Colorectal adenocarcinoma in patients under 45 years of age

Mitry, Emmanuel; Benhamiche, Anne-Marie; Jouve, Jean-Louis; Clinard, François; Finn-Faivre, Corinne; Faivre, Jean

doi:10.1007/bf02234737

Cited by 89 publications

(24 citation statements)

References 15 publications

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“…Of course, younger patients are likely to undergo more aggressive therapy including chemotherapy or repeated surgical resection for metastatic disease that may improve the poorer prognosis given for EOCRC. Although partly contradictory with older studies, some of which were global analyses based on registries, the present work provides reliable results for the same aforementioned reasons [32]–[35]. Overall, sporadic EOCRC presents as an aggressive disease with distal location, high tumor stage and no clear histological specificity.…”

Section: Discussioncontrasting

confidence: 82%

Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

et al. 2014

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Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected. Patients aged 45–60 years were excluded to help define “young” and “old” groups. Thirty-nine cases of sporadic EOCRC (patients≤45 years with microsatellite stable tumors) were compared to both microsatellite stable tumors from older patients (36 cases, patients>60 years) and to groups of patients with microsatellite instability. Each group was tested for TP53, KRAS, BRAF, PIK3CA mutations and the presence of a methylator phenotype. Gene expression profiles were also used for pathway analysis. Compared to microsatellite stable CRC from old patients, sporadic EOCRC were characterized by distal location, frequent synchronous metastases and infrequent synchronous adenomas but did not have specific morphological characteristics. A familial history of CRC was more common in sporadic EOCRC patients despite a lack of identified hereditary conditions (p = 0.013). Genetic studies also showed the absence of BRAF mutations (p = 0.022) and the methylator phenotype (p = 0.005) in sporadic EOCRC compared to older patients. Gene expression analysis implicated key pathways such as Wnt/beta catenin, MAP Kinase, growth factor signaling (EGFR, HGF, PDGF) and the TNFR1 pathway in sporadic EOCRC. Wnt/beta catenin signaling activation was confirmed by aberrant nuclear beta catenin immunostaining (p = 0.01). This study strongly suggests that sporadic EOCRC is a distinct clinico-molecular entity presenting as a distal and aggressive disease associated with chromosome instability. Furthermore, several signaling pathways including the TNFR1 pathway have been identified as potential biomarkers for both the diagnosis and treatment of this disease.

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Section: Discussioncontrasting

confidence: 82%

Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

et al. 2014

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“…The exact cause of this difference is not known; however, it can be postulated that the higher proportion of younger patients in the underdeveloped countries can be a reason for this skewed finding [16]. However, more interesting is the hypothesis that sporadic early onset colorectal cancer is a biologically and clinically distinct entity, accounting for its aggressive presentation and poorer survival [16, 17, 20]. …”

Section: Discussionmentioning

confidence: 99%

“…It has been hypothesized that early onset colorectal cancer is a biologically and clinically distinct disease where younger individuals have more aggressive disease and worse survival [16, 17]. A recent population based study from Pakistan also showed that younger patients presented with disease which was more likely to be poorly differentiated and at a more advanced stage at diagnosis [13].…”

Section: Introductionmentioning

confidence: 99%

Clinical Features and Outcome of Sporadic Colorectal Carcinoma in Young Patients: A Cross-Sectional Analysis from a Developing Country

et al. 2014

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Background. Early onset colorectal carcinoma (CRC) is rare and has been hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and worse survival. Methods. Data for 131 patients was collected by retrospective chart review. Cox proportional hazard model was used to compute prevalence ratios and 95% confidence intervals. Results. Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. The mean age was 33.3 ± 7.9 years and the male to female ratio was 2 : 1. Colon and rectal cancers accounted for 55% and 45% of patients, respectively. 96% of rectal carcinoma patients received appropriate therapy as opposed to 65% of colon cancers. On multivariable analysis, appropriate reception of therapy (PR 4.99; 95% CI, 1.21–20.6) and signet ring morphology (PR 2.40; 95% CI, 1.33–4.32) were significantly associated with rectal cancers as opposed to colon cancer. Kaplan-Meier analysis revealed a trend towards inferior survival for rectal carcinoma 2 years after diagnosis. Conclusion.A high prevalence of early onset CRC was noted in the study. A trend towards inferior survival was seen in patients with rectal cancer. This finding raises the possibility of rectal carcinoma being an aggressive subset of young CRC.

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“…These inconsistent could be explained by: First, the current definition of young CRC patients remains controversial. Although majority of studies in the literature used the cutoff age of 40 years to denote a young patients with CC [3], [4], [5], [6], [7], some other studies used the cutoff age of 30 years [4], [15], 25 years [16] or others [17], [18], [19]. Second, young age consisted wide age range of population, which maybe an inherent characteristic of heterogeneous, different composition of young subgroup may cause different results.…”

Section: Discussionmentioning

confidence: 99%

Pathological Features and Survival Outcomes of Young Patients with Operable Colon Cancer: Are They Homogeneous?

Zhuo

Cai

et al. 2014

PLoS ONE

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ObjectiveTo compare the pathological features and survival outcomes at different age subgroups of young patients with colon cancer.MethodsUsing Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 2,861 young patients with colon cancer diagnosed between 1988 and 2005 treated with surgery. Patients were divided into four groups: group 1 (below 25 years), group 2 (26–30 years), group 3 (31–35 years) and group 4 (36–40 years). Five-year cancer specific survival data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.ResultsThere were significant different among four groups in pathological grading, histological type, AJCC stage, current standard (≥12 lymph nodes retrieval), mean number of lymph nodes examined and positive lymph nodes (p<0.001). The 5-year cause specific survival was 71.0% in group 1, 75.1% in group 2, 80.6% in group 3 and 82.5% in group 4, which had significant difference in both univariate (P = 0.002) and multivariate analysis (P = 0.041).ConclusionsYoung patients with colon cancer at age 18–40 years are essentially a heterogeneous group. Patients at age 31–35, 36–40 subgroups have more favorable clinicopathologic characteristics and better cancer specific survival than below 30 years.

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Colorectal adenocarcinoma in patients under 45 years of age

Cited by 89 publications

References 15 publications

Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

Sporadic Early-Onset Colorectal Cancer Is a Specific Sub-Type of Cancer: A Morphological, Molecular and Genetics Study

Clinical Features and Outcome of Sporadic Colorectal Carcinoma in Young Patients: A Cross-Sectional Analysis from a Developing Country

Pathological Features and Survival Outcomes of Young Patients with Operable Colon Cancer: Are They Homogeneous?

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