Colorectal Cancer in the Young: Epidemiology, Prevention, Management

Siegel, Rebecca L.; Jakubowski, Christopher; Fedewa, Stacey A.; Davis, Anjee; Azad, Nilofer S.

doi:10.1200/edbk_279901

Cited by 166 publications

(157 citation statements)

References 129 publications

(148 reference statements)

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“…Regarding genomic mutations, several studies have reported that early-onset SRCC is associated with a de novo deletion of CDH1, which encodes a protein functioning as an adherens junction; this to some extent explains why early-onset SRCC is more likely to be metastatic [15,20]. Regarding clinical characteristics, the distinct sex distribution between early-onset SRCC and late-onset SRCC may also account for the high malignancy [21]. In addition to distant metastasis, we found that lymphatic vessel invasion was more frequent in early-onset patients, which suggests that early-onset SRCC has greater malignancy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Zhou¹,

Ge²,

Liu³

2020

BMC Gastroenterol

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Background There is little knowledge to date about the distant metastasis of early-onset gastric signet ring cell carcinoma (SRCC) or the difference in metastasis based on age. Therefore, we conducted a comprehensive retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database and data from our hospital. Methods Patients were collected from the SEER database and our hospital. Univariate and multivariate logistic regression analyses and propensity score matching (PSM) were used to identify risk factors for metastasis. K-M survival curves were generated to analyse patient survival. Results In total, we retrieved 2052 EOGC patients diagnosed with SRCC from the SEER database and included 403 patients from our hospital. K-M survival curves showed that late-onset SRCC patients had worse survival than early-onset patients but that late-onset SRCC patients were less likely to have distant metastasis, as validated by SEER data (OR = 0.462, 95%CI, 0.272–0.787; P = 0.004) and our data (OR = 0.301, 95%CI, 0.135–0.672; P = 0.003). Multivariate logistic regression and PSM analysis revealed that age of 45 or younger was an independent risk factor for distant metastasis. Conclusion Our study showed that distant metastasis was more common in early-onset SRCC than in late-onset SRCC. However, further studies are needed to explore the potential aetiologic basis for this disparity.

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Section: Discussionmentioning

confidence: 99%

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Zhou¹,

Ge²,

Liu³

2020

BMC Gastroenterol

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“…Early-onset non-polyposis CRC is a distinct entity with unique genetic features. Accumulating data suggest that early-onset CRC may have distinct clinicopathological features, including a more frequent occurrence in the rectum (32-57.7%), manifesting as mucinous (12.6%) or signet ring (10.8%) carcinoma and exhibiting poor differentiation features (20.4%) on histological analysis, and that diagnosis is mostly made at stages III and IV ( 8 , 21 – 23 ). All of these features were also determined in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence suggests that early-onset CRC has a more progressive biological behavior and a worse prognosis ( 6 , 35 ). This subset of patients has comparatively more concerns in a number of aspects, including the effects of treatment on fertility ( 8 ). These features raise a compelling concern as to the identification of prognostic markers and optimal treatment strategies, which may differ from the older-aged subset of patients.…”

Section: Discussionmentioning

confidence: 99%

“…The incidence of CRC among adolescents and young adults has exhibited an increase over the past decades ( 1 – 3 ), particularly in patients aged 20–39 years ( 4 , 5 ). Early-onset CRC usually presents at an advanced stage at the time of diagnosis with a more aggressive biological behavior, which is unique to this subset of CRC ( 6 – 8 ). A study indicated that the prevalence of hereditary cancer syndromes in CRC patients aged 35 years or younger was ~35% ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

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Early‑onset colorectal cancer: A distinct entity with unique genetic features

Jiang

Shu²,

Lei

et al. 2020

Oncol Lett

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The aim of the present study was to elucidate the genetic features of early-onset colorectal cancer (CRC), particularly the genetic mutations that may be regarded as prognostic and/or predictive markers in CRC and other malignancies. In total, 40 patients with non-polyposis CRC aged 35 or younger were selected. The formalin-fixed, paraffin-embedded tumors acquired were subjected to mismatch repair (MMR) protein immunochemical staining and gene analysis with next-generation sequencing (44 exons, 17 genes; Ion Torrent Sequencing Platform). A total of 11 (27.5%) tumors presented with MMR protein deficiency (dMMR) and 26 (65%) tumors harbored one or more genetic mutations, including K-RAS proto-oncogene (35%), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA; 20%), B-Raf proto-oncogene (5%), erb-b2 receptor tyrosine kinase 2 (5%), discoidin domain receptor tyrosine kinase 2 (5%), N-RAS proto-oncogene (2.5%), KIT proto-oncogene (2.5%), TSC complex subunit 1 (2.5%), DNA methyltransferase 3 alpha (2.5%) and ABL proto-oncogene 1 (2.5%). Of the dMMR tumors, 81.8% (9/11) of cases presented with mutations in the tested genes, while only 58.6% (17/29) of the MMR-proficient (pMMR) tumors presented with these (P=0.158). PI3KCA was frequently mutated in dMMR tumors compared to pMMR tumors (P=0.025). In a subgroup with a family history of CRC, the dMMR status (P<0.001) and PIK3CA genetic mutation status (P=0.01) were more frequently observed compared to the other two groups (with a family history of other cancer types or no malignancy). Almost all patients who had relatives with CRC presented with both dMMR and other genetic mutations, while this was not observed in the patients who had relatives with other types of carcinoma. Certain genetic mutations that are rarely reported in CRC were only identified in those patients with a family history of carcinoma. In conclusion, non-polyposis CRC in young adults presents as a distinct entity with a unique set of genetic features. However, investigation of more cases in further studies is required to verify the present results.

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“…3,4 Tumor development, metastasis, and recurrence are the major contributors to CRC-related deaths; these processes are complex and largely unclear. 5,6 Unfortunately, approximately 25%-30% of patients are diagnosed at advanced stages mainly due to limited effective diagnostic techniques. 7 Accordingly, additional studies investigating CRC genesis and progression are of great significance for the identification of novel diagnostic and therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

<p>Long Noncoding RNA VPS9D1-AS1 Sequesters microRNA-525-5p to Promote the Oncogenicity of Colorectal Cancer Cells by Upregulating HMGA1</p>

Liu

Zhang

Jin

et al. 2020

CMAR

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Background: The long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) has emerged as a critical regulator in non-small-cell lung, gastric, and prostate cancers. In this study, we measured the expression levels of VPS9D1-AS1 in colorectal cancer (CRC) and determined the role of VPS9D1-AS1 in regulating the biological activities of CRC cells. In addition, we thoroughly elucidated the molecular mechanism mediating the oncogenic activities of VPS9D1-AS1 in CRC. Methods: The expression levels of VPS9D1-AS1 in CRC tissues and cell lines were detected via quantitative reverse transcription-polymerase chain reaction. Loss-of-function experiments were performed to detect the effects of VPS9D1-AS1 silencing on CRC cell proliferation, apoptosis, migration, and invasion as well as on tumor growth in vivo. Bioinformatics analysis predicted the potential microRNAs (miRNAs) interacting with VPS9D1-AS1, and this prediction was further confirmed via RNA immunoprecipitation and luciferase reporter assays. Results: Our results demonstrated the upregulated expression of VPS9D1-AS1 in CRC tissues and cell lines. Functionally, VPS9D1-AS1 interference suppressed CRC cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. In addition, the loss of VPS9D1-AS1 hindered tumor growth in vivo. Mechanistic studies identified VPS9D1-AS1 as a competing endogenous RNA in CRC cells, in which VPS9D1-AS1 acted as a molecular sponge of miR-525-5p and consequently increased the expression of high-mobility group AThook 1 (HMGA1). Moreover, rescue experiments revealed that the regulatory effects of VPS9D1-AS1 deficiency on CRC cells were abolished after miR-525-5p inhibition or HMGA1 restoration. Conclusion: The newly identified competing endogenous RNA pathway involving VPS9D1-AS1, miR-525-5p, and HMGA1 is implicated in the control of CRC progression and may provide an effective target for CRC diagnosis and therapy.

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Colorectal Cancer in the Young: Epidemiology, Prevention, Management

Cited by 166 publications

References 129 publications

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Comparison of metastasis between early-onset and late-onset gastric signet ring cell carcinoma

Early‑onset colorectal cancer: A distinct entity with unique genetic features

<p>Long Noncoding RNA VPS9D1-AS1 Sequesters microRNA-525-5p to Promote the Oncogenicity of Colorectal Cancer Cells by Upregulating HMGA1</p>

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