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Статті в журналах з теми "Young-onset colorectal cancer"

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Автор: Grafiati

Опубліковано: 10 грудня 2022

Оновлено: 28 січня 2023

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1

Done, Joy Zhou, and Sandy H. Fang. "Young-onset colorectal cancer: A review." World Journal of Gastrointestinal Oncology 13, no. 8 (August 15, 2021): 856–66. http://dx.doi.org/10.4251/wjgo.v13.i8.856.

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2

Rosato, Valentina, Cristina Bosetti, Fabio Levi, Jerry Polesel, Antonella Zucchetto, Eva Negri, and Carlo La Vecchia. "Risk factors for young-onset colorectal cancer." Cancer Causes & Control 24, no. 2 (December 8, 2012): 335–41. http://dx.doi.org/10.1007/s10552-012-0119-3.

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3

Lee, Lucas D., and Y. Nancy You. "Young-onset colorectal cancer: Diagnosis and management." Seminars in Colon and Rectal Surgery 29, no. 3 (September 2018): 98–101. http://dx.doi.org/10.1053/j.scrs.2018.06.002.

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4

Mauri, Gianluca, Andrea Sartore‐Bianchi, Antonio‐Giampiero Russo, Silvia Marsoni, Alberto Bardelli, and Salvatore Siena. "Early‐onset colorectal cancer in young individuals." Molecular Oncology 13, no. 2 (December 22, 2018): 109–31. http://dx.doi.org/10.1002/1878-0261.12417.

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5

Stoffel, Elena Martinez, Julie Ruterbusch, Laura S. Rozek, and Michele L. Cote. "Racial disparities in survival after young-onset colorectal cancer." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 524. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.524.

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524 Background: Despite overall reductions in morbidity and mortality from colorectal cancer (CRC), racial disparities persist. In addition, incidence among individuals age <50 is rising. Our aim was to compare survival of young onset CRC cases diagnosed in black and white individuals. Methods: Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program we identified individuals with CRC between the ages of 20 to 49, diagnosed in 2000-2008. Kaplan-Meier and Cox proportional hazards models were used to compare stage-specific 5 year survival between black and white individuals with young onset CRC. Results: A total of 26,236 incident young onset CRC cases (22,121 white, 4,115 black) were identified during the 9 year study period. Overall survival at 5 years following CRC diagnosis was 54.8% among blacks and 67.4% among whites (p<0.001), with blacks having a significantly higher hazard of death after adjusting for age, sex, stage, tumor site, and treatment history (HR 1.34, 95% CI 1.26-1.43). Stratifying by stage at CRC diagnosis, blacks had worse survival at every disease stage compared with whites, with the greatest racial disparities observed among stage II cancers of colon (HR 1.68 95% CI 1.38-2.04) and stage II and III cancers of the rectum (HR 1.78, 95% CI 1.51-2.09, and HR 1.86, 95% CI 1.54-2.24, respectively). Conclusions: Survival after diagnosis of CRC at young age is significantly worse among blacks compared to whites, even among individuals with early stage disease. These findings suggest that differences in tumor biology may play a role in racial disparities in CRC outcomes, which may have implications for adjuvant treatment.

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6

Baraibar, Iosune, Francesc Salva, Raquel Comas, Javier Ros, Ariadna Garcia, Mireia Sanchis, Jose Luis Cuadra, et al. "Young-onset colorectal cancer: A call for action." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10563. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10563.

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10563 Background: Young-onset colorectal cancer (YOCR) is defined as diagnosis below the age of 50. Over the past decades, the incidence of YOCRC has increased at an alarming rate, but causes and pathogenesis still remain unknown. Early detection of colorectal cancer (CRC) has demonstrated to improve survival. Despite these facts, adults < 50 years old are not yet included in screening programs and YOCRC is not well characterized. We aimed to characterize the clinical and molecular characteristics of YOCRC in patients (pts) diagnosed at our institution. Methods: Consecutive pts with a diagnosis of CRC below the age of 50 visited for the first time at Vall d’Hebron University Hospital in Spain between January 2017 and October 2020 were included in the analysis. Data of clinicopathologic features and treatment were collected retrospectively from medical records. Results: 205 pts met the inclusion criteria, 111 (54%) were females, 8 (4%) presented a personal history of cancer at diagnosis and 109 (53%) a family history of cancer. Age at diagnosis was: < 30: 10 (5%), {30 – 40): 52 (25%), {40-45): 51 (25%), {45-50): 92 (45%). Site of primary tumor was: right colon: 50 (24%), left colon: 107 (52%): rectum: 48 (24%). Stage at diagnosis was I: 3 (1%), II: 14 (7%), III: 60 (29%), IV: 128 (63%). 6 of 14 (43%) and 44 of 60 patients (73%) with stage II and III CRC presented disease progression after initial treatment, respectively. Molecular status was: KRAS mutation: 74 (36%), NRAS mutation: 7 (3%), BRAF mutation: 12 (6%), MSI-H: 12 (6%). 43 pts (21%) had documentation of genetic counseling. Median (range) number of lines of treatment for metastatic disease was 3 (1-7), 53 pts (30%) received at least 4 lines of treatment. Median (range) number of metastatic sites was: 2 (1-6). 114 patients (55.6%) had died at the cut-off timepoint. Conclusions: YOCR is usually diagnosed with a more advanced stage than standard-onset CRC, with a poorer course of the disease. Further studies in young adults with CRC should address this phenomenon to understand the underlying causes, and prioritize genetic counseling. Our results support the unmet need of initiating screening programs in adults younger than 50 years, the urgency for a global consensus and a call for action.

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7

Neufeld, D., B. Shpitz, N. Bugaev, M. Grankin, J. Bernheim, E. Klein, and Y. Ziv. "Young-age onset of colorectal cancer in Israel." Techniques in Coloproctology 13, no. 3 (July 16, 2009): 201–4. http://dx.doi.org/10.1007/s10151-009-0501-7.

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8

Jayakrishnan, Thejus, Nicole Farha, Arshiya Mariam, Daniel Miller Rotroff, Federico Aucejo, Shimoli V. Barot, Madison Conces, et al. "Metabolomic differences in young-onset versus average-onset colorectal adenocarcinoma." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 174. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.174.

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174 Background: Novel deleterious effects of environmental exposures may play a role in the rising incidence of young-onset colorectal cancer (yoCRC). We used metabolomics to assess differences between yoCRC and average-onset CRC (aoCRC), in comparison to healthy controls, which may suggest certain exposure risks. Methods: Patients with stage I-IV CRC and healthy controls were identified from prospective biobanks and categorized based on age<50 years (yoCRC or young controls) or age>60 years (aoCRC or older controls). Serum metabolites were profiled using GC-TOF mass spectrometry. Differential abundance of metabolites was investigated using unadjusted logistic regression. Metabolic pathway analysis was performed using Metaboanalyst 5.0. All p-values were adjusted for multiple testing (false-discovery rate, FDR p<0.20 considered significant). Results: The study population comprised 170 CRC patients (66 yoCRC and 104 aoCRC) and 49 healthy controls (34 young and 15 old). Association analyses revealed four differentially abundant metabolites: citrate (FDR p=0.04), cholesterol (0.14), and two unidentified metabolites (UM). Metabolic pathways significantly altered in yoCRC vs. aoCRC included: carbohydrate metabolism (citrate cycle, FDR p=0.11), carbohydrate biosynthesis (glyoxylate and dicarboxylate metabolism, FDR p=0.03), amino-acid metabolism (alanine, aspartate, and glutamate metabolism, FDR p=0.04, arginine biosynthesis, FDR p=0.04, and amino-acid t-RNA biosynthesis, FDR p=0.04). There were no significant metabolomic differences between young and older controls. Conclusions: We identified significant differences in the citrate cycle - a core pathway of cellular metabolism and associated with colorectal cancer. Metabolomic differences in pathways of carcinogenic significance (aspartate) and environmental exposures (arginine and dietary red meat) were also noted, suggesting potential relationships with younger age of CRC onset. The study provides future directions for more precise analyses with a larger sample size for healthy controls and adjusting for confounders. [Table: see text]

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9

Nwe, Khin Khin. "Colorectal cancer in young population: Yangon, Myanmar." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14055-e14055. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14055.

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e14055 Background: CRC is the tenth most common cause of cancer in 2006 Myanmar Cancer Statistic. Recently, increased incidence of CRC among young age has been seen in our population. Methods: Demographic data of CRC pts registered in medical oncology unit, YGH from January 2009 to September, 2011 were studied. Age under 40 yrs was considered as a young patient. Stage distribution were analyzed to study about young onset CRC pattern. Results: Among 351 CRC patients registered, 120pts (34.19%) were under 40 yrs old. In young age group, age range from 12 to 40 yrs (median 29.5 yrs). Male to female ration was 1:1.26. Left-sided cancer (splenic flexure to rectum) in 93 patients (77.5%) and right sided (caecum to transverse colon) cancer in 27 pts (22.5%). Six pts (5%) were stage I, 41 people (34.17%) with stage II. Forty-four patients (36.67%) were node positive Stage III and 29 people (24.17%) with distant metastasis, Stage IV. Conclusions: Three percent of colorectal cancers occur in patients younger than 40 years of age in World Cancer Data. However, one third of CRC pts registered within 3 yrs in our unit were under age 40.The commonest stage seen in those pts were stage III at initial diagnosed. According to this data, younger onset of CRC in Myanmar is increasing although it doesn’t reflect the whole population. Further larger study is required to prove it. [Table: see text]

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10

Vadehra, Deepak, Beas Siromoni, Adrienne Groman, and Sarbajit Mukherjee. "Exploring demographic differences and outcomes in young-onset colorectal cancer." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 35. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.35.

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35 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States (1). The incidence of young-onset CRC is on the rise based on recent data (2). Previous research on other cancers has shown that patients living in rural areas have worse outcomes (3). This study aimed to investigate the geographic and socio-demographic disparities in young-onset CRC patients. Methods: We conducted a retrospective study on colorectal cancer patients between 1975 and 2016 using the Surveillance, Epidemiology, and End Results (SEER) database. Both univariate and multivariable analyses were performed to evaluate overall survival (OS) and disease-specific survival (DSS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. Young-onset colorectal cancer (CRC) was defined as the age of diagnosis less than 50 years. The program used for analysis was SAS software 9.4 (SAS Institute Inc., Cary, NC, USA.) Univariate and multivariable models were analyzed using Cox proportional models. Demographic differences between urban and rural population were assessed using Wilcoxon Rank Sum test (continuous variable) and Chi-square test (categorical variables). Results: A total of 73,378 [RA, N = 7,636(10.6%); MA, N = 64,605(89.4%)] young-onset CRC patients were included. RA had more Caucasian patients compared to MA (80.5% vs 60%, p < 0.001). Patients living in RA were more likely to be uninsured (4.8% vs 3%, p < 0.001) than MA. During the study period, the incidence and mortality rates were consistently higher in RA vs. MA. Univariate and multivariable analysis showed that RA had worse OS (multivariate HR = 1.14; p < 0.01) and DSS (multivariate HR = 1.15; p < 0.001) compared to MA. Similarly, males, single and uninsured patients had worse OS and DSS compared to females, married, and insured patients, respectively. Conclusions: Our study identified social and demographic disparities in young-onset CRC incidence and outcomes. Potential causes may include access to healthcare, diet, health behavior, and environmental factors. Future research is needed to understand and attenuate such disparities.

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11

Goh, Serene SN, Edith XL Loo, and Daniel JK Lee. "Trends and Clinical Outcomes in Young-onset Colorectal Cancer Patients." Annals of the Academy of Medicine, Singapore 49, no. 11 (November 30, 2020): 848–56. http://dx.doi.org/10.47102/annals-acadmedsg.20207.

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Introduction: Young individuals with colorectal cancer (CRC) tend to be diagnosed at advanced stages and are not routinely included in screening programmes. This study describes the incidence, disease pattern and factors affecting overall survival in young- onset CRC. Methods: A retrospective study of young-onset CRC patients diagnosed between 2010 and 2017 in a tertiary hospital was conducted. Results: There were 99 patients, 69.7% had left-sided while 30.3% had right-sided CRC. The mean age was 43.3 years (43.3±5.0) and 62 patients (62.6%) were male. The incidence of young-onset CRC has been on the rise since 2014. Out of 99 patients, 65 (65.7%) underwent elective surgery, 30 (30.3%) underwent emergency surgery and the remainder 5 (4.0%) were palliated. The most common presenting complaints for patients who underwent elective surgery were abdominal pain, per-rectal bleeding and altered bowel habits. For patients who required emergency surgery, 20 (66.6%) presented with intestinal obstruction and 10 (33.3%) had intestinal perforation. There were 42 (42.4%) stage III CRC and 20 (20.2%) stage IV CRC. The most frequent metastatic site was the liver (20/20, 100%). Five patients had signet ring cells (5.1%) in their histology while 15 (15.2%) had mucinous features. The overall 5-year survival of young-onset CRC was 82.0%. Advanced overall stage (hazard ratio (HR) 6.1, CI 1.03–3.62) and signet ring histology (HR 34.2, CI 2.24–5.23) were associated with poor prognosis. Conclusion: Young-onset CRC tend to be left-sided with advanced presentations. However, their 5-year survival remains favourable as compared to the general population. Keywords: Colorectal screening in the young, early-onset colorectal cancer, signet ring cell colorectal cancer

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12

Ballester, Veroushka. "Clinical and molecular features of young-onset colorectal cancer." World Journal of Gastroenterology 22, no. 5 (2016): 1736. http://dx.doi.org/10.3748/wjg.v22.i5.1736.

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13

Mendelsohn, Robin, Randze Lerie Palmaira, Melissa Lumish, Joseph Bacani, Asha Krishnan, Jill Weiss, Rosemary Semler, et al. "A Coordinated Clinical Center for Young Onset Colorectal Cancer." Oncologist 26, no. 8 (June 17, 2021): 625–29. http://dx.doi.org/10.1002/onco.13849.

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14

Newcomer, Kim Lynn, Ronit Yarden, and Danielle Peterson. "Gaps in caregiving for young-onset colorectal cancer patients." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 82. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.82.

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82 Background: The rise of young-onset colorectal cancer (YO-CRC) is an alarming public health issue. Interestingly, the proportion of new cases diagnosed in young people (20-49) had increased from 6% in 1990 to 11% in 2013 and coincides with the declining CRC cases in older people. YO-CRC patients face unique clinical challenges as many are diagnosed at advanced stages of the disease and subjected to aggressive treatments. In addition, diagnosis often disrupts early family and career developmental tasks and goals, suggesting the need for additional psychosocial support. Caregivers are an important part of the patient journey. Caregivers serve as liaisons with the medical community and the patient’s social network. The goal of this study is to cast light and explore the experience of caregivers who were caring for YO-CRC patients. Methods: The online survey was completed by 208 caregivers, diverse in age, gender, and race/ethnicity. Participants indicated their relationship as either: spouse/partner, parents, siblings, children, and non-family members. Results: Caregivers self-report they do not understand the important aspects of patients' medical needs despite 79% of caregivers are college graduates and 43% had an advanced degree. Most of the respondents (76%) lack understanding about treatment options and 56% did not feel confident they understood healthcare decisions. Overall, caregivers needed more information and guidance for managing the side-effects of treatment, A majority of caregivers (93%) reported fatigue due to lack of sleep and 63% reporting they missed eight hours or more of work each month. Participants (73%) reported they needed help for panic and anxiety and employed different coping mechanisms to deal with the toll of caregiving. Conclusions: Our survey indicates we must recognize caregivers as the patient's healthcare partners and engage them in the entire plan of care. A growing population of YO-CRC patients means a growing population of caregivers who are navigating work, parenthood, impacts on sexual health, and role changes right along with that patient. Such understanding could help in developing appropriate interventions for caregivers aimed at reducing their burden and stress in caring for patients with YO-CRC.

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15

Kyaw, Moe, and Joseph JY Sung. "Young‐onset colorectal cancer in the Asia–Pacific region." Medical Journal of Australia 205, no. 10 (November 2016): 450–51. http://dx.doi.org/10.5694/mja16.00957.

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16

Sung, Joseph J. Y., Han-Mo Chiu, Kyu-Won Jung, Jae Kwan Jun, Masau Sekiguchi, Takahisa Matsuda, and Moe H. Kyaw. "Increasing Trend in Young-Onset Colorectal Cancer in Asia." American Journal of Gastroenterology 114, no. 2 (February 2019): 322–29. http://dx.doi.org/10.14309/ajg.0000000000000133.

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17

Morita, Daisuke, Yozo Nakazawa, Miyuki Tanaka, Yoshiko Nakayama, Tomonobu Koizumi, and Kenichi Koike. "Early-onset colorectal cancer in young adult survivors of childhood cancer." Pediatrics International 58, no. 7 (April 13, 2016): 637–39. http://dx.doi.org/10.1111/ped.12900.

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18

Holowatyj, Andreana N., Julie J. Ruterbusch, Laura S. Rozek, Michele L. Cote, and Elena M. Stoffel. "Racial/Ethnic Disparities in Survival Among Patients With Young-Onset Colorectal Cancer." Journal of Clinical Oncology 34, no. 18 (June 20, 2016): 2148–56. http://dx.doi.org/10.1200/jco.2015.65.0994.

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Purpose Racial disparities in colorectal cancer (CRC) persist, despite overall reductions in morbidity and mortality. In addition, incidence is rising among individuals younger than 50 years of age. We compared the survival of young-onset CRC among non-Hispanic black (NHB), non-Hispanic white (NHW), and Hispanic individuals. Patients and Methods Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results program data, we identified individuals between the ages of 20 and 49 years, diagnosed with CRC between 2000 and 2009. Survival rates and Cox proportional hazards models were used to compare stage-specific 5-year survival among NHBs, NHWs, and Hispanics. Results We identified 28,145 patients with young-onset CRC (19,497 NHW; 4,384 NHB; 4,264 Hispanic) during the 10-year study period. Overall survival at 5 years after CRC diagnosis was 54.9% among NHB, 68.1% among NHW, and 62.9% among Hispanic individuals (P < .001). NHB individuals had a significantly higher hazard of cancer-specific death compared with NHWs after adjusting for age, sex, race, stage, county-level poverty, and treatment history in cases of colon (hazard ratio [HR], 1.35; 95% CI 1.26 to 1.45) and rectum/rectosigmoid junction (HR, 1.51; 95% CI, 1.37 to 1.68) cancers, whereas there was no significant difference in survival between NHWs and Hispanics. The greatest racial disparities in cancer-specific survival were observed among NHB and NHW patients diagnosed with stage II cancers of the colon (HR, 1.69; 95% CI, 1.33 to 2.14) and stage III cancers of the rectum (HR, 1.98; 95% CI, 1.63 to 2.40). Conclusion Survival after CRC diagnosis at a young age is significantly worse among NHBs compared with NHWs, even among patients with early-stage disease. Further study is needed to determine whether differences in tumor biology and/or treatment are associated with racial disparities in outcomes, which would have implications for CRC treatment and prevention.

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19

Peacock, Oliver, Yun Yang, Selvi Thirumurthi, Sa Thi Nguyen Nguyen, Phillip Lum, Miguel A. Rodriguez-Bigas, Brian K. Bednarski, et al. "Metachronous colorectal pathology among survivors of young-onset colorectal cancer: Implications for postresection colonoscopic surveillance." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 64. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.64.

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64 Background: Patients with sporadic young-onset colorectal cancer (CRC) are postulated to have a more biologically active colorectum prone to malignant transformation earlier in life. It is unknown whether there is elevated risk for metachronous colorectal pathology after the index cancer. We aimed to define this risk, to inform their post-resection endoscopic surveillance. Methods: Consecutive CRC patients (aged 18-50, n = 728) were prospectively followed after surgical resection between 2009 and 2017. Patients presenting with hereditary CRC, recurrent disease, or without endoscopy follow-up were excluded. All endoscopy records were subjected to natural language processing and further reviewed. Metachronous colorectal pathology of interest included: high-risk adenoma (≥1cm in size, > 3 in number, or tubulovillious/high-grade dysplasia histology), second CRC, and endoscopically detectable local recurrence. Results: During a 48-month (median) follow-up, 457 patients underwent 1,192 person-years of colonoscopic follow-up. The median age at CRC diagnosis was 44 years. Disease arose from the proximal colon in 9.4%, distal colon in 23.0% and rectum in 67.6%, and was stages I/II in 191 (41.8%), III in 185 (40.4%), and IV in 81 (17.7%). The majority (95.8%) underwent segmental resection, while the remainder had extended resections for synchronous pathology not amendable to preoperative endoscopic clearance. The overall incidence of metachronous pathology was 32 per 1000 person-years: 31 patients developed high-risk adenomas (6.8%), 1 had a second CRC (0.2%), and 7 had luminal recurrences (1.5%). The median time to metachronous pathology was 13.9 (IQR: 11.8-33.1) months, with 21 (53.8%) detected between 12 and 48 months post-resection. Conclusions: For young-onset CRC survivors, the incidence of metachronous colorectal pathology was 32 per 1000 person-years of follow-up. Given the time pattern of detection, adding an interval colonoscopy between the current recommended post-resection surveillance at 12 and 48 months may be beneficial. [Table: see text]

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Torrejon, Nataly Valeria, Saarang Deshpande, Wei Wei, Katherine Tullio, Shimoli V. Barot, Kanika G. Nair, Smitha S. Krishnamurthi, et al. "Comparison of comprehensive genomic profiles between young-onset and average-onset colorectal cancer." Journal of Clinical Oncology 40, no. 4_suppl (February 1, 2022): 167. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.167.

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167 Background: The incidence of young-onset colorectal cancer (yoCRC) is rising for unknown reasons. This study assessed for differences in comprehensive genomic profiles between yoCRC and average-onset colorectal cancer (aoCRC). Methods: All patients with CRC seen at Cleveland Clinic that had tumor-based next generation sequencing (NGS) performed as part of their care with a clinically available assay between January 2017 and September 2020 were included. The cohort was divided based on age of diagnosis, with yoCRC defined as age of CRC diagnosis <50 years old. All clinical data and genomic alterations were included for analysis. We assessed for differences in clinical data and NGS findings between yoCRC and aoCRC using Fisher’s exact test, adjusted for primary tumor sidedness. Overall survival (OS) by genomic alteration was estimated by Kaplan-Meier methods and compared using log rank test. Results: The study population comprised of 51 yoCRC patients and 211 aoCRC patients. There were no significant differences in sex, race or ethnicity between yoCRC and aoCRC patients. Compared to aoCRC patients, yoCRC patients were more likely to present at diagnosis with stage IV disease (81% vs. 56%, p = 0.02) and have left-sided primary tumors (69% vs. 60%, p = 0.26). YoCRC tumors were more likely to have mutations in APC, KRAS, TP53 and FLT3 compared to aoCRC tumors, independent of tumor sidedness. These data are summarized in Table. Compared to left-sided tumors, right-sided tumors had significantly higher frequency of KRAS (67.7% vs. 48.8%, p = 0.003), BRAF (15.2% vs. 3.1%, p = 0.0006) and PTEN (16.2% vs. 3.1%, p value = 0.0003) alterations. AoCRC patients had significantly longer OS compared to yoCRC patients (median OS: 70.0 months vs. 36.3 months, p=0.004). Black (37.2 months, n=35) and Asian (37.8 months, n=7) patients had significantly worse median OS compared to White patients (67.8 months, n=199), p-value 0.005. In the overall population, patients with APC mutations had significantly better OS compared to those with APC wildtype tumors (median OS: 92.6 months vs. 54.4 months, p=0.001). Patients with FLT3 mutations had worse median OS compared to those with FLT3 wildtype tumors (median OS: 42.0 months vs. 64.8 months, p=0.007). There were no survival differences based on MSI status. Conclusions: In this series, yoCRC patients were more likely to present with stage IV disease and experienced worse OS compared to aoCRC patients. YoCRC patients were more likely to have mutations in APC, KRAS, TP53 and FLT3, independent of tumor sidedness. Mutations in FLT3 correlated with worse OS.[Table: see text]

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Dave, Heloni M., Naseer Sangwan, Kanika G. Nair, Shimoli V. Barot, David Liska, Stephanie Schmit, and Alok A. Khorana. "Racial disparities in tumor microbiome in young-onset and average-onset colorectal cancer." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 13. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.13.

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13 Background: The occurrence of young-onset colorectal cancer (yoCRC) is rising alarmingly, with a disproportionate incidence in Black patients as compared to White. We and others have previously shown differences in tumor microbiomes between yoCRC and average-onset colorectal cancer (aoCRC), but it is unknown if these differences contribute to racial disparities. We therefore analyzed racial differences in the intra-tumoral microbiome of CRC in young adults (<50 years). Methods: We analyzed 277 samples of histologically confirmed cases of stage I-IV CRC patients identified as either non-Hispanic Black or non-Hispanic White, who underwent surgical resection at Cleveland Clinic from year 2000-2020, who consented to a prospective biorepository. Fresh frozen specimens from the primary tumor with paired adjacent nonmalignant tissue were analyzed. The 16s rRNA gene was amplified and sequenced using V4 region primers and Illumina’s MiSeq system. Using DADA2, the quality filtered 16S rRNA amplicon reads were clustered and annotated as amplicon sequence variants (ASVs). The abundance count matrix was analyzed for alpha and beta diversity and differential abundance analysis (DAA) using Phyloseq package. Statistical tests included analysis of variance (ANOVA), permutational multivariate analysis (PERMANOVA), linear regression and Wilcoxon test. DAA and correlation analysis were controlled for false discovery rate using Benjamini Hochberg correction. Results: Differential abundance analysis highlighted key differences in the microbiome composition of Black and White patients with yoCRC. Amongst Black patients, the most prevalent taxa were Limosilactobacillus, Bacillus, Staphylococcus, Listeria and Akkermansia, whereas amongst White patients the most prevalent taxa were Enterococcus and Escherichia-Shigella (Table). Microbial profiles were also significantly different between Black patients with yoCRC and aoCRC and between White patients with yoCRC and aoCRC. At ASV level, the microbiome of Black yoCRC is more similar (R2 =0.87) to Black aoCRC, in comparison to white yoCRC (R2=0.57). Conclusions: We found significant differences between the intra-tumoral microbiome of yoCRC in the United States by race. Future epidemiologic studies and public health interventions need to account for these differences to reduce risk of yoCRC across various US populations. [Table: see text]

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He, Xingkang, Wenrui Wu, Yu'e Ding, Yue Li, Jianmin Si, and Leimin Sun. "Excessive risk of second primary cancers in young-onset colorectal cancer survivors." Cancer Medicine 7, no. 4 (March 13, 2018): 1201–10. http://dx.doi.org/10.1002/cam4.1437.

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Aday, Ulas, Mehmet T. Kafadar, Abdullah Oğuz, Mehmet V. Bahadır, Baran Demir, Faik V. Akpulat, Baris Gulturk, and Abdullah Böyük. "Polyposis and Oncologic Outcomes in Young-onset Sporadic Colorectal Cancer." Euroasian Journal of Hepato-Gastroenterology 11, no. 1 (2021): 6–10. http://dx.doi.org/10.5005/jp-journals-10018-1334.

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Goksu, Suleyman Yasin, Jude Khatib, Sarah Reddy, Muhammet Ozer, Mary Claire Maxwell, Leticia Khosama, Radhika Kainthla, et al. "Association between environmental quality index and young onset colorectal cancer." Journal of Clinical Oncology 40, no. 4_suppl (February 1, 2022): 75. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.075.

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75 Background: The factors associated with the rise of young-onset colorectal cancer (YOCRC) remain unclear. In addition to hereditary factors, environmental exposures are believed to be associated with YOCRC. Therefore, we aimed to study the association between the national level Environmental Quality Index (EQI) and YOCRC in the US. Methods: We used the SEER database to select the CRC patients diagnosed between 2010-2016. YOCRC was defined based on age at diagnosis < 50 years. EQI (2005-2010) is a measure of county-level cumulative environmental exposures that includes 5 domains: sociodemographic, built, air, land, and water. A higher value represents a lower environmental quality. We distributed the total EQI and each EQI domain into five quintiles. Multivariable logistic regression analysis was used to assess the relationship between YOCRC and quintiles (upper-most vs. lowest) of EQI after adjusting by race (White, Black, and Others), gender, and stage at diagnosis. The age-adjusted incidence rate was also calculated using the SEER*Stat, and correlation efficiency was estimated between EQI domains and incidence rate. Results: A total of 261,417 CRC patients were included; 11% were YOCRC. In the adjusted multivariable analysis, poor built EQI (OR 1.15 [1.11-1.20]) and water EQI (OR 1.08 [1.03-1.12]) were more likely to be associated with YOCRC. Poor built EQI was more strongly associated with Black YOCRC (OR 1.21 [1.09-1.35]) as compared to White YOCRC (OR 1.14 [1.09-1.19]). Poor sociodemographic EQI was more strongly associated with Others (OR 1.47 [1.25-1.72]) compared to Black YOCRC (OR 1.14 [1.03-1.25]). In addition, poor built EQI (OR 1.19 [1.12-1.27]) and water EQI (OR 1.12 [1.05-1.19]) were more strongly associated with the metastatic disease among YOCRC patients. However, the total poor EQI was not associated with YOCRC (OR 0.99 [0.95-1.03]). On incidence analysis, there was a positive correlation between the incidence rate of YOCRC and sociodemographic EQI (rho=0.49, p<0.001), air EQI (rho=0.30, p<0.001), and land EQI (rho=0.18, p<0.001). Conclusions: This study evaluated a population-based ecological approach and showed that YOCRC was associated with lower environmental quality, including built and water domains. EQI domains were also associated with different racial groups among YOCRC. [Table: see text]

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Barot, Shimoli V., Naseer Sangwan, Kanika G. Nair, Stephanie Schmit, Shao Xiang, Suneel Deepak Kamath, David Liska, and Alok A. Khorana. "Tumor microbiome variation in young versus average onset colorectal cancer." Journal of Clinical Oncology 40, no. 4_suppl (February 1, 2022): 144. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.144.

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144 Background: The incidence of young onset colorectal cancer (yoCRC) is rising at alarming rates. The gut microbiome may be a factor accounting for the increase. We analyzed differences in the intratumoral microbiome of yoCRC vs average onset CRC (aoCRC) and its clinical impact. Methods: We identified 314 histologically confirmed cases of stage I-IV CRC that underwent surgical resection at our institution from 2000-2020, diagnosed <50 years of age for yoCRC and >60 years for aoCRC, who consented to a prospective biorepository. 36 cases were excluded due to nonmalignant, non-adenocarcinoma or metastatic site specimens. Fresh frozen tissue from the primary tumor with paired adjacent nonmalignant tissue specimens were analyzed. 16S rDNA was isolated and sequence reads were assigned to genus level amplicon sequence variants in DADA2 and analyzed for alpha and beta diversity using Phyloseq. Statistical tests included analysis of variance (ANOVA), permutational multivariate analysis (PERMANOVA), linear regression, and Wilcoxon test. Differential abundance and correlation analysis were adjusted for sex and ethnicity as confounding factors. Correlation analysis was adjusted with Benjamini Hochberg correction. Clinical differences were analyzed using Fisher's exact test. Results: Of the cohort of 278 patients, 137 had yoCRC (median age 43 years, range 16-49) and 141 had aoCRC (median age 73 years, range 61-95). yoCRC patients were more likely to have stage III or IV disease at presentation (29% vs 14%, p =0.002; 29% vs 18%, p =0.024 respectively), left sided tumors (74% vs 58%, p =0.003) and receive neoadjuvant therapy (29% vs 15%, p =0.004). yoCRC had significantly higher tumor microbial alpha diversity than aoCRC ( p <2.22e−16, Wilcoxon rank-sum test). Beta diversity analysis demonstrated significantly different diversity of genera between the groups (R2=0.12, p =0.001, PERMANOVA). The prevalent taxa identified in both groups were Lactobacillus, Bacillus and Listeria. Differential abundance analysis (ANOVA, p <0.05) revealed a significant variation of intratumoral microbiome (Table). Correlation analysis revealed an association of longer overall survival (OS) with the presence of Akkermansia in yoCRC (R2 =0.36, p <0.001), but not in aoCRC. Conclusions: We found significant differences between the intratumoral microbiome of yoCRC and aoCRC. In particular, Akkermansia, considered a healthy gut microbe, was found in greater relative abundance in yoCRC and correlated with improved OS. Further studies are warranted to understand the nature of association of these microbes with the development of and outcomes in yoCRC. [Table: see text]

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Lee, Jieun, In-Ho Kim, Jin Su Kim, Sang Woo Kim, Jun Gi Kim, Seung Tack Oh, Won Kyung Kang, and Myung Ah Lee. "Different clinical characteristics in sporadic young-age onset colorectal cancer." Medicine 95, no. 37 (September 2016): e4840. http://dx.doi.org/10.1097/md.0000000000004840.

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Murphy, Caitlin C., Jennifer L. Lund, and Robert S. Sandler. "Young-Onset Colorectal Cancer: Earlier Diagnoses or Increasing Disease Burden?" Gastroenterology 152, no. 8 (June 2017): 1809–12. http://dx.doi.org/10.1053/j.gastro.2017.04.030.

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You, Y. Nancy. "Young-Onset Colorectal Cancer: Is It Time to Pay Attention?" Archives of Internal Medicine 172, no. 3 (February 13, 2012): 287. http://dx.doi.org/10.1001/archinternmed.2011.602.

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Lamprell, Klay, Diana Fajardo Pulido, Yvonne Tran, Bróna Nic Giolla Easpaig, Winston Liauw, Gaston Arnolda, and Jeffrey Braithwaite. "Personal Accounts of Young-Onset Colorectal Cancer Organized as Patient-Reported Data: Protocol for a Mixed Methods Study." JMIR Research Protocols 10, no. 2 (February 26, 2021): e25056. http://dx.doi.org/10.2196/25056.

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Background Young-onset colorectal cancer is a contemporary issue in need of substantial research input. The incidence of colorectal cancer in adults younger than 50 years is rising in contrast to the decreasing incidence of this cancer in older adults. People with young-onset colorectal cancer may be at that stage of life in which they are establishing their careers, building relationships with long-term partners, raising children, and assembling a financial base for the future. A qualitative study designed to facilitate triangulation with extant quantitative patient-reported data would contribute the first comprehensive resource for understanding how this distinct patient population experiences health services and the outcomes of care throughout the patient pathway. Objective The aim of this study was to undertake a mixed-methods study of qualitative patient-reported data on young-onset colorectal cancer experiences and outcomes. Methods This is a study of web-based unsolicited patient stories recounting experiences of health services and clinical outcomes related to young-onset colorectal cancer. Personal Recollections Organized as Data (PROD) is a novel methodology for understanding patients’ health experiences in order to improve care. PROD pivots qualitative data collection and analysis around the validated domains and dimensions measured in patient-reported outcome and patient-reported experience questionnaires. PROD involves 4 processes: (1) classifying attributes of the contributing patients, their disease states, their routes to diagnosis, and the clinical features of their treatment and posttreatment; (2) coding texts into the patient-reported experience and patient-reported outcome domains and dimensions, defined a priori, according to phases of the patient pathway; (3) thematic analysis of content within and across each domain; and (4) quantitative text analysis of the narrative content. Results Relevant patient stories have been identified, and permission has been obtained for use of the texts in primary research. The approval for this study was granted by the Macquarie University Human Research Ethics Committee in June 2020. The analytical framework was established in September 2020, and data collection commenced in October 2020. We will complete the analysis in March 2021 and we aim to publish the results in mid-2021. Conclusions The findings of this study will identify areas for improvement in the PROD methodology and inform the development of a large-scale study of young-onset colorectal cancer patient narratives. We believe that this will be the first qualitative study to identify and describe the patient pathway from symptom self-identification to help-seeking through to diagnosis, treatment, and to survivorship or palliation for people with young-onset colorectal cancer. International Registered Report Identifier (IRRID) DERR1-10.2196/25056

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Comandasu, Meda Laura, Emel Suliman, Octavia Rusu, C. Savlovschi, and S. Oprescu. "EARLY-ONSET COLORECTAL CANCER: CLINICO-PATHOLOGICAL IMPLICATIONS (EOCRC)." Romanian Medical Journal 62, no. 2 (June 30, 2015): 189–94. http://dx.doi.org/10.37897/rmj.2015.2.18.

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Objective. The purpose of this study is to analyse histopathological and clinical characteristics of EOCRC. Colorectal cancer was formerly considered as a disease of senescent age; in the last years, it is a noticeable trend of growing incidence among young people (aged between 20 and 45 years). Few of newly diagnosed cases are inherited and most of them are sporadic. Material and method. The authors studied retrospectively a series of 33 cases of early onset colorectal cancer, 17 men and 16 women, with ages below 45 years, admitted between January 2009 and January 2015 in II and IV Surgical Wards of Emergency University Hospital Bucharest. Results. Colorectal cancer in young adults tends to be an aggressive disease with dominant distal location (68.5% of all cases), mostly adenocarcinomas (96.6%) with moderate to poorly differentiated types (51.4% G2 and G3), diagnosed in advanced stages (57.6% stages III and IV), with high frequency of complications (33% presented with peritoneal carcinomatosis and 9% died during hospitalization). Conclusions. EOCRC is a heterogenous group regarding etiopathogeny, localization and histopathological features of the tumor, with aggresive histopathological types, diagnosed in advanced stages. It may be necessary to elaborate new screening protocols for colorectal cancer in young adults and to fi nd clinical and biological markers that are indicating high-risk patients.

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Fangman, Benjamin D., Suleyman Y. Goksu, Nivan Chowattukunnel, Muhammad S. Beg, Nina N. Sanford, Aravind Sanjeevaiah, John Cox, et al. "Disparities in Characteristics, Access to Care, and Oncologic Outcomes in Young-Onset Colorectal Cancer at a Safety-Net Hospital." JCO Oncology Practice 17, no. 5 (May 2021): e614-e622. http://dx.doi.org/10.1200/op.20.00777.

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PURPOSE: Young-onset colorectal cancer is an emerging cause of significant morbidity and mortality globally. Despite this, limited data exist regarding clinical characteristics and outcomes, particularly in safety-net populations where access to care is limited. We aimed to study disparities in clinical characteristics and outcomes in patients with young-onset colorectal cancer in the safety-net setting. METHODS: We performed a retrospective review of patients < 50 years old diagnosed and/or treated for colorectal cancer between 2001 and 2017 at a safety-net hospital. Kaplan-Meier and Cox regression models were constructed to compare overall survival (OS), progression-free survival (PFS), and relapse-free survival (RFS) by race and ethnicity, stratifying for relevant clinical and pathologic factors. RESULTS: A total of 395 young-onset patients diagnosed at a safety-net hospital were identified and 270 were included in the analysis (49.6% Hispanic, 25.9% non-Hispanic Black, 20.0% non-Hispanic White, and 4.4% other). Non-Hispanic White race was independently associated with worse OS (hazzard ratio [HR], 0.53; 95% CI, 0.29 to 0.97), as were lack of insurance, higher clinical stage, and mismatch repair proficiency. There was no significant difference seen in PFS or RFS between racial and ethnic groups. CONCLUSION: Non-Hispanic White race or ethnicity was found to be independently associated with worse OS in a safety-net population of patients with young-onset colorectal cancer. Other independent predictors of worse OS include higher stage, lack of insurance, and mismatch repair proficiency.

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Zheng, Xi, Heather Yeo, Doron Betel, and Manish Shah. "Young-Onset Colorectal Cancer: A More Aggressive Disease on the Rise: ACG Colorectal Cancer Prevention Award." American Journal of Gastroenterology 109 (October 2014): S199—S200. http://dx.doi.org/10.14309/00000434-201410002-00688.

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Porter, Laura Diane, Ronit Yarden, and Kim Lynn Newcomer. "Young-onset colorectal: Emotional and psychosocial effects on patients, survivors, and caregivers." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3592. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3592.

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3592 Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. Young-onset colorectal cancer refers to individuals diagnosed under the age of 50. In recent years, the incidence has increased by 2.2% annually in individuals younger than 50 years, and 1% in individuals 50-64, in contrast to a 3.3% decrease in adults 65 years and older. The Colorectal Cancer Alliance launched the Never Too Young Survey and the Caregiver Survey to assess and better understand the unmet needs of the young-onset population and their caregivers. Methods: A cross-sectional study, conducted in the form of an online survey, was launched to better understand the experiences around YO-CRC patients and caregivers. YO-CRC patients and survivors (N = 885) and caregivers (N = 204) completed an online questionnaire that was based on established instruments including PROMIS, EORTC-QOL-30, and EORTC-CR-29. The final survey instrument and study plan were reviewed and approved by the Aspire Inc. Institutional Review Board. Results: Nearly 75% of patients/survivors shared that they have been concerned about their mental health, and 64% responded that they have needed help for their depression. Further, 67% of caregivers surveyed responded that they were also concerned about their mental health, and 68% responded that they needed help with their depression. Seventy-one percent of caregivers often felt sadness, and 30% indicated that they had lost hope. Emotional exhaustion was reported by 77% of caregivers, whether they were providing round-the-clock care or caregiving from a distance. The effect was more pronounced in the patient/survivor cohort, with 95% indicating that emotional exhaustion impacted their lives. As a result, 71% of caregivers and 29% of patients/survivors indicated that they had withdrawn from other people. These results indicate the emotional toll that colorectal cancer has on patients/survivors and caregivers and their need for further resources. Conclusions: The Colorectal Cancer Alliance is committed to meeting these needs and providing resources that support patients, survivors and caregivers. Information and services may assist the caregiver in helping the patient make decisions, including shifting roles and routines in response to changing demands of YO-CRC. Further studies should investigate psychological well-being and support strategies.

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Danial, Daneshvar, El Douaihy Youssef, Bayat Mokhtari Maryam, Abureesh Mohammad, Bayat Mokhtari Moein, and Deeb Liliane. "Risk Factors of Young-Onset Colorectal Cancer: Analysis of a Large Population-Based Registry." Canadian Journal of Gastroenterology and Hepatology 2022 (February 16, 2022): 1–8. http://dx.doi.org/10.1155/2022/3582443.

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Background. As the third most common type of cancer in the United States, colorectal cancer (CRC) was previously thought to be rare in young populations. Despite a decrease in the overall incidence of CRC, the rate of new cases under 50 years old has been continuously increasing. Aim. The purpose of our study was to analyze risk factors of young-onset CRC. Methods. Commercially available software platform, Explorys, was used to extract data from a collective healthcare database electronically. Results. In this database, 13,800 young adults (age 20–50) were diagnosed with primary colorectal malignancy. Compared to subjects with a previous family history of CRC who had an odds ratio of 17.78, those diagnosed with primary malignant neoplasm of breast and inflammatory bowel disease (ulcerative colitis and Crohn’s) had odds ratios of 16.94, 4.4, and 3.7 for young-onset CRC, respectively. Patients with a history of alcohol abuse, smoking, obesity, diabetes mellitus, and hyperlipidemia had higher chances of developing young-onset CRC. In addition, the odds of CRC were lower in Hispanic ethnicity in comparison to Caucasians (OR: 0.54), with no statically significant differences between Caucasian, African American, and Asian populations. Conclusion. Currently, this is an expansive study investigating the risk factors for early-onset CRC. The analysis showed factors such as family and individual history of IBD to have high association with early onset. Notably, an individual history of breast malignancy was strongly associated with early-onset CRC.

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Hayes, Richard B. "Abstract IA012: Risk factors for early-onset colorectal cancer." Cancer Research 82, no. 23_Supplement_1 (December 1, 2022): IA012. http://dx.doi.org/10.1158/1538-7445.crc22-ia012.

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Abstract Colorectal cancer (CRC) incidence has been declining in the U.S. overall; however, the incidence of CRC in individuals less than 50 years of age (early-onset disease) has been increasing over the last several decades in the U.S. and elsewhere. Furthermore, cancers diagnosed in people less than 50 years of age tend to be characterized by advanced stage and greater propensity for recurrence, increasing the urgency of this emerging public health problem. Responding to the rapid rise in early-onset CRC, some CRC screening guidelines have changed to lower the screening age from 50 to 45, for average risk individuals. Our purpose was to identify genetic, environmental and lifestyle risk factors for early-onset CRC which could be used in predictive modelling to identify the younger individuals who would most benefit from screening. This research, which included more than 3,500 early-onset CRC and 3,500 comparison controls, serves to comprehensively assess genetic, environmental and lifestyle risks in early-onset CRC, as well as to develop a risk prediction tool specifically for this age group. We found that a polygenic risk score is associated with early-onset CRC, particularly for those without a family history of CRC. Several known CRC environmental and lifestyle risk factors are also linked with early-onset disease. In summary, the absolute risk for CRC in young people is low; however, genetic, environmental and lifestyle information provides initial stratification into low and high-risk groups. These findings may contribute to the identification of individuals susceptible to early-onset CRC for tailored early detection or other preventive interventions. Citation Format: Richard B. Hayes. Risk factors for early-onset colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA012.

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Yılmazlar, Tuncay, Abdullah Zorluoğlu, Halil Özgüç, Nusret Korun, Hakan Duman, Ekrem Kaya, and Ayhan Kızıl. "Colorectal Cancer in Young Adults." Tumori Journal 81, no. 4 (July 1995): 230–33. http://dx.doi.org/10.1177/030089169508100402.

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The study was carried out to promote a greater awareness of the potential for colorectal cancer in young adults under 40 years of age. During the 8 years between 1986 and 1993, 237 patients with adenocarcinoma of the colon and rectum were operated at the Uludağ University Hospital. Of these 237 cases, 46 patients under 40 years old were reviewed retrospectively. They accounted for 19.4% of the total number of patients with carcinoma of the colon and rectum operated during the same period. Rectal bleeding was the most common presenting symptom. The mean duration of time from the onset of symptoms to diagnosis was 5.8 months. The rectosigmoid area was the most frequently involved site (80%). Seventy-six percent of the patients had Dukes’ stage C or D tumors. Forty-eight percent of the tumors were either poorly differentiated or mucinous. The cumulative survival rate at 5 years was 43.4%. Patients under 40 years old with carcinoma of the colon and rectum are usually symptomatic and have advanced disease at the time of presentation. Although colorectal cancer is usually a disease of older patients it is becoming more common in younger populations.

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Wong, Sunny H., and Joseph JY Sung. "Looking for Young-onset Colorectal Cancer – It is Coming to Asia." Annals of the Academy of Medicine, Singapore 49, no. 11 (November 30, 2020): 836–37. http://dx.doi.org/10.47102/annals-acadmedsg.2020549.

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38

Dozois, Eric J., Lisa A. Boardman, Weerapat Suwanthanma, Paul J. Limburg, Robert R. Cima, Julie L. Bakken, Robert A. Vierkant, Jeremiah A. Aakre, and David W. Larson. "Young-Onset Colorectal Cancer in Patients With No Known Genetic Predisposition." Medicine 87, no. 5 (September 2008): 259–63. http://dx.doi.org/10.1097/md.0b013e3181881354.

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39

Ying, Daniel Wang, David R. Risser, Patricia Thompson, Neda Zarrin-Khameh, Melissa Bondy, and Benjamin Leon Musher. "Rising incidence of young-onset colorectal cancer in Texas, 1995-2010." Journal of Clinical Oncology 32, no. 15_suppl (May 20, 2014): 1587. http://dx.doi.org/10.1200/jco.2014.32.15_suppl.1587.

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40

Murphy, Caitlin C., Amit G. Singal, John A. Baron, and Robert S. Sandler. "Decrease in Incidence of Young-Onset Colorectal Cancer Before Recent Increase." Gastroenterology 155, no. 6 (December 2018): 1716–19. http://dx.doi.org/10.1053/j.gastro.2018.07.045.

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41

Dharwadkar, Pooja, Garrett Greenan, Amit Singal, and Caitlin Murphy. "Young versus Older-Onset Colorectal Cancer in a Safety Net Hospital." American Journal of Gastroenterology 113, Supplement (October 2018): S121—S122. http://dx.doi.org/10.14309/00000434-201810001-00206.

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42

Goyal, Hemant, Rupak Desai, Upenkumar Patel, Wardah Siddiq, and Rajiv Chhabra. "Young-Onset Colorectal Cancer Related Hospitalizations: It’s Time to Pay Attention." American Journal of Gastroenterology 113, Supplement (October 2018): S142—S143. http://dx.doi.org/10.14309/00000434-201810001-00247.

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43

Kessels, Koen, Herma H. Fidder, Nicolette L. de Groot, Tom G. Letteboer, Robin Timmer, Thijs van Dalen, Esther C. Consten, G. Johan A. Offerhaus, and Peter D. Siersema. "Adherence to Microsatellite Instability Testing in Young-Onset Colorectal Cancer Patients." Diseases of the Colon & Rectum 56, no. 7 (July 2013): 825–33. http://dx.doi.org/10.1097/dcr.0b013e31828b6617.

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44

Boardman, Lisa A., Ruth A. Johnson, Gloria M. Petersen, Ann L. Oberg, Brian F. Kabat, Joshua P. Slusser, Liang Wang, et al. "Higher Frequency of Diploidy in Young-Onset Microsatellite-Stable Colorectal Cancer." Clinical Cancer Research 13, no. 8 (April 15, 2007): 2323–28. http://dx.doi.org/10.1158/1078-0432.ccr-06-2739.

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45

Sutton, Elie, Geoffrey Bellini, Dave Lee, Linda Njoh, and Richard L. Whelan. "Tu1812 An Update on Young-Onset Colorectal Cancer, an NCDB Analysis." Gastroenterology 150, no. 4 (April 2016): S1260. http://dx.doi.org/10.1016/s0016-5085(16)34258-5.

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46

Bonnamy, James. "Holding Multiple Identities: a Personal Narrative of Young Onset Colorectal Cancer." Journal of Cancer Education 35, no. 6 (April 8, 2020): 1261–66. http://dx.doi.org/10.1007/s13187-020-01740-2.

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You, Y. Nancy, Kyle Chang, Ken Chen, Amir Mehdizadeh, Amanda Cuddy, Christopher Hanyoung Lieu, Kenna Rael Shaw, Eduardo Vilar Sanchez, and Cathy Eng. "Somatic mutations in young-onset colorectal cancer unrelated to hereditary syndromes: A comparative study using high-depth targeted exome sequencing." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 623. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.623.

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623 Background: Colorectal cancer (CRC) is being increasingly diagnosed among young adults, but known hereditary syndromes do not account for the majority of these cases. Young patients often present with metastatic disease and exhibit aggressive clinical courses. We aimed to elucidate the potentially unique biology of young-onset CRC. Methods: Patients diagnosed with metastatic CRC prior to age 40 without a known predisposing syndrome (young-onset) were compared to similar patients diagnosed after age 60 (later-onset). Primary and/or metastatic tumor tissues from 19 young- and 51 later-onset patients underwent targeted exome sequencing on a panel of 200 genes using Illumina HiSeq2000 performed by the Institute of Personalized Cancer Therapeutics of MD Anderson Cancer Center. Sequencing was to an average depth of 800x; single nucleotide variations (SNVs) were called according to in-house algorithms. Results: The median age of patients with young-onset CRCs was 34 years (interquartile range: 31-37), while that of later-onset CRCs was 66 years (IQR: 62- 72). The primary CRC was in the rectum in 30% of the young- vs. 16% of the later-onset cases. The overall mutational rate as measured by the number of SNVs per patient (median: 7 vs. 9) did not differ significantly between the groups. However, the median allelic frequency of SNVs was higher in the young-onset group (0.34 vs. 0.17%), suggesting differing patterns of tumor heterogeneity. Genes known to be associated with CRC carcinogenesis were mutated at different proportions (Table); SMAD4, mismatch repair genes (MSH6, MLH1, MSH2), ARID1A, IGF1R and KITappear to be more frequently mutated among the young. Conclusions: This exploratory study suggests that the somatic mutation profiles are distinct between young- vs. later-onset CRCs. More in-depth analysis of the genomic landscape of young-onset CRCs may reveal distinct and novel therapeutic avenues. [Table: see text]

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Sandhu, Gurprataap Singh, Rebekah Anders, Amy Walde, Alexis Diane Leal, Gentry Teng King, Stephen Leong, S. Lindsey Davis, et al. "High incidence of advanced stage cancer and prolonged rectal bleeding history before diagnosis in young-onset patients with colorectal cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 3576. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.3576.

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3576 Background: In contrast to the older population, the incidence of colorectal cancer (CRC) in younger patients (aged < 50 years) has been increasing in the last three decades. Younger patients tend to present with more advanced disease, thought to be in part related to lack of routine screening colonoscopies. The goal of this study was to examine characteristics of young-onset CRC and potentially identify factors that may aid in earlier diagnosis and treatment. Methods: We collected data for patients available through the University of Colorado Cancer Center Cancer Registry. Inclusion criteria included: 1) Diagnosis of colon or rectal cancer between the years 2012-2018 and 2) age at diagnosis of less than 50 years. Pertinent data including baseline characteristics, clinical presentation, family history, pathology, molecular testing, staging, and treatment were collected. Results: 211 patients with young-onset CRC were available for review. Mean age at diagnosis was 42.4 years and 55.5% were males. A total of 42.1% had rectal cancer and a majority of the colon cancer diagnoses had left-sided tumors (66%). Regarding clinical presentation, 52.2% presented with rectal bleeding prior to diagnosis. Of those who presented with rectal bleeding, the average time from the onset of bleeding to diagnosis was 271.17 days. 42.9% of young-onset CRC were stage IV at the time of initial diagnosis. Evaluation of the pathology specimens showed that 89.6% were adenocarcinomas and 63.5% were grade 2 or higher. At diagnosis, the mean BMI was 26.6 and the mean CEA was 135.5. A total of 72.5% of young-onset patients had a positive family history of any cancer. KRAS or NRAS mutations were present in 49.6% of patients, BRAF V600E mutations were present in 3.8%, and 10.8% were MSI-H. Conclusions: Prolonged rectal bleeding history prior to diagnosis was noted in a significant proportion of young-onset patients with colorectal cancer. Patients and primary care physicians should be made aware of this finding in order to facilitate timely referral for colonoscopy which may lead to earlier diagnosis, less advanced disease at diagnosis, and improved outcomes.

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Magnani, Giulia, Daniela Furlan, Nora Sahnane, Luca Reggiani Bonetti, Federica Domati, and Monica Pedroni. "Molecular Features and Methylation Status in Early Onset (≤40 Years) Colorectal Cancer: A Population Based, Case-Control Study." Gastroenterology Research and Practice 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/132190.

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Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression,KRASandBRAFmutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair,APCandMUTYHgenes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%).KRASmutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02). Finally both of the two groups were highly methylated inESR1,GATA5, andWT1genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation ofESR1,GATA5, andWT1genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

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Chang, George J., Y. Nancy Y. You, Christy A. Russell, Marni B. Tierno, Michelle Turner, John P. Bennett, Anna Lau, and Howard S. Hochster. "Young-Onset Colon Cancer and Recurrence Risk by Gene Expression." JNCI: Journal of the National Cancer Institute 112, no. 11 (February 5, 2020): 1170–73. http://dx.doi.org/10.1093/jnci/djaa019.

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Abstract The incidence and mortality from colorectal cancer in younger adults (younger than 55 years) is increasing. We reviewed the complete database of a gene-expression test, Oncotype DX Colon Recurrence Score test, to determine age-related differences in recurrence score (RS) and single-gene results (7 cancer-related of the 12-gene assay). We included 20 478 stage II and III A and B colon cancer patients submitted to Genomic Health. RS results were grouped by low-, intermediate-, and high-risk groups. Single-gene scores were described using median and interquartile range. Of all patients 72.5% and 72.6% of those younger than 40 years had low-risk RS. Comparing older with younger patients, RS or single-gene expression did not differ by age group or stage. Young-onset colon cancer does not differ by expression of the RS component genes. Most patients with stage II and III colon cancer have low-risk disease as measured by the 12-gene assay, regardless of age.

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