A Summary of the Fight Colorectal Cancer Working Meeting: Exploring Risk Factors and Etiology of Sporadic Early-Age Onset Colorectal Cancer

Dwyer, Andrea; Murphy, Caitlin C.; Boland, C. Richard; Garcia, Reese; Hampel, Heather; Limburg, Paul J.; Lowery, Jan T.; Zauber, Ann G.; Waring, Stephen C.; Worrall, Sharyn; Perea, José; Siegel, Rebecca L.; Lee, Jeffrey; Molmenti, Christine L. Sardo; Sears, Cynthia L.; Buckhaults, Phillip; Hayes, Richard B.; Hussan, Hisham; Miranda, Noel F C C de; Palles, Claire; Díaz, Luis A.; Song, Mingyang; Cercek, Andrea; Lieu, Christopher H.; Patel, Swati; Karlitz, Jordan J.; Cao, Yin; Demb, Joshua; Blatchford, Patrick J.; Risendal, Betsy; Weltzien, Elsa; Wali, Anil; Daschner, Phil; Loomans-Kropp, Holli A.; Flores, Rhonda; Levell, Caleb; Wehling, Karen; Martin, Julia; Pesmen, Curt; Kuchar, Violet; Soisson, Ryan; Davis, Anjee; Ahnen, Dennis J.

doi:10.1053/j.gastro.2019.04.049

Cited by 34 publications

(21 citation statements)

References 24 publications

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“…Only 21% of patients presented with stage I or II disease, while 39% of patients had metastatic disease at diagnosis. Overall, our findings are in line with other studies that suggest that the incidence of rectal cancer is increasing most rapidly in young adults and that these patients tend to be diagnosed with advanced disease stage [19,20,21,22]. It is however worth noting that other epidemiological data from Europe suggests that the largest increase in CRC incidence in young adults is in fact of colon rather than rectal origin [3,23], thereby, challenging recent suggestions of screening strategies in young adults with flexible sigmoidoscopy alone [24].…”

Section: Discussionsupporting

confidence: 92%

“…In the USA, there is data to suggest that there are persistent disparities by race/ethnicity and possibly socio-economic status. However, these disparities may reflect the relative distribution of other risk factors that are known to be associated with CRC, such as obesity and type II diabetes in these subgroups [17,18,19]. Our cohort had a median BMI that was within the normal distribution, median of 24.9 kg/m 2 , albeit at the uppermost limit of normality.…”

Section: Discussionmentioning

confidence: 95%

“…This may have been due to the fact that other retrospective studies in EOCRC included a younger group by only including patients aged <40 years old. It is well established that the younger the median age of the EOCRC cohort, the higher the rate of hereditary etiology [12,19]. Patients with known hereditary syndromes remain an important proportion of the EOCRC population that require specialist cancer genetics input and specialized surveillance strategies.…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center

Georgiou

Khakoo

Edwards

et al. 2019

Cancers

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The incidence of early onset colorectal cancer (EOCRC) is rapidly increasing, but there remains paucity of outcome data for young CRC patients. We reviewed the characteristics and outcomes of 241 adults, age <50, who were diagnosed with EOCRC between January 2009 and December 2014. Median age was 42, 56% were male, and 7% had hereditary etiology. Seventy percent had left-sided primaries. At diagnosis, 11%, 50%, and 39% had stage II, III, and IV CRC. Of the patients with stage II and III CRC who underwent curative surgery, 60% and 88% had adjuvant chemotherapy, with 5-year relapse free survival of 82% and 74% respectively. Of the 123 patients with metastatic (m) EOCRC, 93%, 63%, 33%, and 12% had 1st, 2nd, 3rd, and 4th line systemic anticancer therapy (SACT) respectively. For first line SACT, 99% had doublet chemotherapy, with bevacizumab or an anti-EGFR antibody in 57%. Median overall survival (mOS) of mEOCRC patients was 20.1 months (95% C.I: 15.9–23.2). Younger age and signet cells were associated with shorter mOS, whereas more lines of SACT and curative metastasectomy with longer mOS. Metastatic EOCRC patients had poorer outcomes than expected, despite optimal multimodality treatment. This suggests an aggressive disease biology that warrants further research and therapy development.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center

Georgiou

Khakoo

Edwards

et al. 2019

Cancers

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“…Generally, postoperative pathological analysis results are used to evaluate the degree of malignancy in terms of TNM-stage-based invasion depth, lymph node metastasis, pathological type and tumor growth pattern, so as to predict the prognosis and formulate auxiliary treatment programs [2,3] . With the deepening of biomarker research, various types of indicators had been found to be related to the biological characteristics even prognosis survival of colorectal cancer, including genetic molecules, blood parameters and even nutritional indexes [4][5][6] . Therefore, the…”

Section: Introductionmentioning

confidence: 99%

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood

Li¹,

Wu²,

Xing³

et al. 2020

J. Cancer

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Background: Many indicators of peripheral blood in routine blood test (BRT) results of colorectal cancer (CRC) patients are related to prognosis. Currently, indexes such as NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio) and LMR (Lymphocyte-to-Monocyte ratio) evaluate the survival risk of patients by assessing the inflammatory-immune status of CRCs. These indexes are more comprehensive and accurate than independent estimates. We hope to design more effective indexes through fully considering the correlation and significance between BRT indicators and prognosis, so as to play a guiding role in clinical malignant estimation of CRCs. Methods: 701 CRCs in training set and 256 CRCs in test set were included in the study samples, and their clinical data, tumor pathology results and peripheral blood routine results were collected. The prognosis, progression, and survival status of all patients were determined after follow-up. Above data were used for statistical analysis and designing new indexes. Results: It was found that high NE, MONO, RDW-CV/SD and PLT in peripheral blood indicated poor prognosis of DFS and OS. Conversely, CRCs with postoperative tumor progression or death had lower LY, EO, RBC, HGB, HCT, MCV, MCH, MCHC, PDW, and P-LCR. IRR, ARR and CRR related to infection, anemia and coagulation were designed respectively using the largest AUC indicators (P<0.05) selected by ROC curve. The formula: IRR= (NE*MONO)/(LY*EO); ARR= (HGB*MCHC)/RDW-CV; CRR=PLT/PDW. Results of Kaplan-Meier survival analysis and multivariate COX proportional hazard analysis adjusted for age, gender, TNM stage, infiltration, adhesion showed IRR, ARR, CRR were all able to be used as the evaluation standard of survival of CRC. The result was also authenticated in the test set. Conclusion: We designed three different prognostic indexes of colorectal cancer, IRR, ARR and CRR, which could be used as risk indicators of CRC prognosis, tumor progression and survival.

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“…Finally, it has been shown that EO-CRC incidence has raised across successive birth cohorts, suggesting the implication of exposures increasingly prevalent during childhood. Potential culprits are represented by cesarean delivery, absence of breastfeeding, prenatal/perinatal/infancy antibiotic use (which impacts the health of the gut microbiota) and changes in childhood diet [71]. Sedentary lifestyle during childhood, and specifically TV viewing time, has been also correlated with an increasing risk of EO-CRC [29] (Figure 1).…”

Section: Increased Crc Incidence In the Young Adult Population: Molecmentioning

confidence: 99%

Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

2019

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Colorectal cancer (CRC) is the third commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Global CRC burden is expected to increase by 60% in the next decade, with low-income countries experiencing an escalation of CRC incidence and mortality in parallel to the adoption of western lifestyles. CRC incidence is also sharply increasing in individuals younger than 50 years, often presenting at advanced stages and with aggressive features. Both genetic and environmental factors have been recognized as major contributors for the development of CRC, the latter including diet-related conditions such as chronic inflammation and obesity. In particular, a diet rich in fat and sugars (Western-style diet, WSD) has been shown to induce multiple pathophysiological changes in the intestine linked to an increased risk of CRC. In this scenario, dietary factors have been recently shown to play novel unexpected roles in the regulation of intestinal stem cells (ISCs) and of the gut microbiota, which represent the two main biological systems responsible for intestinal homeostasis. Furthermore, diet is increasingly recognized to play a key role in the neoplastic transformation of ISCs and in the metabolic regulation of colorectal cancer stem cells. This review illustrates novel discoveries on the role of dietary components in regulating intestinal homeostasis and colorectal tumorigenesis. Particular focus is dedicated to new areas of research with potential clinical relevance including the effect of food components on ISCs and cancer stem cells (CSCs), the existence of CRC-specific microbial signatures and the alterations of intestinal homeostasis potentially involved in early-onset CRC. New insights on the role of dietary factors in intestinal regulation will provide new tools not only for the prevention and early diagnosis of CRC but also for improving the effectiveness of current CRC therapies.

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A Summary of the Fight Colorectal Cancer Working Meeting: Exploring Risk Factors and Etiology of Sporadic Early-Age Onset Colorectal Cancer

Cited by 34 publications

References 24 publications

Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center

Outcomes of Patients with Early Onset Colorectal Cancer Treated in a UK Specialist Cancer Center

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood

Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

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