Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

Lorentzen, Jon A.; Grzyb, Krzysztof; Angelis, Paula M. De; Hoff, Geir; Eide, Tor J.

doi:10.4137/cpath.s40143

Cited by 14 publications

(15 citation statements)

References 53 publications

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“…In our study, we linked precursor CRC lesions to a molecular pathway with the aim of determining whether this molecular signature could predict the development of advanced lesions at follow-up. As expected and according with previous studies, BRAF mutations were rarely found in conventional adenomas [ 21 – 24 ]. However, we found BRAF mutations in less than 40% of serrated lesions, which was clearly less frequent than previously reported for this type of polyps [ 25 – 26 ].…”

Section: Discussionsupporting

confidence: 92%

KRAS and BRAF somatic mutations in colonic polyps and the risk of metachronous neoplasia

et al. 2017

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Background & aimsHigh-risk features of colonic polyps are based on size, number, and pathologic characteristics. Surveillance colonoscopy is often recommended according to these findings. This study aimed to determine whether the molecular characteristics of polyps might provide information about the risk of metachronous advanced neoplasia.MethodologyWe retrospectively included 308 patients with colonic polyps. A total of 995 polyps were collected and tested for somatic BRAF and KRAS mutations. Patients were classified into 3 subgroups, based on the polyp mutational profile at baseline, as follows: non-mutated polyps (Wild-type), at least one BRAF-mutated polyp, or at least one KRAS-mutated polyp. At surveillance, advanced adenomas were defined as adenomas ≥ 10 mm and/or with high grade dysplasia or a villous component. In contrast, advanced serrated polyps were defined as serrated polyps ≥ 10 mm in any location, located proximal to the splenic flexure with any size or with dysplasia.ResultsAt baseline, 289 patients could be classified as wild-type (62.3%), BRAF mutated (14.9%), or KRAS mutated (22.8%). In the univariate analysis, KRAS mutations were associated with the development of metachronous advanced polyps (OR: 2.36, 95% CI: 1.22–4.58; P = 0.011), and specifically, advanced adenomas (OR: 2.42, 95% CI: 1.13–5.21; P = 0.023). The multivariate analysis, adjusted for age and sex, also showed associations with the development of metachronous advanced polyps (OR: 2.27, 95% CI: 1.15–4.46) and advanced adenomas (OR: 2.23, 95% CI: 1.02–4.85).ConclusionsOur results suggested that somatic KRAS mutations in polyps represent a potential molecular marker for the risk of developing advanced neoplasia.

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Section: Discussionsupporting

confidence: 92%

KRAS and BRAF somatic mutations in colonic polyps and the risk of metachronous neoplasia

et al. 2017

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“…The KRAS mutations (approximately, 90%) was found with a high detection rate within exon 2 (codons 12 and 13) and exon 3 (codon 61). According to clinical studies among all most common codons 12 and 13 mutations, only (p.G12D), (p.G12V), and (p.G13D) missense mutations, were more frequently specified to individuals with resected advanced neoplasia and CRC . Taking into consideration the experimental data, only low frequency distribution of p.G12D was detected as most abundant mutation in all patients with colorectal sporadic adenomas, in contradiction to other reports, which have obviously stated a higher percentage of somatic KRAS mutations in codons 12 and 13.…”

Section: Discussioncontrasting

confidence: 60%

“…According to clinical studies among all most common codons 12 and 13 mutations, only (p.G12D), (p.G12V), and (p.G13D) missense mutations, were more frequently specified to individuals with resected advanced neoplasia and CRC. 17,18 Taking into consideration the experimental data, only low frequency distribution of p.G12D was detected as most abundant mutation in all patients with colorectal sporadic adenomas, 16 in contradiction to other reports, which have obviously stated a higher percentage of somatic KRAS mutations in codons 12 and 13. Nonetheless, our data in CRC patients (p.G12D; 36%) was approximately in accordance with the previously published report.…”

Section: Discussionmentioning

confidence: 69%

KRAS mutation and abnormal expression of Cripto‐1 as two potential candidate biomarkers for detection of colorectal cancer development

Igder

Mohammadi-Asl

Azadpour³

et al. 2019

J of Cellular Biochemistry

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Colorectal cancer (CRC), regardless of standard procedures of treatment and screening, is still considered one of the deadliest cancers in the Western world, and in economically developed Asian countries, especially Iran. The current study was undertaken to investigate whether changes in the level of Cripto‐1 (CR‐1) expression and KRAS mutations have a cumulative effect on the onset and progression of CRC. Fifty colorectal tissue samples, including 35 colorectal carcinomas with matching adjacent mucosa, and 15 colorectal adenomas, were chosen for analysis. Twenty‐five CRC biopsies and 15 adenoma were analyzed for KRAS mutations by DNA sequencing (Sanger sequencing), and all 50 patients (35 CRCs and 15 adenomas) were evaluated by immunohistochemistry for the CR‐1 protein expression. The inducible somatic KRAS mutation (G12D) was observed in nine (36%) of CRC patients, and in two (13.3%) of adenoma patients. The CR‐1 expression level in both adenomas (P < .05) and carcinomas (P < .001), were significantly different, compared with the matching adjacent mucosa. The intensity of CR‐1 staining in adenomas was less than the intensity of staining, detected in the CRCs (P < .001). The G12D KRAS mutation and CR‐1 abnormalities are significantly associated as two signature biomarkers with potential clinical characteristics for the detection of CRC development.

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“…These occur in the proximal colon and are more likely to be missed during colonoscopies and lead to more aggressive forms of cancer [ 14 ]. Females were also found to have higher frequency of KRAS mutations in codon 12 than males, which again are associated with more advanced adenomas [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK

et al. 2018

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BackgroundColorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC.MethodsA cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality.ResultsOverall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes.ConclusionsAs there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.

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Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

Cited by 14 publications

References 53 publications

KRAS and BRAF somatic mutations in colonic polyps and the risk of metachronous neoplasia

KRAS and BRAF somatic mutations in colonic polyps and the risk of metachronous neoplasia

KRAS mutation and abnormal expression of Cripto‐1 as two potential candidate biomarkers for detection of colorectal cancer development

A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK

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