An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Amaurosis cortical aguda secundaria a preeclampsia

La amaurosis cortical aguda es una complicacióndramática y poco común de la preeclampsia. Se presentaun caso de paciente de 29 años con diagnóstico depreeclampsia grave quien describió deterioro de la agudezavisual repentino en el puerperio inmediato. El fondo deojo fue normal. La paciente identificaba la luz intensa.Las pupilas estaban reactivas y no se observó la presenciade nistagmo. Se le realizó una resonancia magnéticacuyos resultados fueron normales, por lo que se realizó eldiagnóstico de amaurosis cortical aguda.Palabras clave: Amaurosis cortical aguda; Preeclampsia;Embarazo.SUMMARYAcute cortical blindness is an uncommon and dramaticcomplication of preeclampsia. We present a case of a 29years-old patient with diagnosis of severe preeclampsia whodescribed a sudden loss of visual acuity during immediatepuerperium. Fundi were normal. Pupils were reactiveand there was no nystagmus A magnetic resonance wereperformed with normal results, be cause diagnosis of acutecortical blindness was done.Key words: Acute cortical blindness. Preeclampsia.Pregnancy

Macro - microcirugía tubárica

Se presenta la experiencia quirúrgica de un lapso de 21 años en la práctica de recanalización tubárica de trompas de Falopio, obstruidas por procesos inflamatorios o por esterilizaciones quirúrgicas.It displays the surgical experience in 21 years on oviduct reconstruction, blocking by inflammatory process or by surgical sterilization, of thirty patients of the gynecological services in the Maternidad “Concepcion Palacios”, showing the pre and postsurgical methods