.1186/s12885-021-09132-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 12/21/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. METHODS This retrospective study, carried out over a three-year follow-up period (2014-2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years. RESULTS From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS. CONCLUSION The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.
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Affiliation(s)
- Benyamin Hoseini
- Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Rahmatinejad
- Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ladan Goshayeshi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Robert Bergquist
- Formerly UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland
- Ingerod, SE-454 94, Brastad, Sweden
| | - Amin Golabpour
- School of Paramedical , Shahroud University of Medical Sciences, Shahroud, Iran
| | - Kamran Ghaffarzadegan
- Pathology Department, Education and Research Department, Razavi Hospital, Mashhad, Iran
| | - Fatemeh Rahmatinejad
- Department of Health Information Technology, Faculty of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Darrudi
- Department of Health Information Technology, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Saeid Eslami
- Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
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Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol 2022; 7:262-274. [DOI: 10.1016/s2468-1253(21)00426-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 10/27/2021] [Accepted: 11/01/2021] [Indexed: 02/07/2023]
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Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol 2022; 117:57-69. [PMID: 34962727 DOI: 10.14309/ajg.0000000000001548] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 06/15/2021] [Indexed: 12/11/2022]
Abstract
This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.
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39
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Pruthi DS, Nagpal P, Yadav A, Bansal B, Pandey M, Agarwal N. Shifting Paradigm of Adult Cancers at Young Age –A Case Series. CLINICAL CANCER INVESTIGATION JOURNAL 2022. [DOI: 10.51847/wxhwcy0kxx] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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40
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Patel SG, May FP, Anderson JC, Burke CA, Dominitz JA, Gross SA, Jacobson BC, Shaukat A, Robertson DJ. Updates on Age to Start and Stop Colorectal Cancer Screening: Recommendations From the U.S. Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2022; 162:285-299. [PMID: 34794816 DOI: 10.1053/j.gastro.2021.10.007] [Citation(s) in RCA: 119] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 06/15/2021] [Indexed: 02/07/2023]
Abstract
This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.
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Affiliation(s)
- Swati G Patel
- University of Colorado Anschutz Medical Center, Aurora, Colorado; Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado.
| | - Folasade P May
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Vatche and Tamar Manoukian Division of Digestive Diseases and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Joseph C Anderson
- VA Medical Center, White River Junction, Vermont, and the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; University of Connecticut School of Medicine, Farmington, Connecticut
| | | | - Jason A Dominitz
- VA Puget Sound Health Care System and the University of Washington, Seattle, Washington
| | | | | | - Aasma Shaukat
- GI Section, Minneapolis VA Medical Center and University of Minnesota, Minneapolis, Minnesota
| | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont, and the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
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41
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Patel SG, May FP, Anderson JC, Burke CA, Dominitz JA, Gross SA, Jacobson BC, Shaukat A, Robertson DJ. Updates on age to start and stop colorectal cancer screening: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2022; 95:1-15. [PMID: 34794803 DOI: 10.1016/j.gie.2021.06.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 06/15/2021] [Indexed: 02/07/2023]
Abstract
This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals ages 76 to 85, the decision to start or continue screening should be individualized and based on prior screening history, life expectancy, CRC risk, and personal preference. Screening is not recommended after age 85.
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Affiliation(s)
- Swati G Patel
- University of Colorado Anschutz Medical Center, Aurora, Colorado, USA; Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA
| | - Folasade P May
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA; Vatche and Tamar Manoukian Division of Digestive Diseases and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Joseph C Anderson
- VA Medical Center, White River Junction, Vermont, USA and the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA; University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | | | - Jason A Dominitz
- VA Puget Sound Health Care System and the University of Washington, Seattle, Washington, USA
| | | | | | - Aasma Shaukat
- GI Section, Minneapolis VA Medical Center and University of Minnesota, Minneapolis, Minnesota, USA
| | - Douglas J Robertson
- VA Medical Center, White River Junction, Vermont, USA and the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
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McClelland PHT, Liu T, Ozuner G. Early-Onset Colorectal Cancer in Patients under 50 Years of Age: Demographics, Disease Characteristics, and Survival. Clin Colorectal Cancer 2021; 21:e135-e144. [PMID: 34972664 DOI: 10.1016/j.clcc.2021.11.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 10/05/2021] [Accepted: 11/22/2021] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Incidence of early-onset colorectal cancer (EO-CRC) is increasing in younger demographics. This study analyzes disease-specific survival in individuals under 50 years of age. METHODS Patients with colorectal malignancy were identified in the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2015. Cases were categorized into typically screened (age 50-79 years) and non-typically screened (age 20-49 years) cohorts, as well as by decade. Kaplan-Meier curves and Cox proportional hazard models were used to study survival. RESULTS A total of 240,772 patients with colorectal cancer were analyzed. Average annual percent change in incidence was -0.24% among typically screened patients and +1.12% among patients with EO-CRC. Patients with EO-CRC more frequently presented with distal tumors (70.6% vs. 57.6%, P < .001) and advanced tumor stage (61.3% vs. 48.6%, P < .001). Patients aged 50 and over had comparable 5 year disease-specific survival to younger patients (68.2% vs. 66.4%, P = .31); however, patients in the 3rd, 4th, and 8th decade of life had particularly low survival rates (59.0% vs. 65.8% vs. 65.8%, logrank P < .001). Patients aged 20-29 years had the most increased risk of cause-specific mortality on univariable Cox regression analysis [HR 1.43, 95% CI 1.31-1.56; P < .001], although this was not significant on multivariable analysis [HR 1.06, 95% CI 0.97-1.15; P = .201]. Male sex, older age, advanced stage, rectal and/or cecal primary, and earlier year of diagnosis were independently associated with increased mortality. CONCLUSION Patients with EO-CRC are diagnosed at a later stage and have lower disease-specific survival than those in typically screened cohorts. Additional studies on tumor biology and surveillance strategies are needed to improve outcomes in this population.
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Affiliation(s)
| | - Tianming Liu
- Department of Surgery, Baylor College of Medicine, Houston, TX
| | - Gokhan Ozuner
- Department of Surgery, Hackensack Meridian Health, North Bergen, NJ
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Wusterbarth E, Chen Y, Jecius H, Krall E, Runyan RB, Pandey R, Nfonsam V. Cartilage Oligomeric Matrix Protein, COMP may be a Better Prognostic Marker Than CEACAM5 and Correlates With Colon Cancer Molecular Subtypes, Tumor Aggressiveness and Overall Survival. J Surg Res 2021; 270:169-177. [PMID: 34687957 DOI: 10.1016/j.jss.2021.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 08/30/2021] [Accepted: 09/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND New tumor biomarkers are needed to improve the management of Colon cancer (CC), the second leading cause of cancer-related deaths in the United States. Carcinoembryonic Antigen (CEA), the translated protein of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) gene, is used as a biomarker for CC. Cartilage Oligomeric Matrix Protein (COMP) is overexpressed in CC compared to normal colon tissues. This study aims to evaluate the expression of COMP by disease stage, consensus molecular subtype (CMS), its impact on disease outcomes, and comparison to CEACAM5. MATERIALS AND METHODS RNA-seq data from 456 CC The Cancer Genome Atlas samples and 41 matching control samples were analyzed for COMP expression and CEACAM5 expression. We stratified tumor samples by stage (I-IV), subtype (CMS1-CMS4), tumor location, and Kirsten RAt Sarcoma (KRAS) mutant status and three quartiles were established based on COMP expression. Kaplan Meier survival outcomes were evaluated. RESULTS COMP expression was significantly higher in tumor samples, with elevation of expression occurring in stage I and significantly increasing in stage IV. Increased COMP expression occurs in CMS4 with relatively low expression in CMS3. No significant expression difference was attributed to tumor location and KRAS mutant status. Compared to CEACAM5, COMP was a stronger molecular marker across stages and subtypes. CMS4 was associated with the high COMP expression, and higher levels of COMP were associated with poorer overall survival, disease-specific survival, and tumor progression-free intervals. CMS2 and 3 were associated with low expression and better survival. CONCLUSION COMP is a potential molecular biomarker for CC and may be superior to CEA as an indicator of CC.
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Affiliation(s)
- Emily Wusterbarth
- Department of Surgery, University of Arizona Medical Center, Tucson, Arizona
| | - Yuliang Chen
- University of Arizona Cancer Center, Tucson, Arizona
| | - Hunter Jecius
- Department of Surgery, University of Arizona Medical Center, Tucson, Arizona
| | - Erika Krall
- Department of Surgery, University of Arizona Medical Center, Tucson, Arizona
| | - Raymond B Runyan
- Department of Cellular and Molecular Medicine, University of Arizona Medical Center, Tucson, Arizona
| | - Ritu Pandey
- University of Arizona Cancer Center, Tucson, Arizona; Department of Cellular and Molecular Medicine, University of Arizona Medical Center, Tucson, Arizona
| | - Valentine Nfonsam
- Department of Surgery, University of Arizona Medical Center, Tucson, Arizona.
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Wang T, Tsang T, Turshudzhyan A, Dacus H, Tadros M. Updates, Controversies, and Emerging Approaches in Colorectal Screening. Cureus 2021; 13:e17844. [PMID: 34660050 PMCID: PMC8501747 DOI: 10.7759/cureus.17844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/08/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Despite the threatening statistics, the US burden for CRC has been decreasing, which is likely multifactorial and has partial contribution from widespread timely screening, more advanced CRC treatment, and daily aspirin use in some patients. While overall death rate from CRC decreased by approximately a half between 1975 and 2012, epidemiologic studies demonstrate that CRC incidence is increasing in the younger population. This pattern has prompted the American Cancer Society (ACS) to revise their guidelines. In this review, we plan to discuss the most recent changes in guidelines, data to support them, controversies concerning CRC screening methods, age to start and to stop screening, and post-colonoscopy/polypectomy surveillance guidelines.
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Affiliation(s)
- Tiffany Wang
- Internal Medicine, Albany Medical College, Albany, USA
| | - Tyler Tsang
- Internal Medicine, Albany Medical College, Albany, USA
| | | | - Heather Dacus
- Internal Medicine, New York State Department of Health, New York, USA
| | - Micheal Tadros
- Gastroenterology and Hepatology, Albany Medical Center, Albany, USA
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45
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D'Souza N, Monahan K, Benton SC, Wilde L, Abulafi M. Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients. Colorectal Dis 2021; 23:2539-2549. [PMID: 34240526 DOI: 10.1111/codi.15786] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 05/23/2021] [Accepted: 05/31/2021] [Indexed: 12/17/2022]
Abstract
AIM Detection of early onset colorectal cancer is challenging, and remains a rare diagnosis amongst younger people with gastrointestinal symptoms. We investigated whether faecal immunochemical testing (FIT) could identify younger patients at higher risk of colorectal cancer or serious bowel disease including colorectal cancer, inflammatory bowel disease or advanced adenomas. METHODS A subgroup analysis was performed of symptomatic patients under 50 years of age (<50) from the NICE FIT study, a multicentre, prospective diagnostic accuracy study of FIT conducted between October 2017 and December 2019. The diagnostic accuracy of FIT for colorectal cancer and serious bowel disease was investigated in younger patients at different faecal haemoglobin (f-Hb) cut-offs of 2, 10 and 150 µg blood/g faeces (µg/g). RESULTS Early onset colorectal cancer was diagnosed in 1.5% (16/1103) of younger symptomatic patients. The sensitivity of FIT for younger patients aged <50 was 87.5% (95% CI 61.7%-98.4%), 81.3% (54.4%-96.0%) and 68.8% (41.3%-89.0%) at f-Hb cut-offs of 2, 10 and 150 µg/g, respectively. The positive predictive value for colorectal cancer increased from 4.2% (2.3%-6.9%) to 11.5% (5.9%-19.6%) at cut-offs of 2 and 150 µg/g, while the positive predictive value for serious bowel disease increased from 31.3% (26.3%-36.5%) to 65.6% (55.2%-75.0%) at the same cut-offs. The negative predictive value of FIT for colorectal cancer remained above 99.5% at all cut-offs. CONCLUSION Detectable f-Hb on FIT in symptomatic younger patients may indicate referral for investigation of colorectal cancer and serious bowel disease.
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Affiliation(s)
- Nigel D'Souza
- Croydon University Hospital, Croydon, UK.,University Hospital Southampton, Southampton, UK.,Imperial College London, London, UK
| | - Kevin Monahan
- Imperial College London, London, UK.,St Mark's Hospital, Harrow, UK
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46
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Wang T, Tsang T, Turshudzhyan A, Dacus H, Tadros M. Updates, Controversies, and Emerging Approaches in Colorectal Screening. Cureus 2021; 13:e17844. [PMID: 34660050 PMCID: PMC8501747 DOI: 10.7759/cureus.17844,] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/08/2021] [Indexed: 01/30/2025] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Despite the threatening statistics, the US burden for CRC has been decreasing, which is likely multifactorial and has partial contribution from widespread timely screening, more advanced CRC treatment, and daily aspirin use in some patients. While overall death rate from CRC decreased by approximately a half between 1975 and 2012, epidemiologic studies demonstrate that CRC incidence is increasing in the younger population. This pattern has prompted the American Cancer Society (ACS) to revise their guidelines. In this review, we plan to discuss the most recent changes in guidelines, data to support them, controversies concerning CRC screening methods, age to start and to stop screening, and post-colonoscopy/polypectomy surveillance guidelines.
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Affiliation(s)
- Tiffany Wang
- Internal Medicine, Albany Medical College, Albany, USA
| | - Tyler Tsang
- Internal Medicine, Albany Medical College, Albany, USA
| | | | - Heather Dacus
- Internal Medicine, New York State Department of Health, New York, USA
| | - Micheal Tadros
- Gastroenterology and Hepatology, Albany Medical Center, Albany, USA
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47
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Done JZ, Fang SH. Young-onset colorectal cancer: A review. World J Gastrointest Oncol 2021; 13:856-866. [PMID: 34457191 PMCID: PMC8371519 DOI: 10.4251/wjgo.v13.i8.856] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/30/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the general decrease in overall incidence of colorectal cancer since the early 1990s, the incidence of colorectal cancer in patients less than 50 years old has nearly doubled. A systematic review was performed using the PubMed database (2011-2020) and Cochrane Database of Systematic Reviews (2011-2021) to identify studies (published in English) evaluating epidemiologic, clinical, hereditary, and molecular features; as well as evaluation, management, and prognosis of young-onset colorectal cancer patients. Our search yielded a total of 3401 articles, after applying our inclusion criteria. We fully reviewed 94 full-length studies. This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.
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Affiliation(s)
- Joy Zhou Done
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD 21287, United States
| | - Sandy H Fang
- Department of Surgery, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD 21287, United States
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48
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Mendelsohn R, Palmaira RL, Lumish M, Bacani J, Krishnan A, Weiss J, Semler R, Casson A, Arkema A, Carter J, Nelson C, Mulhall J, Garcia-Aguilar J, Stadler Z, Maya H, Cercek A. A Coordinated Clinical Center for Young Onset Colorectal Cancer. Oncologist 2021; 26:625-629. [PMID: 34096669 DOI: 10.1002/onco.13849] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 05/25/2021] [Indexed: 12/20/2022] Open
Affiliation(s)
- Robin Mendelsohn
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Randze Lerie Palmaira
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Melissa Lumish
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Joseph Bacani
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Asha Krishnan
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jill Weiss
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Rosemary Semler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Anne Casson
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Ashley Arkema
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jeanne Carter
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.,Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Christian Nelson
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - John Mulhall
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Zsofia Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Hadley Maya
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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49
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Tang CT, Guo ZX, Wang P, Chen YX, Zeng CY. Higher LNM rate and poorer prognosis of early-onset compared to late-onset T1 stage colorectal cancer: a large-population based study. Am J Cancer Res 2021; 11:3176-3188. [PMID: 34249453 PMCID: PMC8263633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 03/17/2021] [Indexed: 06/13/2023] Open
Abstract
As for T1 stage CRC, there is little knowledge of differences in lymph node metastasis (LNM) and prognosis between early-onset and late-onset CRC. To know that, we included 13,084 patients from the SEER database and 476 patients in T1 stage from our hospital to analyze difference of LNM and prognosis. Univariate and multivariate logistic analyses revealed that early-onset CRC was more likely than late-onset CRC to be positive for LNM. In addition, we found that T1b stage, poor differentiation and lymphatic invasion were risk factors for LNM. Specifically, we found that black race was a risk factor. Before propensity-score matching (PSM), we also found that early-onset CRC patients had better survival, as demonstrated by SEER data. After adjusting for confounding factors by PSM, we found that early onset remained a risk factor for LNM. Moreover, we found that patients diagnosed with early-onset CRC had a poorer prognosis than those diagnosed with late-onset CRC, which was demonstrated by analysis of SEER data and our own data. In conclusion, our study was the first to find that early-onset T1 stage CRC more frequently developed LNM, suggesting that endoscopic submucosal resection should be performed more carefully in these patients. Moreover, early-onset patients in the T1 stage also had poorer survival, suggesting that clinical doctors should pay more attention to early-onset patients.
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Affiliation(s)
- Chao-Tao Tang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Zi-Xiang Guo
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Peng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - You-Xiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Chun-Yan Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
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50
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Dairi O, Anderson JC, Butterly LF. Why is colorectal cancer increasing in younger age groups in the United States? Expert Rev Gastroenterol Hepatol 2021; 15:623-632. [PMID: 33480301 DOI: 10.1080/17474124.2021.1876561] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: While colorectal cancer (CRC) incidence and mortality have decreased for older adults, the rates are increasing in adults younger than 50 years of age in the United States as well as globally. In response to strong epidemiologic evidence as well as sophisticated models, the American Cancer Society (ACS) has recommended screening adults for CRC starting at age 45. Understanding the factors associated with the rise of incidence in adults younger than age 50 may help to identify those adults who may be at greatest risk.Areas covered: In this review, we provide an overview of the recent literature and discuss possible explanations for the increase in CRC in young adults including obesity and other recognized CRC risk factors, delay in diagnosis of symptomatic patients (<50 years of age), and review perspectives on the current and future status of the field.Expert opinion: Currently there are little data regarding risk factors for CRC in average risk young adults who are asymptomatic. With potential endorsement of screening at 45 years of age by US Preventive Services Task Force, more data regarding clinical and molecular risk factors associated with CRC in young adults will be available.
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Affiliation(s)
- Obaida Dairi
- Department of Veterans Affairs Medical Center, White River Junction, VT and the Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Joseph C Anderson
- Department of Veterans Affairs Medical Center, White River Junction, VT and the Geisel School of Medicine at Dartmouth, Hanover, NH, USA.,Division of Gastroenterology and Hepatology, University of Connecticut School of Medicine, Farmington, CT, USA.,New Hampshire Colonoscopy Registry, Lebanon, NH, USA
| | - Lynn F Butterly
- New Hampshire Colonoscopy Registry, Lebanon, NH, USA.,Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
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