Time to Diagnosis of Early-Onset vs. “Late-Onset” Colorectal Cancer: Is there a difference?

BACKGROUND Colorectal cancer (CRC) incidence and mortality is increasing in persons ˂ 50 years old. Intervals between symptom onset and initial presentation (presentation interval [PI]) and between initial presentation and diagnosis (diagnosis interval [DI]) are not well-quantified. OBJECTIVE Compare PI and DI between early-onset CRC (EOCRC) and persons >50, and identify factors affecting these intervals. METHODS In this retrospective VA-based case-control study, we identified EOCRC cases from an ongoing study and compared them to controls (CRC patients aged ≥ 50 years). We abstracted demographics, clinical features, CRC location and stage, PI, and DI. Mann-Whitney tests compared mean and median PI and DI. RESULTS Advanced stage (III-IV) CRC was more common among the 240 EOCRC patients (mean age: 45.2, 60.8% White) than in the 234 controls (mean age: 63.8, 71.8% White): 55.4% vs 43.5%; P= 0.015. PIs and DIs, respectively, were present for 153(63.8%) and 222(92.5%) of cases and for 74(31.6%) 222(94.9%) of controls. No difference was found between median PI in EOCRC and late-onset CRC patients (42 vs 60 days, P= 0.68). The EOCRC cases had a significantly shorter median DI (41 [IQR = 16-83] vs 71 days [IQR = 32-145], P<0.0001). CONCLUSIONS In this retrospective study, younger patients had more advanced stage CRC at diagnosis than their older counterparts. However, contrary to published data, median time to diagnosis was shorter in those < 50 years. Factors associated with the DI are forthcoming. Candidate factors include race, diagnosis year, presenting symptoms, type of initial provider, CRC stage, and CRC location.

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Su1662 – Time to Diagnosis of Early-Onset Vs. “Late-Onset” Colorectal Cancer: is There a Difference?

Gastroenterology ◽

10.1016/s0016-5085(19)38400-8 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-602

Author(s):

Thomas F. Imperiale ◽

Laura Myers ◽

Kayla L. Chin ◽

Carrie J. Ballard ◽

Jessica Coffing ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Late Onset ◽

Time To Diagnosis

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Tumor characteristics and treatment in early-onset colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.566 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 566-566

Author(s):

Andrea Burnett-Hartman ◽

John D. Powers ◽

Jessica Chubak ◽

Douglas Corley ◽

Nirupa R. Ghai ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Nodes ◽

Systemic Therapy ◽

Early Onset ◽

Late Onset ◽

Patient Characteristics ◽

Left Colon ◽

Tumor Characteristics ◽

Incidence And Mortality ◽

Signet Ring

566 Background: While overall incidence and mortality of colorectal cancer (CRC) has declined, incidence and mortality are increasing in those < 50 years old (early-onset CRC). Our objective was to better understand early-onset CRC by comparing tumor characteristics and initial treatment type between early-onset and normal/late-onset CRC. Methods: We used health system and national tumor registries to identify patients diagnosed with adenocarcinoma of the colon or rectum from 2010-2014 at 6 US integrated health systems in the Patient Outcomes To Advance Learning (PORTAL) network. Tumor registry data included: age at diagnosis, stage, grade, anatomic site, histology, number of lymph nodes examined, and receipt of initial systemic therapy (chemotherapy or immunotherapy). Demographics and other patient characteristics were obtained from the EHR. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset ( < 50 years old) vs. normal/late-onset CRC. Results: There were 1,424 early-onset and 10,810 normal/late onset CRC cases in our analyses. Compared to normal/late onset cases, patients with early-onset CRC were more likely to be Hispanic, obese, never smokers, and to have Charlson comorbidity scores < 3. After adjustment for patient characteristics, compared to normal/late onset CRC, early-onset CRC was associated with more advanced stage disease (OR for stage 4 vs. stage 1 = 2.8, CI: 2.4-3.4), high grade histology (OR for poorly differentiated/undifferentiated vs. well/moderately differentiated = 1.2, CI: 1.1-1.5), signet ring histology (OR for signet ring vs. non-mucinous adenocarcinoma = 1.7, CI: 1.1, 2.6), and rectal (OR for rectum vs. cecum = 2.4, CI: 1.9-2.9) or left colon location (OR for left colon vs. cecum = 2.2, CI: 1.8-2.8). After adjustment for patient and tumor characteristics, early-onset patients were more likely than normal/late onset patients to have > 12 lymph nodes examined (OR = 1.6, CI: 1.4-1.8) and to receive systemic therapy (OR = 2.8, CI: 2.4, 3.4). Conclusions: Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use.

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

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00583-1 ◽

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.

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Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

Molecular Cancer ◽

10.1186/1476-4598-9-100 ◽

2010 ◽

Vol 9 (1) ◽

pp. 100 ◽

Cited By ~ 54

Author(s):

Marianne Berg ◽

Trude H Agesen ◽

Espen Thiis-Evensen ◽

INFAC-study group [infac] ◽

Marianne A Merok ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

High Resolution ◽

Gene Expression Data ◽

Early Onset ◽

Late Onset ◽

Expression Data ◽

Susceptibility Loci ◽

Genome Profiles

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

International Journal of Molecular Sciences ◽

10.3390/ijms20040968 ◽

2019 ◽

Vol 20 (4) ◽

pp. 968 ◽

Cited By ~ 6

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.

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Global Transcriptome Differences Between Early-Onset and Late-Onset Colorectal Cancer

The American Journal of Gastroenterology ◽

10.14309/00000434-201510001-01399 ◽

2015 ◽

Vol 110 ◽

pp. S604-S605

Author(s):

Xi Emily. Zheng ◽

Manish A. Shah ◽

Xiaoping Zou ◽

Levi Waldron

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Late Onset ◽

Global Transcriptome

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Incident Crohn’s Disease as a Risk Factor for Colorectal Cancer in the First 10 Years after Diagnosis: A Nationwide Population-Based Study

Journal of Clinical Medicine ◽

10.3390/jcm10204663 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4663

Author(s):

Hyunil Kim ◽

Ji Hoon Kim ◽

Jung Kuk Lee ◽

Dae Ryong Kang ◽

Su Young Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Early Onset ◽

Late Onset ◽

Age Groups ◽

Population Based ◽

Hazard Ratios ◽

Increased Risk ◽

Cox Proportional Hazard Regression

We investigated the risk of colorectal cancer (CRC) in patients with Crohn’s disease (CD) using the claims data of the Korean National Health Insurance during 2006–2015. The data of 13,739 and 40,495 individuals with and without CD, respectively, were analyzed. Hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression tests. CRC developed in 25 patients (0.18%) and 42 patients (0.1%) of the CD and non-CD groups, respectively. The HR of CRC in the CD group was 2.07 (95% confidence interval (CI), 1.25–3.41). The HRs of CRC among men and women were 2.02 (95% CI 1.06–3.87) and 2.10 (95% CI, 0.96–4.62), respectively. The HRs of CRC in the age groups 0–19, 20–39, 40–59, and ≥60 years were 0.07, 4.86, 2.32, and 0.66, respectively. The HR of patients with late-onset CD (≥40 years) was significantly higher than that of those with early-onset CD (<40 years). CD patients were highly likely to develop CRC. Early-onset CD patients were significantly associated with an increased risk of CRC than matched individuals without CD. However, among CD patients, late-onset CD was significantly associated with an increased risk of CRC.

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Colorectal Cancer in North-Eastern Iran: a retrospective, comparative study of early-onset and late-onset cases based on data from the Iranian hereditary colorectal cancer registry

BMC Cancer ◽

10.1186/s12885-021-09132-5 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Benyamin Hoseini ◽

Zahra Rahmatinejad ◽

Ladan Goshayeshi ◽

Robert Bergquist ◽

Amin Golabpour ◽

...

Keyword(s):

Colorectal Cancer ◽

High Risk ◽

Early Onset ◽

Late Onset ◽

Statistical Significance ◽

City Hospital ◽

Genetic Characteristics ◽

Eastern Iran ◽

North Eastern ◽

Tumour Location

Abstract Background The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. Methods This retrospective study, carried out over a three-year follow-up period (2014–2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years. Results From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS. Conclusion The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.

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