Publications by authors named "Paola Montenegro"

17 Publications

  • Page 1 of 1

Telemedicine and the current opportunities for the management of oncological patients in Peru in the context of COVID-19 pandemic.

Crit Rev Oncol Hematol 2021 Jan 22;157:103129. Epub 2020 Oct 22.

Dirección Médica, AUNA, Lima41, Peru.

COVID-19 pandemic is the more challenging public health emergency of the century, producing the collapse of health systems and unprecedented levels of morbidity and mortality around the world, especially in low resource settings. Patients with chronic diseases are the most affected, not only due to the high susceptibility to SARS-CoV-2 infection but also due to the decrease in opportunities for timely care. In this dark landscape, telemedicine, before limited to very specific scenarios, has become one of our main tools to manage cancer patients, particularly in Latin America where COVID-19 has had a strong impact on the public health. Telemedicine can provide rapid access to specialized cancer care in a scenario complicated, reducing the exposure of patients and healthcare personnel to the SARS-CoV-2. In this review, we would like to share our experience and our workflow using telemedicine at Oncosalud-AUNA, a private clinic in Peru.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581359PMC
January 2021

Detection of in gastric cancer tissue through histopathology, immunohistochemistry and real-time reverse transcription-PCR.

Future Microbiol 2020 Aug;15:1131-1137

Departamento de Patología, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru.

is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high density through H-E or IHC (p < 0.001). : H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.
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http://dx.doi.org/10.2217/fmb-2019-0280DOI Listing
August 2020

Helicobacter Pylori Detected in Tap Water of Peruvian Patients with Gastric Cancer.

Asian Pac J Cancer Prev 2019 Nov 1;20(11):3193-3196. Epub 2019 Nov 1.

Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.

Objective: To evaluate the correlation between the presence of H. pylori in paired samples of tap water and gastric cancer (GC) lesion in Lima city (Peru).

Material And Methods: Gastric tissue and tap-water samples were prospectively collected from 82 Gastric Cancer who lived in Lima. HspA and ureA genes were evaluated by qPCR in the samples.  Results: The median age of patients with GC was 63 years, 52.4% were men and stage-II in 36.6%. A home-living time> 10 years was reported in 84.1% of patients. Boiling water treatment was indicated in 85.4% of cases. H. pylori was detected in 69.5% of gastric tissues and in 12.2% of analyzed tap-water. There was no differences in gastric infection rates among those with or without water contamination (70% vs. 69.4%, p=0.971). Conclusion & Impact: H. pylori was found in tap-water samples, however, detection rates were lower than in gastric cancer samples. Other sources of infection transmission should be investigated.
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http://dx.doi.org/10.31557/APJCP.2019.20.11.3193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062988PMC
November 2019

Level of tumor-infiltrating lymphocytes and density of infiltrating immune cells in different malignancies.

Biomark Med 2019 12 17;13(17):1481-1491. Epub 2019 Oct 17.

Department of Pathology, Instituto Nacional de Enfermedades Neoplasicas, Lima 15038, Peru.

To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3, CD4, CD8, CD20, CD68 and CD163 cells by digital analysis. TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.
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http://dx.doi.org/10.2217/bmm-2019-0178DOI Listing
December 2019

Prevalence of Infection, Its Virulent Genotypes, and Epstein-Barr Virus in Peruvian Patients With Chronic Gastritis and Gastric Cancer.

J Glob Oncol 2019 09;5:1-9

Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.

Purpose: (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection.

Patients And Methods: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction.

Results: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The gene was detected in 79.9%; and alleles in 41.6% and 60.7%, respectively; and concurrent expression of and in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC ( < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate ( < .001) and multivariate ( = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status.

Conclusion: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.
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http://dx.doi.org/10.1200/JGO.19.00122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733198PMC
September 2019

Alpha-Synuclein Is a Target of Fic-Mediated Adenylylation/AMPylation: Possible Implications for Parkinson's Disease.

J Mol Biol 2019 05 27;431(12):2266-2282. Epub 2019 Apr 27.

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, 915 W State St., LILYG-227, West Lafayette, IN 47907, USA. Electronic address:

During disease, cells experience various stresses that manifest as an accumulation of misfolded proteins and eventually lead to cell death. To combat this stress, cells activate a pathway called unfolded protein response that functions to maintain endoplasmic reticulum (ER) homeostasis and determines cell fate. We recently reported a hitherto unknown mechanism of regulating ER stress via a novel post-translational modification called Fic-mediatedadenylylation/AMPylation. Specifically, we showed that the human Fic (filamentation induced by cAMP) protein, HYPE/FicD, catalyzes the addition of an adenosine monophosphate (AMP) to the ER chaperone, BiP, to alter the cell's unfolded protein response-mediated response to misfolded proteins. Here, we report that we have now identified a second target for HYPE-alpha-synuclein (αSyn), a presynaptic protein involved in Parkinson's disease. Aggregated αSyn has been shown to induce ER stress and elicit neurotoxicity in Parkinson's disease models. We show that HYPE adenylylates αSyn and reduces phenotypes associated with αSyn aggregation invitro, suggesting a possible mechanism by which cells cope with αSyn toxicity.
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http://dx.doi.org/10.1016/j.jmb.2019.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554060PMC
May 2019

Personalizing Precision Oncology Clinical Trials in Latin America: An Expert Panel on Challenges and Opportunities.

Oncologist 2019 08 25;24(8):e709-e719. Epub 2019 Mar 25.

AC Camargo Cancer Center, Sao Paulo, Brazil

The participation of patients in precision oncology trials needs to fulfill molecular-based selection criteria. This strongly limits accrual, and as a consequence, screening successes have decreased, costs have increased, and fewer subjects are enrolled. To achieve narrowed targets, studies have been forced to be multicenter and multinational to reach a larger pool of candidates. However, this globalization faces many challenges, as, for example, in the case of precision oncology trials. These trials have a complex structure that is dependent upon a high-tech infrastructure and knowledge in a dynamic environment. Given the movement of precision clinical cancer research to regions other than Europe and the U.S., it is important to evaluate the feasibility of performing such trials in lower-middle- and low-income countries. Here we critically discuss the advantages of conducting precision oncology clinical trials in Latin America and make suggestions on how to overcome the main challenges involved. IMPLICATIONS FOR PRACTICE: Precision clinical trials in oncology are studies that require candidates to have tumors with specific molecular alterations, which are considered the target for the trial experimental therapy. Because many molecular alterations are rare, fewer patients are enrolled. This has led to trials being forced to be multicenter and multinational, including trials in Latin America. This article discusses the challenges and opportunities to conduct precision oncology trials in Latin America, aiming to help sponsors and investigators to solve complex issues that ultimately lead to more of such trials being run in the region, potentially benefiting more Latin American patients with cancer.
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http://dx.doi.org/10.1634/theoncologist.2018-0318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693712PMC
August 2019

Tumor Protein p53 and K-ras Gene Mutations in Peruvian Patients with Gallbladder Cancer

Asian Pac J Cancer Prev 2019 Jan 25;20(1):289-294. Epub 2019 Jan 25.

Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. Email:

Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographic location on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factors have not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patients with gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a high gallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissue sections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection. Mutations in exons 5 to 8 of TP53 and codons 12, 13, and 61 of K-ras were examined using direct sequencing. Results: TP53 mutations were observed in 10 (33.3%) of patients, but K-ras mutations were absent. Nine (90%) TP53 mutations were point mutations (7 missense and 2 silent mutations), and the most frequent substitution was a G:C to A:T transition. G:C to A:T transitions at the CpG site or G:C to T:A transversions were found in one patient each. No significant differences were found in the frequency of TP53 and K-ras mutations among patients in the 5 countries. Conclusions: Our findings suggest that endogenous mechanisms and exogenous carcinogens may affect the carcinogenic process in Peruvian gallbladder cancer patients, similar to that in Bolivian patients. Further studies with a larger sample size are needed to clarify these findings.
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http://dx.doi.org/10.31557/APJCP.2019.20.1.289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485555PMC
January 2019

Oncological outcomes in extended time intervals betweenpreoperative chemoradiotherapy with capecitabine and surgery inoperable rectal adenocarcinoma.

Rev Gastroenterol Peru 2018 Jan-Mar;38(1):9-21

Department of Abdominal Surgery, Instituto Nacional de Enfermedades Neoplasicas. Lima, Peru.

Objective: To assess whether extended time intervals (8-12, 13-20 and >20 weeks) between the end of neoadjuvant chemoradiotherapy and surgery affect overall survival, disease-free survival.

Materials And Methods: Retrospective study in 120 patients with rectal adenocarcinoma without evidence of metastasis (T1-4/N0-2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant chemoradiotherapy with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at the National Cancer Institute of Peru. Dates were evaluated by Kaplan-Meier method, log- rank test and Cox regression analysis.

Results: Of the 120 patients, 70 were women (58%). The median age was 63(26-85) years. All received neoadjuvant chemoradiotherapy. No significant difference was found between the association of the median radial (0.6, 0.7 and 0.8 cm; p=0.826) and distal edge (3.0, 3.5 and 4.0 cm; p=0.606) with time interval groups and similarly the mean resected (18.8, 19.1 and 16.0; p=0.239) and infiltrated nodules (1.05, 1.29 and 0.41); p=0.585). The median follow-up time of overall survival and desease free survival was 40 and 37 months, respectively. No significant differences were observed in overall survival (79.0%, 74.6% and 71.1%; p=0.66) and disease-free survival (73.7%, 68.1% and 73.6%; p=0.922) according to the three groups studied at the 3-year of follow-up.

Conclusions: We found that widening the time intervals between the end of neoadjuvant chemoradiotherapy and surgery at 24 weeks does not affect the overall survival, disease-free survival and pathological outcomes. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery.
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November 2018

Draft Genome Sequence of the First New Delhi Metallo-β-Lactamase (NDM-1)-Producing Escherichia coli Strain Isolated in Peru.

Genome Announc 2018 Mar 29;6(13). Epub 2018 Mar 29.

Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil

We present here the draft genome sequence of the first New Delhi metallo-β-lactamase (NDM-1)-producing strain, belonging to sequence type 155 (ST155), isolated in Peru. Assembly of this draft genome resulted in 5,061,184 bp, revealing a clinically significant resistome for β-lactams, aminoglycosides, tetracyclines, phenicols, sulfonamides, trimethoprim, and fluoroquinolones.
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http://dx.doi.org/10.1128/genomeA.00199-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876490PMC
March 2018

Selective dopaminergic neurotoxicity of three heterocyclic amine subclasses in primary rat midbrain neurons.

Neurotoxicology 2018 03;65:68-84

School of Health Sciences, Purdue University, West Lafayette, IN, 47907, United States; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, United States. Electronic address:

Heterocyclic amines (HCAs) are primarily produced during high temperature meat cooking. These compounds have been intensively investigated as mutagens and carcinogens. However, converging data suggest that HCAs may also be neurotoxic and potentially relevant to neurodegenerative diseases such as Parkinson's disease (PD). The identification of new potential etiological factors is important because most PD cases are sporadic. Our group previously showed that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was selectively neurotoxic to dopaminergic neurons. However, PhIP is one of many HCAs, a class of compounds that exhibits wide structural variability. The goal of this study was to determine the neurotoxicity of the most prevalent and best studied HCAs from three subclasses: aminoimidazoaazarenes (AIA), α-carbolines, and β-carbolines. Using E17 rat primary midbrain cultures, we tested dopaminergic and non-dopaminergic neurotoxicity elicited by the following compounds: 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), PhIP, 1-methyl-9H-pyrido[3,4-b]indole (harmane), 9H-pyrido[3,4-b]indole (norharmane) and 2-amino-9H-pyrido[2,3-b]indole (AαC) at concentrations ranging from 100 nM-5 μM. All tested HCAs were selectively neurotoxic, though the dose required to elicit selective loss of dopaminergic neurons or decreases in dopaminergic neurite length was compound specific. Non-dopaminergic neurons were unaffected at all tested doses. The sensitivity (determined by threshold dose required to elicit selective neurotoxicity) appears to be unrelated to published mutagenic potency. Both AIA and α/β-carbolines produced oxidative damage, which was magnified in dopaminergic neurons vs. non-dopaminergic neurons as further evidence of selective neurotoxicity. These studies are expected to prompt clinical and mechanistic studies on the potential role of HCA exposure in PD.
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http://dx.doi.org/10.1016/j.neuro.2018.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015749PMC
March 2018

Cáncer colorrectal en los jóvenes: factores pronósticos y características clínico patológicas en un instituto del cáncer de Perú.

Rev Gastroenterol Peru 2016 Jan-Mar;36(1):35-42

Departamento de Oncología Médica. Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú.

Objective: To determine clinicopathological features and prognostic factors among young colorectal cancer (CRC) patients in a Peruvian Cancer Institute.

Methods: Data of patients 40 years or younger, admitted between January 2005 and December 2010, were analyzed.

Results: During the study period, 196 young patients with CRC were admitted. The tumor was located in the rectum, left colon and right colon in 45.9%, 28.6% and 25.5% of cases. Family history of CRC was found in 13.2% and an autosomal pattern of inheritance, in 8.6% of the cases. The most common symptoms were pain (67.9%) and bleeding (67.3%). The majority (63.1%) of colon cancer cases and more than a third (34.4%) of rectal cancer cases were diagnosed in stage III or IV. The histologic type was tubular, mucinous and signet ring cell adenocarcinoma in 73.5%, 14.8% and 8.6%, respectively. The depth of invasion was T3 in 21.4% and T4 in 53%. Nodal involvement was detected in 44.5%. Five-year overall survival (OS) was 44.3%. In the multivariate analysis, only the stage resulted an independent prognostic factor for survival.

Conclusions: CRC in Peruvian young patients is mostly sporadic. It presents more often in the distal colon or rectum and at advanced stages of the disease. Mucinous and signet ring cell carcinoma were requent histological types. Five-year OS stage by stage is similar to that reported in the literature for older patients. Stage was the only independent prognostic factor for survival.
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May 2017

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

Genet Med 2016 Apr 30;18(4):364-71. Epub 2015 Jul 30.

Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Purpose: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).

Methods: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.

Results: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.

Conclusion: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.
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http://dx.doi.org/10.1038/gim.2015.89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733433PMC
April 2016

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

BMC Med Genet 2015 Feb 25;16. Epub 2015 Feb 25.

John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.

Background: Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies.

Methods: Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families.

Results: Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families.

Conclusions: Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.
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http://dx.doi.org/10.1186/s12881-015-0149-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422282PMC
February 2015

[Adjuvant chemo radiotherapy after gastrectomy and D2 lymphadenectomy in patients with gastric cancer in the National Institute of Cancer, Lima, Peru].

Rev Gastroenterol Peru 2013 Jan-Mar;33(1):34-8

Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú.

Introduction: Adjuvant chemo radiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT0116 pivotal trial established adjuvant chemo radiation as the standard care for resected high risk adenocarcinoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standard surgery for gastric cancer.

Objective: To prove that chemo and radio therapy post gastrectomy and D2 linphadenectomy in patients' with gastric cancer is effective.

Material And Methods: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at INEN (Instituto Nacional de Enfermedades Neoplasicas) Lima-Peru between 2001 and 2006. Standard treatment at institution is D2 lymphadenectomy. Chemo radiotherapy according to INT0116 was given like adjuvant therapy. Survivalcurves were calculated according to Kaplan-Meier method and compared with log-rank test.

Results: 84 patients were included 60.7% male and 39.3% female. Mean age was 49.5 years old. The pathologic stages were T1-T2 (15.5%), T3- T4 (84.5%), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survival was 23.9%. However when we analyzed by subgroups the overall survival, was in group N1 (66.7%) and in group N2 (58.9%) and N3 (18.3%) and 3 years DFS by subgroups were N1 (100%), N2 (51.9%) and N3 (16.3%).

Conclusions: Adjuvant chemo radiotherapy decreased risk of death and relapse to three years mainly in patients with node positive N1-N2, who underwent curative resection with D2 lymphadenectomy, but recurrence was most frequent in N3 node positive, maybe is necessary improve the chemotherapy in this group of patients for decrease the rate of relapse.
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April 2014

The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study.

BMC Cancer 2009 Nov 20;9:406. Epub 2009 Nov 20.

Molecular Oncology Group, Elche University Hospital, Camino Almazara 11, 03203 Elche, Spain.

Background: The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage.

Methods: We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR.

Results: The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005). No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023), but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years.

Conclusion: Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.
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http://dx.doi.org/10.1186/1471-2407-9-406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784798PMC
November 2009

The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study.

BMC Cancer 2009 Jun 18;9:193. Epub 2009 Jun 18.

Molecular Oncology Group, Elche University Hospital, Camino Almazara 11, Elche, Spain.

Background: TGF-beta receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-beta receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population.

Methods: The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility.

Results: There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799-1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306-2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system.Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with mutations that cause allele-specific expression, as was recently suggested.

Conclusion: Our results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population.
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http://dx.doi.org/10.1186/1471-2407-9-193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708189PMC
June 2009