ABSTRACT
El sistema de reparación del daño al DNA por escisión de nucleótidos (NER), es un sistema de reparación altamente versátil y sofisticado, que contrarresta los efectos deletéreos de las lesiones en el DNA, incluyendo la radiación ultravioleta...
Subject(s)
Humans , DNA , Skin Diseases, Genetic , Transcription Factor TFIIHABSTRACT
El tipo histológico más común de cáncer de tiroides es el cáncer papilar, comprende aproximadamente el 90% de la incidencia de cancer de tiroides. Alteraciones genéticas que incluyen reestructuraciones cromosómicas y mutaciones puntuales están implicadas en su patogénesis. las reestructuraciones cromosómicas incluyen reordenaciones del gen RET y del gen TRK, además de mutaciones puntuales en el gen BRAF y el gen RAS. Estas alteraciones genéticas que raramente ocurren simultaneamente en el tumor, producen señalizaciones aberrantes en la vía MAPK (mitogen-activated protón kinase). El desarrollo de nuevas modalidades terapéuticas en el cáncer de tiroides es crucial en aquellos tumores que han probado ser resistentes a la terapia con yodo radioactivo y a la supresión de hormona estimulante del tiroides.
Subject(s)
Humans , Carcinoma, Papillary/genetics , Iodine Radioisotopes/therapeutic use , Thyroid Diseases , Thyrotropin/therapeutic useABSTRACT
Several genes directly related to thyroid cancer development have been described; nevertheless, the genetic pathways of this tumorigenesis process are unknown. Together with environmental factors, susceptibility genes could have an important role in thyroid cancer. Our previous studies suggest that the chromosome 1p12-13 is related to thyroid cancer incidence. Here, we extend the analysis with a case-control association study in a Spanish population. Thus, six single-nucleotide polymorphisms were genotyped, covering 2.4 Mb of the 1p12-13 region. A statistically significant association between thyroid cancer incidence and the rs2145418 and rs4658973 polymorphisms was found (P < 0.0001). No association was detected for the other four polymorphisms studied. The rs2145418 marker showed a significant odds ratio of 5.0 [95% confidence interval (95% CI), 2.85-8.83] and 9.2 (95% CI, 4.50-21.6) for heterozygous and homozygous G-variant alleles, respectively. For rs4658973, the odds ratios were 0.40 (95% CI, 0.26-0.62) and 0.07 (95% CI, 0.03-0.18) for heterozygous and homozygous G-variant alleles, respectively. These markers map into the 1p12 region, and no linkage disequilibrium was found between them, indicating an independent relation of these polymorphisms with thyroid cancer susceptibility. Our data provide evidence of a strong association of the chromosome 1p12 with thyroid cancer risk, and it is the first study describing susceptibility loci for thyroid cancer in this region.
