While the incidence of colorectal cancer (CRC) in the US has declined at a pace of 3% annually between 2003 and 2012, there has been an increase in the incidence of early-onset colorectal cancer (EOCRC). The reasons for this increase are unclear. Diet, the environment, the microbiome and alcohol consumption have all been proposed as contributing factors. There is the possibility that EOCRC has a unique biology. Overlapping with the EOCRC age range is CRC in adolescent and young adults (AYA) that share many molecular characteristics with EOCRC. The purpose of this review is to cover current progress in our understanding of the biology of CRC in the context of adolescent and young adult CRC and EOCRC and discuss future directions.
{"title":"Genomic and molecular alterations associated with early-onset and adolescent and young adult colorectal cancer","authors":"J. V. Tricoli","doi":"10.2217/crc-2020-0009","DOIUrl":"https://doi.org/10.2217/crc-2020-0009","url":null,"abstract":"While the incidence of colorectal cancer (CRC) in the US has declined at a pace of 3% annually between 2003 and 2012, there has been an increase in the incidence of early-onset colorectal cancer (EOCRC). The reasons for this increase are unclear. Diet, the environment, the microbiome and alcohol consumption have all been proposed as contributing factors. There is the possibility that EOCRC has a unique biology. Overlapping with the EOCRC age range is CRC in adolescent and young adults (AYA) that share many molecular characteristics with EOCRC. The purpose of this review is to cover current progress in our understanding of the biology of CRC in the context of adolescent and young adult CRC and EOCRC and discuss future directions.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43698992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Sandhu, R. Anders, P. Blatchford, A. Walde, A. Leal, G. King, S. Leong, S. L. Davis, W. Purcell, K. Goodman, T. Schefter, Michelle L. Cowan, W. Herter, C. Meguid, Reed Weiss, Megan D. Marsh, M. Brown, J. Vogel, E. Birnbaum, S. Ahrendt, A. Gleisner, R. Schulick, M. Chiaro, M. McCarter, Swati G. Patel, W. Messersmith, C. Lieu
Background: We examined characteristics of early-onset colorectal cancer (CRC) patients to identified factors, which may lead to earlier diagnosis. Materials & methods: This is a retrospective study with inclusion criteria: CRC diagnosed between 2012 and 2018 and age at diagnosis <50 years. Results: A total of 209 patients were included (mean age 41.8 years). Of those patients 42.5% had rectal cancer and 37.8% were stage IV at initial diagnosis. Of patients with data available for rectal bleeding history (n = 173), 50.8% presented with rectal bleeding and median time from onset of bleeding to diagnosis was 180 days (interquartile range 60–365), with longer duration noted in advanced cancer. Conclusion: Prolonged rectal bleeding history was noted in a significant proportion of early-onset CRC patients, with longer duration of rectal bleeding noted in stage IV patients. Patients and primary care physicians should be made aware of this finding in order to facilitate timely referral for diagnostic workup.
{"title":"High incidence of prolonged rectal bleeding and advanced stage cancer in early-onset colorectal cancer patients","authors":"G. Sandhu, R. Anders, P. Blatchford, A. Walde, A. Leal, G. King, S. Leong, S. L. Davis, W. Purcell, K. Goodman, T. Schefter, Michelle L. Cowan, W. Herter, C. Meguid, Reed Weiss, Megan D. Marsh, M. Brown, J. Vogel, E. Birnbaum, S. Ahrendt, A. Gleisner, R. Schulick, M. Chiaro, M. McCarter, Swati G. Patel, W. Messersmith, C. Lieu","doi":"10.2217/crc-2020-0012","DOIUrl":"https://doi.org/10.2217/crc-2020-0012","url":null,"abstract":"Background: We examined characteristics of early-onset colorectal cancer (CRC) patients to identified factors, which may lead to earlier diagnosis. Materials & methods: This is a retrospective study with inclusion criteria: CRC diagnosed between 2012 and 2018 and age at diagnosis <50 years. Results: A total of 209 patients were included (mean age 41.8 years). Of those patients 42.5% had rectal cancer and 37.8% were stage IV at initial diagnosis. Of patients with data available for rectal bleeding history (n = 173), 50.8% presented with rectal bleeding and median time from onset of bleeding to diagnosis was 180 days (interquartile range 60–365), with longer duration noted in advanced cancer. Conclusion: Prolonged rectal bleeding history was noted in a significant proportion of early-onset CRC patients, with longer duration of rectal bleeding noted in stage IV patients. Patients and primary care physicians should be made aware of this finding in order to facilitate timely referral for diagnostic workup.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/crc-2020-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46298953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In conversation with Editor Lauren Woolfe, J Tompkins shares her experience with early-onset colorectal cancer. From diagnosis and treatment, to adjusting to life as a survivor and being an ambassador for Fight Colorectal Cancer, this is J Tompkins’ story.
{"title":"Surviving early-onset colorectal cancer: a patient’s perspective","authors":"J. Tompkins","doi":"10.2217/crc-2020-0022","DOIUrl":"https://doi.org/10.2217/crc-2020-0022","url":null,"abstract":"In conversation with Editor Lauren Woolfe, J Tompkins shares her experience with early-onset colorectal cancer. From diagnosis and treatment, to adjusting to life as a survivor and being an ambassador for Fight Colorectal Cancer, this is J Tompkins’ story.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47167237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently, there has been an unexpected trend toward increased incidence of colorectal cancer in younger individuals, particularly distal colon and rectal cancer in those under age 50. There is evidence to suggest that the human gut microbiome may play a role in carcinogenesis. The microbiome is dynamic and varies with age, geography, ethnicity and diet. Certain bacteria such as Fusobacterium nucleatum have been implicated in the development of colorectal and other gastrointestinal cancers. Recent data suggest that bacteria can alter the inflammatory and immune environment, influencing carcinogenesis, lack of treatment response and prognosis. Studies to date focus on older patients. Because the microbiome varies with age, it could be a potential explanation for the rise in early-onset colorectal cancer.
{"title":"The gut microbiome and potential implications for early-onset colorectal cancer","authors":"Reetu Mukherji, B. Weinberg","doi":"10.2217/crc-2020-0007","DOIUrl":"https://doi.org/10.2217/crc-2020-0007","url":null,"abstract":"Recently, there has been an unexpected trend toward increased incidence of colorectal cancer in younger individuals, particularly distal colon and rectal cancer in those under age 50. There is evidence to suggest that the human gut microbiome may play a role in carcinogenesis. The microbiome is dynamic and varies with age, geography, ethnicity and diet. Certain bacteria such as Fusobacterium nucleatum have been implicated in the development of colorectal and other gastrointestinal cancers. Recent data suggest that bacteria can alter the inflammatory and immune environment, influencing carcinogenesis, lack of treatment response and prognosis. Studies to date focus on older patients. Because the microbiome varies with age, it could be a potential explanation for the rise in early-onset colorectal cancer.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/crc-2020-0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44600256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: To determine the impact of tumor sidedness on all-cause mortality for early- (age 18–49 years) and older-onset (age ≥50 years) colorectal cancer (CRC). Materials & methods: We conducted a retrospective study of 650,382 patients diagnosed with CRC between 2000 and 2016. We examined the associations of age, tumor sidedness (right colon, left colon and rectum) and all-cause mortality. Results: For early-onset CRC (n = 66,186), mortality was highest in the youngest age group (18–29 years), driven by left-sided colon cancers (vs 50–59 years, hazard ratio: 1.18; 95% CI: 1.03–1.34). 5-year risk of death among 18–29-year-olds with left-sided colon cancer (0.42, 95% CI: 0.38, 0.46) was higher than all other age groups. Conclusion: Left-sided colon cancers are enriched in younger adults and may be disproportionately fatal.
{"title":"Early-onset colorectal cancer: more than one side to the story","authors":"N. Sanford, Pooja Dharwadkar, C. Murphy","doi":"10.2217/crc-2020-0016","DOIUrl":"https://doi.org/10.2217/crc-2020-0016","url":null,"abstract":"Aim: To determine the impact of tumor sidedness on all-cause mortality for early- (age 18–49 years) and older-onset (age ≥50 years) colorectal cancer (CRC). Materials & methods: We conducted a retrospective study of 650,382 patients diagnosed with CRC between 2000 and 2016. We examined the associations of age, tumor sidedness (right colon, left colon and rectum) and all-cause mortality. Results: For early-onset CRC (n = 66,186), mortality was highest in the youngest age group (18–29 years), driven by left-sided colon cancers (vs 50–59 years, hazard ratio: 1.18; 95% CI: 1.03–1.34). 5-year risk of death among 18–29-year-olds with left-sided colon cancer (0.42, 95% CI: 0.38, 0.46) was higher than all other age groups. Conclusion: Left-sided colon cancers are enriched in younger adults and may be disproportionately fatal.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46035128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristin Wallace, Hong Li, C. Paulos, D. Lewin, A. Alekseyenko
Background: Survival is reduced in African–Americans (AAs) diagnosed with colorectal cancer (CRC), especially in those <50 years old, when compared with Caucasian Americans (CAs). Yet, the role of clinicopathologic features of CRCs on racial differences in survival needs further study. Materials & methods: Over 1000 individuals (CA 709, AA 320) diagnosed with CRC were studied for survival via the Cox proportional hazards regression analysis based on race and risk of death in two age groups (<50 or 50+). Results: Risk of death for younger AAs (<50) was elevated compared with younger CAs (hazard ratio [HR] 1.98 [1.26–3.09]). Yet no racial differences in survival was observed in older cohort (50+ years), HR 1.07 (0.88–1.31); p for interaction = 0.01. In younger AAs versus CAs only, colonic location attenuated the risk of death. Conclusion: The tumor location and histology influence the poorer survival observed in younger AAs suggesting these may also influence treatment responses.
背景:与高加索美国人(CAs)相比，非洲裔美国人(AAs)诊断为结直肠癌(CRC)的生存率降低，尤其是那些<50岁的人。然而，CRCs的临床病理特征在种族生存差异中的作用需要进一步研究。材料与方法:通过基于种族和两个年龄组(<50岁或50岁以上)死亡风险的Cox比例风险回归分析，研究了1000多例确诊为结直肠癌的患者(CA 709, AA 320)的生存率。结果:年龄<50岁的AAs与年龄较小的CAs相比死亡风险升高(风险比[HR] 1.98[1.26-3.09])。然而，在年龄较大的队列(50岁以上)中，生存率没有种族差异，HR为1.07 (0.88-1.31);交互作用P = 0.01。在年轻的AAs和ca中，结肠位置降低了死亡风险。结论:肿瘤的位置和组织学影响年轻AAs患者较差的生存率，这也可能影响治疗反应。
{"title":"Racial disparity in survival of patients diagnosed with early-onset colorectal cancer","authors":"Kristin Wallace, Hong Li, C. Paulos, D. Lewin, A. Alekseyenko","doi":"10.2217/crc-2020-0015","DOIUrl":"https://doi.org/10.2217/crc-2020-0015","url":null,"abstract":"Background: Survival is reduced in African–Americans (AAs) diagnosed with colorectal cancer (CRC), especially in those <50 years old, when compared with Caucasian Americans (CAs). Yet, the role of clinicopathologic features of CRCs on racial differences in survival needs further study. Materials & methods: Over 1000 individuals (CA 709, AA 320) diagnosed with CRC were studied for survival via the Cox proportional hazards regression analysis based on race and risk of death in two age groups (<50 or 50+). Results: Risk of death for younger AAs (<50) was elevated compared with younger CAs (hazard ratio [HR] 1.98 [1.26–3.09]). Yet no racial differences in survival was observed in older cohort (50+ years), HR 1.07 (0.88–1.31); p for interaction = 0.01. In younger AAs versus CAs only, colonic location attenuated the risk of death. Conclusion: The tumor location and histology influence the poorer survival observed in younger AAs suggesting these may also influence treatment responses.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48754500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colorectal cancer (CRC) in individuals under the age of 50 is a problem that is increasing in USA and around the world. In this review, we discuss the degree to which early-onset (EO)CRC may be due to unsuspected Lynch syndrome or other inherited germline variants that predispose to cancer, describe the known somatic genetic alterations in EO tumors and discuss alterations in DNA methylation. Approximately 20% of EOCRCs can be attributed to identifiable germline mutations in genes that cause familial cancer syndromes. A variety of other genetic/epigenetic alterations have also been reported. We conclude that this is a heterogeneous problem, that requires a comprehensive analysis of genetic/epigenetic signatures to better understand EOCRC. Various subsets of EOCRCs must be analyzed individually for clues regarding the etiologies and possible specific therapies for this disease.
{"title":"The genetic and epigenetic landscape of early-onset colorectal cancer","authors":"C. Boland, A. Goel, Swati G. Patel","doi":"10.2217/crc-2020-0005","DOIUrl":"https://doi.org/10.2217/crc-2020-0005","url":null,"abstract":"Colorectal cancer (CRC) in individuals under the age of 50 is a problem that is increasing in USA and around the world. In this review, we discuss the degree to which early-onset (EO)CRC may be due to unsuspected Lynch syndrome or other inherited germline variants that predispose to cancer, describe the known somatic genetic alterations in EO tumors and discuss alterations in DNA methylation. Approximately 20% of EOCRCs can be attributed to identifiable germline mutations in genes that cause familial cancer syndromes. A variety of other genetic/epigenetic alterations have also been reported. We conclude that this is a heterogeneous problem, that requires a comprehensive analysis of genetic/epigenetic signatures to better understand EOCRC. Various subsets of EOCRCs must be analyzed individually for clues regarding the etiologies and possible specific therapies for this disease.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/crc-2020-0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47773262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Brockway-Lunardi, Stefanie A. Nelson, A. Pandiri, J. V. Tricoli, A. Umar, A. Wali, Phillip J. Daschner
The incidence rates of sporadic early-onset colorectal cancer (EO-CRC) are increasing rapidly in the USA and globally. Birth cohort analyses strongly suggest that changes in early life exposures to known or unknown risk factors for CRC may be driving EO disease, but the etiology of EO-CRC remains poorly understood. To address the alarming rise in sporadic EO-CRC, the National Cancer Institute and National Institute of Environmental Health Sciences convened a virtual meeting that featured presentations and critical discussions from EO-CRC experts that examined emerging evidence on potential EO-CRC risk factors, mechanisms and translational opportunities in screening and treatment.
{"title":"Early-onset colorectal cancer research: gaps and opportunities","authors":"Laura Brockway-Lunardi, Stefanie A. Nelson, A. Pandiri, J. V. Tricoli, A. Umar, A. Wali, Phillip J. Daschner","doi":"10.2217/crc-2020-0028","DOIUrl":"https://doi.org/10.2217/crc-2020-0028","url":null,"abstract":"The incidence rates of sporadic early-onset colorectal cancer (EO-CRC) are increasing rapidly in the USA and globally. Birth cohort analyses strongly suggest that changes in early life exposures to known or unknown risk factors for CRC may be driving EO disease, but the etiology of EO-CRC remains poorly understood. To address the alarming rise in sporadic EO-CRC, the National Cancer Institute and National Institute of Environmental Health Sciences convened a virtual meeting that featured presentations and critical discussions from EO-CRC experts that examined emerging evidence on potential EO-CRC risk factors, mechanisms and translational opportunities in screening and treatment.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48841275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Lowery, T. Weber, D. Ahnen, Paul C. Schroy III, Caleb L Levell, Robert A. Smith
Aim: The National Colorectal Cancer Roundtable convened a national Summit to discuss the causes of early-onset colorectal cancer and clinical challenges to mitigating burden of this disease. Materials & methods: Information presented was synthesized through scientific consensus building to determine priorities for new research and practice change. Results: Research priorities include evaluating role of novel risk factors, understanding natural history and identifying ways to implement evidenced-based practices for identifying and managing at-risk persons. Practice change should focus on adoption of guidelines for collecting family history, screening in young adults at risk, provider and population awareness about risk and symptoms, and universal tumor testing. Conclusion: Successful implementation of strategies to address research and practice change will require collaboration from multiple partners.
{"title":"An action plan to address the rising burden of colorectal cancer in younger adults","authors":"J. Lowery, T. Weber, D. Ahnen, Paul C. Schroy III, Caleb L Levell, Robert A. Smith","doi":"10.2217/crc-2020-0004","DOIUrl":"https://doi.org/10.2217/crc-2020-0004","url":null,"abstract":"Aim: The National Colorectal Cancer Roundtable convened a national Summit to discuss the causes of early-onset colorectal cancer and clinical challenges to mitigating burden of this disease. Materials & methods: Information presented was synthesized through scientific consensus building to determine priorities for new research and practice change. Results: Research priorities include evaluating role of novel risk factors, understanding natural history and identifying ways to implement evidenced-based practices for identifying and managing at-risk persons. Practice change should focus on adoption of guidelines for collecting family history, screening in young adults at risk, provider and population awareness about risk and symptoms, and universal tumor testing. Conclusion: Successful implementation of strategies to address research and practice change will require collaboration from multiple partners.","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47614585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An interview with Ann Zauber","authors":"A. Zauber","doi":"10.2217/crc-2020-0029","DOIUrl":"https://doi.org/10.2217/crc-2020-0029","url":null,"abstract":"","PeriodicalId":43638,"journal":{"name":"Colorectal Cancer","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46148039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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