Genomics and pharmacogenomics of colorectal cancer

  1. Fernández Rozadilla, Ceres
Supervised by:
  1. Clara María Ruiz Ponte Director
  2. Ángel Carracedo Álvarez Tutor

Defence university: Universidade de Santiago de Compostela

Fecha de defensa: 22 July 2011

Committee:
  1. Fernando Domínguez Puente Chair
  2. Anxo Vidal Figueroa Secretary
  3. Montserrat Baiget Bastús Committee member
  4. S. Castellví-Bel Committee member
  5. Jean-Baptiste Cazier Committee member

Type: Thesis

Teseo: 313679 DIALNET lock_openMINERVA editor

Abstract

SUMMARY: GENOMICS AND PHARMACOGENOMICS OF COLORECTAL CANCER. Heritability in colorectal cancer (CRC) predisposition has been estimated to be around 35% by twin studies. Although ¿ 5% of this proportion may be explained by high-penetrance mutations, and an additional 7% is thought to be due to the presence of a combination of some of the already-described 16 susceptibility SNPs, there is still a significant fraction of CRC susceptibility that remains unexplained. On the other hand, there is also considerable variation in the way CRC patients respond to chemotherapy. Besides, the fact that most drugs used in CRC treatment have narrow therapeutic ranges results in the frequent development of adverse drug reactions (ADRs). Hence, the identification of the genetic variation modulating this outcome would be most helpful in both the individualisation of the treatment and the reduction of health costs. Thus, this PhD work has had two main aims: the search for new CRC susceptibility variants that could help explain at least part of the missing heritability, andd the analysis of the genetic variation underlying the differences in toxic responses of CRC patients treated with chemotherapy.