The saga of the many studies wrongly associating mitochondrial DNA with breast cancer

Background A large body of genetic research has focused on the potential role that mitochondrial DNA (mtDNA) variants might play on the predisposition to common and complex (multi-factorial) diseases. It has been argued however that many of these studies could be inconclusive due to artifacts related to genotyping errors or inadequate design. Methods Analyses of the data published in case–control breast cancer association studies have been performed using a phylogenetic-based approach. Variation observed in these studies has been interpreted in the light of data available on public resources, which now include over >27,000 complete mitochondrial sequences and the worldwide phylogeny determined by these mitogenomes. Complementary analyses were carried out using public datasets of partial mtDNA sequences, mainly corresponding to control-region segments. Results By way of example, we show here another kind of fallacy in these medical studies, namely, the phenomenon of SNP-SNP interaction wrongly applied to haploid data in a breast cancer study. We also reassessed the mutually conflicting studies suggesting some functional role of the non-synonymous polymorphism m.10398A > G (ND3 subunit of mitochondrial complex I) in breast cancer. In some studies, control groups were employed that showed an extremely odd haplogroup frequency spectrum compared to comparable information from much larger databases. Moreover, the use of inappropriate statistics signaled spurious “significance” in several instances. Conclusions Every case–control study should come under scrutiny in regard to the plausibility of the control-group data presented and appropriateness of the statistical methods employed; and this is best done before potential publication.AS has been supported by grants from the “Ministerio de Ciencia e Innovación” (SAF2011-26983) and from the Plan Galego IDT, Xunta de Galicia (EM 2012/045)S

Diagnostic yield of sentinel lymph node biopsy in oral squamous cell carcinoma T1/T2-N0: systematic review and meta-analysis

The objective of this study was to conduct a systematic review and meta-analysis on the efficacy of sentinel lymph node biopsy (SLNB) in T1/T2-N0 oral squamous cell carcinoma (OSCC). A systematic review of the literature on SLNB until March 2019 was conducted. The review was organized according to the PRISMA protocol, considering the following PICO (population, intervention, comparison, outcome) question: What is the sensitivity of sentinel lymph node biopsy in OSCC? ‘P’ was patients with head and neck squamous cell carcinoma T1/2-N0; ‘I’ was SLNB; ‘C’ was neck treated with elective neck dissection and haematoxylin–eosin histopathology; ‘O’ was sensitivity and specificity. A meta-analysis and meta-regression were performed on the selected studies. The sensitivity of SLNB was up to 88% (95% confidence interval (CI) 72–96%) and specificity was up to 99% (95% CI 96–100%). The area under the summary receiver operating characteristic curve was 0.99 (95% CI 0.98–1.00). In the four studies where immunohistochemistry was performed, both the sensitivity and specificity were higher than in the studies without immunohistochemistry: 93% (95% CI 88–97%) and 98% (95% CI 96–100%), respectively. In conclusion, SLNB is an effective technique for treating patients with some types of stage T1/2-N0 OSCC. Some parameters such as immunohistochemistry could determine the level of diagnostic accuracyS

Th17-Related Genes and Celiac Disease Susceptibility

Th17 cells are known to be involved in several autoimmune or inflammatory diseases. In celiac disease (CD), recent studies suggest an implication of those cells in disease pathogenesis. We aimed at studying the role of genes relevant for the Th17 immune response in CD susceptibility. A total of 101 single nucleotide polymorphisms (SNPs), mainly selected to cover most of the variability present in 16 Th17-related genes (IL23R, RORC, IL6R, IL17A, IL17F, CCR6, IL6, JAK2, TNFSF15, IL23A, IL22, STAT3, TBX21, SOCS3, IL12RB1 and IL17RA), were genotyped in 735 CD patients and 549 ethnically matched healthy controls. Case-control comparisons for each SNP and for the haplotypes resulting from the SNPs studied in each gene were performed using chi-square tests. Gene-gene interactions were also evaluated following different methodological approaches. No significant results emerged after performing the appropriate statistical corrections. Our results seem to discard a relevant role of Th17 cells on CD risk

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

The ‘Pokemon’ () Gene: No Evidence of Association with Sporadic Breast Cancer

It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7 , including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson's chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association