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Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer.

ABSTRACT: PURPOSE:The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer. EXPERIMENTAL DESIGN:DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established. RESULTS:Overall genomic alteration rates in the younger (<40) and older (?50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, TP53 (FDR < 0.01) and CTNNB1 (FDR = 0.01) alterations were more common in younger patients with colorectal cancer, and APC (FDR < 0.01), KRAS (FDR < 0.01), BRAF (FDR < 0.01), and FAM123B (FDR < 0.01) were more commonly altered in older patients with colorectal cancer. In the MSI-H cohort, the majority of genes showed similar rate of alterations in all age groups, but with significant differences seen in APC (FDR < 0.01), BRAF (FDR < 0.01), and KRAS (FDR < 0.01). CONCLUSIONS:Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biology and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer.

SUBMITTER: Lieu CH

PROVIDER: S-EPMC6774873 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer.

Lieu Christopher H CH Golemis Erica A EA Serebriiskii Ilya G IG Newberg Justin J Hemmerich Amanda A Connelly Caitlin C Messersmith Wells A WA Eng Cathy C Eckhardt S Gail SG Frampton Garrett G Cooke Matthew M Meyer Joshua E JE

Clinical cancer research : an official journal of the American Association for Cancer Research 20190626 19

<h4>Purpose</h4>The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer.<h4>Experimental design</h4>DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, ...[more]

PMID: 31243121

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Project description:Background and aimsThe annual incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear.MethodsWe searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early- and later-onset patients and performed a prognostic analysis. Random-effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer-special survival (CSS), and disease-free survival (DFS). Network meta-analysis (NMA) was used to compare patients' long-term prognoses in different age subgroups.ResultsAfter 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta-analysis of the 5-year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74-0.99; relative risk [RR] 0.83, 95% CI, 0.78-0.89). No difference in prognosis was found between the two groups in terms of 5-year CSS (RR 0.99, 95% CI, 0.93-1.05), 5-year DFS (RR 0.90, 95% CI, 0.74-1.09), and short-term OS. In the NMA, patients aged <30 years had the worst outcome (surface under the cumulative ranking curve [SUCRA], 15.8%) in 5-year OS; consistent results were observed in the analysis of 5-year CSS (<30 years, SUCRA 4.5%), but the difference was not statistically significant.ConclusionAlthough patients with early-onset CRC had better OS than those with later-onset CRC, there was no difference in the CSS. Meanwhile, the trend for survival was worse in younger patients, especially in those ages 18-29 years. Thus, more attention should be paid to early diagnosis and treatment of EOCRC.Systematic review and meta‐analysis registrationThe systematic review and Meta-analysis protocol was registered with PROSPERO (registration number CRD42022334697).

Dataset Information

Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer.

Publications

Comprehensive Genomic Landscapes in Early and Later Onset Colorectal Cancer.

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