Colorectal cancer of the young displays distinct features of aggressive tumor biology: A single-center cohort study

Mueller, Matteo; Schneider, Marcel; Deplazes, Barla; Cabalzar-Wondberg, Daniela; Rickenbacher, Andreas; Turina, Matthias

doi:10.4240/wjgs.v13.i2.164

Cited by 11 publications

(10 citation statements)

References 46 publications

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“…The young patient population was defined as subjects under 50 years of age, agreeing with previous studies. 15 Pathological specimens of each patient were examined under the microscope by two independent pathologists who recorded the histopathology characteristics of: pathological tumour staging, histological subtypes, growth pattern, tumour grade, LVI, and PNI. We evaluated the number of dissected LNs in agreement with other studies and WHO guidelines, with a minimum of 12 LNs taken for each case.…”

Section: Methodsmentioning

confidence: 99%

Analysing 11 years of incidence trends, clinicopathological characteristics, and forecasts of colorectal cancer in young and old patients: a retrospective cross-sectional study in an Indonesian national referral hospital

et al. 2022

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ObjectiveTo obtain annual incidence trends, understand clinicopathological characteristics, and forecast the future burden of colorectal cancer (CRC) in Indonesia.Design11-year retrospective cross-sectional study.SettingA national referral hospital in Jakarta, Indonesia.ParticipantsData from 1584 eligible cases were recorded for trends and forecasting analyses; 433 samples were analysed to determine clinicopathological differences between young (<50 years) and old (≥50 years) patients.MethodsTrend analyses were done using Joinpoint software, expressed in annual percentage change (APC), and a regression analysis was executed to generate a forecasting model. Patients’ characteristics were compared using χ2 or non-parametric tests.Main outcomesAnalysis of trends, forecasting model, and clinicopathological features between the age groups.ResultsA significant increase in APC was observed among old patients (+2.38%) for CRC cases. Colon cancer increased remarkably (+9.24%) among young patients; rectal cancer trends were either stable or declining. The trend for right-sided CRC increased in the general population (+6.52%) and old patients (+6.57%), while the trend for left-sided CRC was stable. These cases are expected to be a significant health burden within the next 10 years. Patients had a mean age of 53.17±13.94, 38.1% were young, and the sex ratio was 1.21. Prominent characteristics were left-sided CRC, tumour size ≥5 cm, exophytic growth, adenocarcinoma, histologically low grade, pT3, pN0, inadequately dissected lymph nodes (LNs), LN ratio <0.05, no distant metastasis, early-stage cancer, no lymphovascular invasion, and no perineural invasion (PNI). Distinct features between young and old patients were found in the histological subtype, number of dissected LN, and PNI of the tumour.ConclusionsEpidemiological trends and forecasting analyses of CRC cases in Indonesian patients showed an enormous increase in colon cancer in young patients, a particularly concerning trend. Additionally, young patients exhibited particular clinicopathological characteristics that contributed to disease severity.

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Section: Methodsmentioning

confidence: 99%

Analysing 11 years of incidence trends, clinicopathological characteristics, and forecasts of colorectal cancer in young and old patients: a retrospective cross-sectional study in an Indonesian national referral hospital

et al. 2022

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“…Two large‐scale comparative studies of the SEER (1334 patients aged 20–40 years versus 46 457 patients aged 60–80 years) and the North American National Cancer Database (64 068 patients <50 years versus 524 801 patients aged >50 years) demonstrated poorer differentiation and increased mucinous and signet‐ring tumour morphology in their younger cohorts 28,29 . A smaller‐scale single‐institution study found higher proportions of locally advanced tumours invading adjacent structures (pT4) and lymph node metastases with an overall higher mean lymph node ratio in EOCRC versus LOCRC 30 . Moreover, Vuik et al 31 .…”

Section: Pathological Features and Molecular Profiles Of Eocrcmentioning

confidence: 99%

“…28,29 A smaller-scale single-institution study found higher proportions of locally advanced tumours invading adjacent structures (pT4) and lymph node metastases with an overall higher mean lymph node ratio in EOCRC versus LOCRC. 30 Moreover, Vuik et al 31 established that within their EOCRC cohort exclusively, an inverse relationship existed between age and the presence of adverse pathological features; whereby being in a younger age group (20-29 versus 30-39 versus 40-49 years) was associated with an increased presence of signet-ring cells, poorly differentiated tumours, and lymph node involvement.…”

Section: Pathological Features and Molecular Profiles Of Eocrcmentioning

confidence: 99%

Early‐onset colorectal cancer: why it should be high on our list of differentials

Garrett

Steffens

Solomon

et al. 2022

ANZ Journal of Surgery

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Background: Early-onset colorectal cancer (EOCRC) (<50 years) incidence has increased in Australia and worldwide. However, the diagnosis of EOCRC is often delayed. Recent research has discovered some differences from later-onset colorectal cancer (LOCRC) (>50 years). An awareness of the unique features of EOCRC is crucial to reduce time from symptom onset to diagnosis. Methods: A literature search was conducted on electronic databases (MEDLINE, EMBASE and Cochrane Library) using the search terms "early onset colorectal cancer" or "young onset colorectal cancer." Results: The American Cancer Society has reduced the colorectal cancer screening initiation age to 45 for average-risk adults whilst screening programmes in the United Kingdom and Australia remain unchanged with initiation at 60 and 50, respectively. Exposures resulting in dysbiosis (obesity, westernised diet, alcohol, antibiotic and sugar-sweetened beverage consumption) have been linked with increased EOCRC risk. EOCRC is often leftsided presenting with rectal bleeding, altered bowel habit and constitutional symptoms. EOCRC is more commonly sporadic than hereditary, harbouring different genetic mutations than LOCRC. Comparative survival outcomes of EOCRC and LOCRC are conflicting with studies suggesting either better or poorer survival. Young patients better tolerate treatmentrelated toxicities, which may account for their improved survival despite comparatively advanced stages and poorer histopathological features at diagnosis. Conclusion: Current EOCRC literature is limited by American-focused datasets and heterogenous EOCRC definitions and study designs (the greatest strength of evidence exists for EOCRC risk factor studies comprised of large retrospective cohorts). There is minimal research into the quality of life and surgical outcomes of EOCRC patients, and this area warrants further investigation. The incidence of EOCRCScreening, surveillance, and treatment advances over recent years have decreased the general incidence and mortality rates of CRC in high-income countries. In contrast, the incidence of EOCRC has alarmingly increased in 19 (mainly European and Western) countries, with reports suggesting that EOCRC accounts for 11% and 10% of all male and female CRCs, respectively. 1,2 Whilst there are

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“…Germline mutations in additional high and moderate penetrance cancer genes such as BRCA1, CDH1, and MUTYH, have also been associated with increased risk for the developing colorectal neoplasia (Ma et al, 2018). Recent studies have demonstrated that germline variants in various cancer predisposition genes have been identified in 1 out of 10 adults and children diagnosed with advanced cancer types, as well as those with colorectal (Mueller et al, 2021), pancreatic (Gentiluomo et al, 2020), and metastatic prostate (Giri et aleng, 2019) cancers. The impact of an individual germline variant for clinical decision-making depends on the specific characteristics of the variant (Bertelsen et al, 2019), which classify whether the variant is pathogenic/likely pathogenic (P/LP), or whether it is known and/or it is likely to affect the function of its gene.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer

Xie

Chen

et al. 2022

Front. Genet.

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Background: Bowel cancer is the third-most common cancer and the second leading cause of cancer-related death worldwide. Bowel cancer has a substantial hereditary component; however, additional hereditary risk factors involved in bowel cancer pathogenesis have not been systematically defined.Materials and Methods: A total of 573 patients with bowel cancer were enrolled in the present study, of whom 93.72% had colorectal cancer (CRC). Germline mutations were integrated with somatic mutation information via utilizing target next-generation sequencing.Results: Pathogenic/Likely Pathogenic (P/LP) germline alterations were identified in 47 (8.2%) patients with bowel cancer and the ratio of the number of these patients with family history was significantly higher in the P/LP group than that noted in the non-pathogenic (Non-P) group. Certain rare germline alterations were noted, such as those noted in the following genes: FANCD2, CDH1, and FLCN. A total of 32 patients (68.1%) had germline alterations in the DNA-damage repair (DDR) genes and homologous recombination (HR) accounted for the highest proportion of this subgroup. By comparing 573 patients with bowel cancer with reference controls (China_MAPs database), significant associations (p < 0.01) were observed between the incidence of bowel cancer and the presence of mutations in APC, ATM, MLH1, FANCD2, MSH3, MSH6, PMS1, and RAD51D. Somatic gene differential analysis revealed a marked difference in 18 genes and a significant difference was also noted in tumor mutation burden (TMB) between germline mutation carriers and non-germline mutation subjects (p < 0.001). In addition, TMB in DDR mutation groups indicated a dramatic difference compared with the non-DDR mutation group (p < 0.01). However, no statistically significant differences in TMB were noted among detailed DDR pathways for patients with bowel cancer, irrespective of the presence of germline mutations. Moreover, a significantly higher level (p < 0.0001) of mutation count was observed in the DDR group from The Cancer Genome Atlas (TCGA) database and the DDR and non-DDR alteration groups displayed various immune profiles.Conclusion: Chinese patients with bowel cancer exhibited a distinct spectrum of germline variants, with distinct molecular characteristics such as TMB and DDR. Furthermore, the information on somatic mutations obtained from TCGA database indicated that a deeper understanding of the interactions among DDR and immune cells would be useful to further investigate the role of DDR in bowel cancer.

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Colorectal cancer of the young displays distinct features of aggressive tumor biology: A single-center cohort study

Cited by 11 publications

References 46 publications

Analysing 11 years of incidence trends, clinicopathological characteristics, and forecasts of colorectal cancer in young and old patients: a retrospective cross-sectional study in an Indonesian national referral hospital

Analysing 11 years of incidence trends, clinicopathological characteristics, and forecasts of colorectal cancer in young and old patients: a retrospective cross-sectional study in an Indonesian national referral hospital

Early‐onset colorectal cancer: why it should be high on our list of differentials

Prevalence and Spectrum of Predisposition Genes With Germline Mutations Among Chinese Patients With Bowel Cancer

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