The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of 50 controls, 112 patients with benign diseases and 534 patients with malignancies. Using 15 U/ml as the cutoff, no healthy subjects, patients with benign diseases (excluding liver cirrhosis) or patients with no evidence of disease (45 patients) had serum levels higher than this limit. Abnormal c-erbB-2 levels were found in 38.5% (10 of 26) of the patients with liver cirrhosis and in 26.7% (8 of 30) of those patients with primary liver cancer. No differences were found between the c-erbB-2 serum concentrations in liver cirrhosis or primary liver cancer, suggesting the possible catabolism of this antigen in the liver. Abnormal levels of this antigen were found in 20% (56 of 278) of the patients with breast carcinoma (lo-coregional 7%, metastases 41.5%), in 21 % (6 of 28) of ovarian carcinomas (stage I-II 0%, stage III-IV 42.8%), in 21% (3 of 14) of the colorectal tumors (locoregional 0%, metastases 30%), and in 13.3% (11 of 83) of the patients with lung cancer (locoregional 11.5%, metastases 16%). C-erbB-2 sensitivity in other patients with advanced disease was: 25% (9 of 36) in prostatic cancer; 22% (2 of 9) in gastric cancer, and 11% (1 of 9) in vesical tumors. When patients with liver metastases were excluded, abnormal c-erbB-2 serum levels were only found in breast, lung, prostatic and ovarian carcinomas. C-erbB-2 sensitivity in patients with lung cancer was related to tumor histology with significantly higher values in non-small cell lung cancer (mainly adenocarcinomas) than in patients with small cell lung cancer (p < 0.013). C-erbB-2 concentrations in patients with breast cancer were significantly higher in patients with recurrence (mainly bone and liver metastases) and in patients with progesterone receptor-negative ( < 15 fmol/mg) tumors (p < 0.01). In conclusion, c-erbB-2 is not a specific tumor marker and abnormal serum levels may be found in patients with liver pathologies. Its sensitivity suggests its possible application as a tumor marker in breast, ovarian, lung (mainly adenocarcinomas) and prostatic tumors.

10.1159/000218029

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Sa1897 Novel Evidence for Interleukin-8 (IL-8) As a Predictive Biomarker of Response to 5fluorouracil Based Chemotherapy in Colorectal Cancer

Gastroenterology (2014)

Lucía Pérez–Carbonell Cecilia Egoavil Estefanía Rojas Cristina Alenda María Rodríguez‐Soler

10.1016/s0016-5085(14)61166-5

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New Insights into a Controversial Topic: The Methylation–Cancer Connection

Gastroenterology (2007)

Isabel González-Garcı́a Antoni Castells

DNA demethylation

10.1053/j.gastro.2007.03.089

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Postoperative Surveillance in Patients With Colorectal Cancer Who Have Undergone Curative Resection: A Prospective, Multicenter, Randomized, Controlled Trial

Journal of Clinical Oncology (2005)

Francisco Rodríguez‐Moranta Joan Saló Àngels Arcusa Jaume Boadas Virgı́nia Piñol

Purpose Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability. Patients and Methods Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added. Results A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (hazard ratio [HR] = 0.87; 95% CI, 0.49 to 1.54; P = .62). However, the intensive strategy was associated with higher overall survival in patients with stage II tumors (HR = 0.34; 95% CI, 0.12 to 0.98; P = .045) and in those with rectal lesions (HR = 0.09; 95% CI, 0.01 to 0.81; P = .03), mainly due to higher rate of resectability for recurrent tumors. Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumor recurrence in the intensive arm. Conclusion A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors. Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up, at least.

Carcinoembryonic antigen

Multicenter trial

10.1200/jco.2005.02.0826

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Desequilibrios territoriales y políticas de cohesión en la Unión Europea.

Antoni Castells Marta Espasa Queralt

Source

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Cribado del cáncer colorrectal

Gastroenterología y Hepatología (2011)

Antoni Castells

10.1016/s0210-5705(11)70009-7

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Cribado del cáncer colorrectal: el trigo está en las gavillas y la casa tiene cimientos Colorectal cancer screening: actions have been taken and the cart has been put behind the horse

DOAJ (DOAJ: Directory of Open Access Journals) (2012)

Rafel Guayta-Escolies Antoni Castells Francesc Macià Gemma Binefa

Cart

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Genetic architectures of proximal and distal colorectal cancer are partly distinct

WOS (2021)

Jeroen R. Huyghe Tabitha A. Harrison Stephanie A. Bien Heather Hampel Jane C. Figueiredo

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Genetic architectures of proximal and distal colorectal cancer are partly distinct

medRxiv (Cold Spring Harbor Laboratory) (2020)

Jeroen R. Huyghe Tabitha A. Harrison Stephanie A. Bien Heather Hampel Jane C. Figueiredo

ABSTRACT Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for sporadic CRC differs by anatomical subsite of the primary tumor has not been examined. Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48,214 CRC cases and 64,159 controls of European ancestry. We characterized effect heterogeneity at CRC risk loci using multinomial modeling. Results We identified 13 loci that reached genome-wide significance (P <5×10 −8 ) and that were not reported by previous GWAS for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumor. Significance of this study What is already known about this subject? Heterogeneity among colorectal cancer (CRC) tumors originating at different locations of the colorectum has been revealed in somatic genomes, epigenomes, and transcriptomes, and in some established environmental risk factors for CRC. Genome-wide association studies (GWAS) have identified over 100 genetic variants for overall CRC risk; however, a comprehensive analysis of the extent to which genetic risk factors differ by the anatomical sublocation of the primary tumor is lacking. What are the new findings? In this large consortium-based study, we analyzed clinical and genome-wide genotype data of 112,373 CRC cases and controls of European ancestry to comprehensively examine whether CRC case subgroups defined by anatomical sublocation have distinct germline genetic etiologies. We discovered 13 new loci at genome-wide significance ( P <5×10 −8 ) that were specific to certain anatomical sublocations and that were not reported by previous GWAS for overall CRC risk; multiple lines of evidence support strong candidate target genes at several of these loci, including PTGER3, LCT, MLH1, CDX1, KLF14, PYGL, BCL11B , and BMP7 . Systematic heterogeneity analysis of genetic risk variants for CRC identified thus far, revealed that the genetic architectures of proximal and distal CRC are partly distinct. Taken together, our results further support the idea that tumors arising in different anatomical sublocations of the colorectum may have distinct etiologies. How might it impact on clinical practice in the foreseeable future? Our results provide an informative resource for understanding the differential role that genes and pathways may play in the mechanisms of proximal and distal CRC carcinogenesis. The new insights into the etiologies of proximal and distal CRC may inform the development of new precision prevention strategies, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Our findings suggest that future studies of etiological risk factors for CRC and molecular mechanisms of carcinogenesis should take into consideration the anatomical sublocation of the colorectal tumor.

Genome-wide Association Study

Genetic Association

Genetic architecture

10.1101/2020.05.01.20087957

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