Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy.
Tumour Biol
; 44(1): 1-16, 2022.
Article
en En
| MEDLINE
| ID: mdl-35180141
ABSTRACT
BACKGROUND:
It was previously shown in three subpopulations that subjects not identified with colorectal cancer (CRC) at bowel endoscopy, but with increased serological cancer-associated protein biomarker levels had an increased risk of being diagnosed with subsequent malignant diseases.OBJECTIVE:
The aim of the present study was to perform a pooled analysis of subjects from the three subpopulations and subsequently validate the results in an independent study. The study population denoted the training set includes Nâ=â4,076 subjects with symptoms attributable to CRC and the independent validation set Nâ=â3,774 similar subjects.METHODS:
Levels of CEA, CA19-9, TIMP-1 and YKL-40 were determined in blood samples collected prior to diagnostic bowel endoscopy. Follow-up of subjects not diagnosed with CRC at endoscopy, was ten years and identified subjects diagnosed with primary intra- or extra-colonic malignant diseases. The primary analysis was time to a newly diagnosed malignant disease and was analyzed with death as a competing risk in the training set. Subjects with HNPCC or FAP were excluded. The cumulated incidence was estimated for each biomarker and in a multivariate model. The resulting model was then validated on the second study population.RESULTS:
In the training set primary malignancies were identified in 515 (12.6%) of the 4,076 subjects, who had a colorectal endoscopy with non-malignant findings. In detail, 33 subjects were subsequently diagnosed with CRC and 482 subjects with various extra-colonic cancers. Multivariate additive analysis of the dichotomized biomarkers demonstrated that CEA (HRâ=â1.50, 95% CI1.21-1.86, pâ<â0.001), CA19-9 (HRâ=â1.41, 95% CI1.10-1.81, pâ=â0.007) and TIMP-1 (HRâ=â1.25 95% CI 1.01-1.54, pâ=â0.041) were significant predictors of subsequent malignancy. The cumulated incidence at 5 years landmark time was 17% for those subjects with elevated CEA, CA19-9 and TIMP-1 versus 6.7% for those with low levels of all. When the model was applied to the validation set the cumulated 5-year incidence was 10.5% for subjects with elevated CEA, CA19-9 and TIMP-1 and 5.6% for subjects with low levels of all biomarkers. Further analysis demonstrated a significant interaction between TIMP-1 and age in the training set. The age dependency of TIMP-1 indicated a greater risk of malignancy in younger subjects if the biomarker was elevated. This observation was validated in the second set.CONCLUSION:
Elevated cancer-associated protein biomarker levels in subjects with non-malignant findings at large bowel endoscopy identifies subjects at increased risk of being diagnosed with subsequent primary malignancy. CEA, CA19-9 and TIMP-1 were significant predictors of malignant disease in this analysis. TIMP-1 was found dependent on age. The results were validated in an independent symptomatic population.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos de Carbohidratos Asociados a Tumores
/
Antígeno Carcinoembrionario
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Inhibidor Tisular de Metaloproteinasa-1
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Neoplasias
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Tumour Biol
Asunto de la revista:
NEOPLASIAS
Año:
2022
Tipo del documento:
Article
País de afiliación:
Dinamarca