scholarly journals Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3817
Author(s):  
Caroline Himbert ◽  
Jane C. Figueiredo ◽  
David Shibata ◽  
Jennifer Ose ◽  
Tengda Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Neoadjuvant Treatment ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Systemic Treatments ◽  
Early Onset Colorectal Cancer

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (<50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

scholarly journals High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer

2021 ◽  
Author(s):  
Jeong Eun Kim ◽  
Jaeyong Choi ◽  
Chang-Ohk Sung ◽  
Yong Sang Hong ◽  
Sun Young Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Large Scale ◽  
Late Onset ◽  
Age Groups ◽  
The Cancer Genome Atlas ◽  
Whole Genome ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Early Onset Colorectal Cancer

AbstractThe global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.

scholarly journals Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

2019 ◽  
Vol 20 (4) ◽  
pp. 968 ◽  
Author(s):  
Edurne Álvaro ◽  
Juana M. Cano ◽  
Juan L. García ◽  
Lorena Brandáriz ◽  
Susana Olmedillas-López ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Age Of Onset ◽  
Late Onset ◽  
Cpg Island ◽  
Low Frequency ◽  
Tumor Location ◽  
Molecular Characteristics ◽  
Braf Mutations ◽  
Rectal Cancers

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.

Risk factors and clinical characteristics of early-onset colorectal cancer vs. late-onset colorectal cancer

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Milena Di Leo ◽  
Raffaella A. Zuppardo ◽  
Marta Puzzono ◽  
Ilaria Ditonno ◽  
Alessandro Mannucci ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Early Onset ◽  
Clinical Characteristics ◽  
Late Onset ◽  
Early Onset Colorectal Cancer

Treatment patterns and survival differ between early-onset and late-onset colorectal cancer patients: the patient outcomes to advance learning network

2019 ◽  
Vol 30 (7) ◽  
pp. 747-755 ◽  
Author(s):  
Andrea N. Burnett-Hartman ◽  
J. David Powers ◽  
Jessica Chubak ◽  
Douglas A. Corley ◽  
Nirupa R. Ghai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Patient Outcomes ◽  
Early Onset ◽  
Late Onset ◽  
Treatment Patterns ◽  
Learning Network ◽  
Colorectal Cancer Patients

scholarly journals Identification of candidate predisposing copy number variants in familial and early-onset colorectal cancer patients

2011 ◽  
Vol 129 (7) ◽  
pp. 1635-1642 ◽  
Author(s):  
Ramprasath Venkatachalam ◽  
Eugène T.P. Verwiel ◽  
Eveline J. Kamping ◽  
Eveline Hoenselaar ◽  
Heike Görgens ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Copy Number ◽  
Copy Number Variants ◽  
Colorectal Cancer Patients ◽  
Early Onset Colorectal Cancer

Use of Molecular Tumor Characteristics to Prioritize Mismatch Repair Gene Testing in Early-Onset Colorectal Cancer

2005 ◽  
Vol 23 (27) ◽  
pp. 6524-6532 ◽  
Author(s):  
Melissa C. Southey ◽  
Mark A. Jenkins ◽  
Leeanne Mead ◽  
Jonathan Whitty ◽  
Melanie Trivett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Protein Expression ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Early Onset ◽  
Amsterdam Criteria ◽  
Colorectal Cancer Patients ◽  
Early Onset Colorectal Cancer ◽  
Mmr Proteins

Purpose The relationships between mismatch repair (MMR) protein expression, microsatellite instability (MSI), family history, and germline MMR gene mutation status have not been studied on a population basis. Methods We studied 131 unselected patients with colorectal cancer diagnosed younger than age 45 years. For the 105 available tumors, MLH1, MSH2, MSH6, and PMS2 protein expression using immunohistochemistry (IHC) and MSI were measured. Germline DNA was screened for hMLH1, hMSH2, hMSH6, and hPMS2 mutations for the following patients: all from families fulfilling the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer (HNPCC); all with tumors that were high MSI, low MSI, or that lacked expression of any MMR protein; and a random sample of 23 with MS-stable tumors expressing all MMR proteins. Results Germline mutations were found in 18 patients (nine hMLH1, four hMSH2, four hMSH6, and one hPMS2); all tumors exhibited loss of MMR protein expression, all but one were high MSI or low MSI, and nine were from a family fulfilling Amsterdam Criteria. Sensitivities of IHC testing, MSI (high or low), and Amsterdam Criteria for MMR gene mutation were 100%, 94%, and 50%, respectively. Corresponding positive predictive values were 69%, 50%, and 75%. Conclusions Tumor IHC analysis of four MMR proteins and MSI testing provide a highly sensitive strategy for identifying MMR gene mutation–carrying, early-onset colorectal cancer patients, half of whom would have been missed using Amsterdam Criteria alone. Tumor-based approaches for triaging early-onset colorectal cancer patients for MMR gene mutation testing, irrespective of family history, appear to be an efficient screening strategy for HNPCC.

Candidate predisposing germline copy number variants in early onset colorectal cancer patients

2016 ◽  
Vol 19 (5) ◽  
pp. 625-632 ◽  
Author(s):  
A. J. Brea-Fernandez ◽  
C. Fernandez-Rozadilla ◽  
M. Alvarez-Barona ◽  
D. Azuara ◽  
M. M. Ginesta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Copy Number ◽  
Copy Number Variants ◽  
Colorectal Cancer Patients ◽  
Early Onset Colorectal Cancer
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