High frequency of KRAS mutation in early onset colorectal adenocarcinoma: implications for pathogenesis

Watson, Rao; Liu, Ta‐Chiang; Ruzinova, Marianna B.

doi:10.1016/j.humpath.2016.06.010

Cited by 39 publications

(38 citation statements)

References 32 publications

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“…Only papillary and colonic types showed KRAS mutations. This finding is in agreement with results in colorectal and lung cancers, in which KRAS was found to be frequent in early‐stage tumors . TP53 mutations were seen in all subtypes but least frequently in mucinous type (25% vs 33%‐60%).…”

Section: Discussionsupporting

confidence: 92%

Genomic profiling of intestinal‐type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes

et al. 2017

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Section: Discussionsupporting

confidence: 92%

Genomic profiling of intestinal‐type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes

et al. 2017

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“…Only a very small number of early‐onset patients with metastatic disease (28 of 634 or 4%) had a recognized hereditary syndrome or IBD in the MDACC molecular cohort. Prior reports have suggested that a minority of early‐onset CRC cases are attributable to hereditary syndromes or a sporadic DNA MMR deficiency, a feature supported by our study . The screening of high‐risk patients with predisposing hereditary syndromes increases the likelihood of diagnosing cancer at earlier stages.…”

Section: Discussionsupporting

confidence: 84%

“…The incidence and mortality for individuals 50 years old or older have decreased because of preventive screening; however, the incidence has increased 1% to 3% annually for individuals younger than 50 years during the same time . Although an estimated 4% to 21% of early‐onset CRCs are related to hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis, or other genetic syndromes, the majority are sporadic . Because of the discrepant trends in incidence between early‐onset CRC (age < 50 years) and late‐onset CRC (age ≥ 50 years) and the large number of early‐onset patients without identifiable predisposing genetic conditions, further characterization of early‐onset CRC is required.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and molecular characterization of early‐onset colorectal cancer

Willauer

Liu

Pereira

et al. 2019

Cancer

239

230

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Background Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early‐onset CRC that differentiate these patients from patients 50 years old or older. Methods Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence. Results This retrospective review of more than 36,000 patients with CRC showed that early‐onset patients were more likely to have microsatellite instability (P = .038), synchronous metastatic disease (P = .009), primary tumors in the distal colon or rectum (P < .0001), and fewer BRAF V600 mutations (P < .001) in comparison with patients 50 years old or older. Patients aged 18 to 29 years had fewer adenomatous polyposis coli (APC) mutations (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35‐0.90; P = .015) and an increased prevalence of signet ring histology (OR, 4.89; 95% CI, 3.23‐7.39; P < .0001) in comparison with other patients younger than 50 years. In patients younger than 40 years, CMS1 was the most common subtype, whereas CMS3 and CMS4 were uncommon (P = .003). CMS2 was relatively stable across age groups. Early‐onset patients with inflammatory bowel disease were more likely to have mucinous or signet ring histology (OR, 5.54; 95% CI, 2.24‐13.74; P = .0004) and less likely to have APC mutations (OR, 0.24; 95% CI, 0.07‐0.75; P = .019) in comparison with early‐onset patients without predisposing conditions. Conclusions Early‐onset CRC is not only distinct from traditional CRC: special consideration should be given to and further investigations should be performed for both very young patients with CRC (18‐29 years) and those with predisposing conditions. The etiology of the high rate of CMS1 in patients younger than 40 years deserves further exploration.

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“…Other work has shown low levels of microsatellite instability in colorectal cancer in young adults. Additionally, there is a prevalence of mutations in genes such as β‐catenin and KRAS . Interestingly, the combination of altered environmental exposures and different tumour biology suggests that young‐adult colorectal cancer may be a different disease from later‐onset disease.…”

Section: Discussionmentioning

confidence: 99%

Demographic trends in the incidence of young-onset colorectal cancer: a population-based study

Chambers

Dixon

White

et al. 2020

British Journal of Surgery

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Background Evidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking. Methods A population‐based cohort study was carried out including all adults aged 20–49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD‐9/10 codes for colorectal cancer. Temporal trends in age‐specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression. Results A total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20–29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England. Conclusion Colorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.

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High frequency of KRAS mutation in early onset colorectal adenocarcinoma: implications for pathogenesis

Cited by 39 publications

References 32 publications

Genomic profiling of intestinal‐type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes

Genomic profiling of intestinal‐type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes

Clinical and molecular characterization of early‐onset colorectal cancer

Demographic trends in the incidence of young-onset colorectal cancer: a population-based study

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