Asociación del cáncer colorrectal con variantes genéticas y rutas metabólicas relacionadas con NRF = Association of colorectal cancer with NRF related genetic variants and metabolic pahtways

235 p.Introducción: El cáncer colorrectal es un tipo de cáncer multietápico y multifactorial influenciado por una gran cantidad de elementos ambientales y genéticos. La Biogenésis Mitocondrial, haciendo mención especial a los genes NRF1 y NRF2, podría estar relacionada con este tipo de cáncer ya que estos genes controlan procesos como la regulación de los ARE, la homeostasis y la activación de genes involucrados en la función mitocondrial, coordinando la expresión de genes nucleares y mitocondriales. Objetivo: Analizar la relación entre los genes NRF1 y NRF2 y el CCR e identificar variantes genéticas y rutas metabólicas relacionadas con estos genes asociadas con el riesgo de CCR. Metodología: Se llevó una revisión sistemática cualitativa para analizar el papel de NRF1 y NRF2 en el CCR. A partir de los datos del estudio MCC-Spain, un estudio multicaso-control, se realizó un análisis de SNP a SNP y un análisis de pathways en el que se emplearon tres técnicas diferentes: SNP Ratio Test, fast Gene Set Enrichment Score y Pathway of Distinction Analysis. Resultados: De acuerdo a las evidencias científicas publicadas, se podría afirmar que existe relación entre la expresión/actividad alterada de NRF2 y el cáncer colorrectal, de tal manera que tanto una sobreexpresión como una inhibición del mismo se relaciona con este tipo de cáncer. El genotipo gT del SNP rs12706898 se detectó como un factor de riesgo para desarrollar cáncer de colon derecho en hombres. Mediante la técnica de PoDA, se detectaron 6 rutas metabólicas relacionadas con NRF1 y NRF2 cuya alteración podría estar relacionada con el cáncer colorrectal: la ruta de IBD, la ruta de las MAP Kinasas, la ruta de señalización NFKβ, la ruta de señalización PI3K-AKT, la ruta de los transportadores ABC y la ruta de la biogénesis mitocondrial. Conclusión: La presencia de SNPs en genes de rutas metabólicas relacionadas con NRF1 y NRF2 se asocia con una mayor probabilidad de sufrir CCR según los resultados obtenidos mediante la técnica PoDA

Alterations in PGC1[alfa] expression levels are involved in colorectal cancer risk: a qualitative systematic review

Background: Colorectal cancer (CRC) is a major global public health problem and the second leading cause of cancer-related death. Mitochondrial dysfunction has long been suspected to be involved in this type of tumorigenesis, as supported by an accumulating body of research evidence. However, little is known about how mitochondrial alterations contribute to tumorigenesis. Mitochondrial biogenesis is a fundamental cellular process required to maintain functional mitochondria and as an adaptive mechanism in response to changing energy requirements. Mitochondrial biogenesis is regulated by peroxisome proliferator-activated receptor gamma coactivator 1-? (PPARGC1A or PGC1?). In this paper, we report a systematic review to summarize current evidence on the role of PGC1? in the initiation and progression of CRC. The aim is to provide a basis for more comprehensive research. Methods: The literature search, data extraction and quality assessment were performed according to the document Guidance on the Conduct of Narrative Synthesis in Systematic Reviews and the PRISMA declaration. Results: The studies included in this review aimed to evaluate whether increased or decreased PGC1? expression affects the development of CRC. Each article proposes a possible molecular mechanism of action and we create two concept maps. Conclusion: Our systematic review indicates that altered expression of PGC1? modifies CRC risk. Most studies showed that overexpression of this gene increases CRC risk, while some studies indicated that lower than normal expression levels could increase CRC risk. Thus, various authors propose PGC1? as a good candidate molecular target for cancer therapy. Reducing expression of this gene could help to reduce risk or progression of CRC

PoDA algorithm: Predictive pathways in colorectal cancer

SOCO’17-CISIS’17-ICEUTE’17 (León. 2017

A multiregressive approach for SNPs identification in prostate cancer

SOCO 2017, ICEUTE 2017, CISIS 2017 (León. 2017

Additional file 1: Table S1. of Alterations in PGC1α expression levels are involved in colorectal cancer risk: a qualitative systematic review

Reasons for exclusion of 22 articles according to abstract and full-text. Table that describes the reasons for exclusion of the selected articles in the first review. Table S2. Full details of the key characteristics of the selected studies. Table that describes the details of the selected articles. (PDF 245 kb

Validating a breast cancer score in Spanish women. The MCC-Spain study

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations

Validating a breast cancer score in Spanish women: The MCC-Spain study

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendation

Agreement among mediterranean diet pattern adherence indexes: MCC-Spain Study

There are many different methods used to measure the degree of adherence to a Mediterranean diet (MD), limiting comparison and interpretation of their results. The concordance between different methodologies has been questioned and their evaluation recommended. The aim of this study was to evaluate the agreement among five indexes that measure adherence to a Mediterranean dietary pattern. The study population included healthy adults selected in the Multi-Case Control Spain (MCC-Spain) study recruited in 12 provinces. A total of 3640 controls were matched to cases by age and sex. To reach the aim, the following scores of adherence to a Mediterranean dietary pattern were calculated: Mediterranean diet score (MDS), alternative Mediterranean diet (aMED), relative Mediterranean diet (rMED), dietary score (DS) and literature-based adherence score (LBAS). The relative frequency of subjects with a high level of adherence to a MD varied from 22% (aMED index) to 37.2% (DS index). Similarly, a high variability was observed for the prevalence of a low level of MD: from 24% (rMED) to 38.4% (aMED). The correlation among MDS, aMED and rMED indexes was moderate, except for MDS and aMED with a high coefficient of correlation 0.75 (95% CI 0.74⁻0.77). The Cohen's Kappa coefficient among indexes showed a moderate⁻fair concordance, except for MDS and aMED with a 0.56 (95% CI 0.55⁻0.59) and 0.67 (95% CI 0.66⁻0.68) using linear and quadratic weighting, respectively. The existing MD adherence indexes measured the same, although they were based on different constructing algorithms and varied in the food groups included, leading to a different classification of subjects. Therefore, concordance between these indexes was moderate or low