作者: Ana Martinez-Canto , Adela Castillejo , Trinidad Mata-Balaguer , Maria-Isabel Castillejo , Eva Hernandez-Illan
DOI: 10.1371/JOURNAL.PONE.0030812
关键词: Genetic predisposition 、 Haplotype 、 Germline mutation 、 Colorectal cancer 、 Genetic association 、 Genetics 、 Allele 、 Locus (genetics) 、 Case-control study 、 Biology
摘要: In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% cases. A considerable proportion sporadic tumors could be explained by the coinheritance multiple low-penetrance variants, some which are common. We assessed to CRC conferred genetic variants at TGFBR1 locus. analyzed 14 polymorphisms and allele-specific expression (ASE) in 1025 individuals from Spanish population. case-control study was undertaken with 504 controls 521 patients CRC. Fourteen located locus were genotyped iPLEX Gold (MassARRAY-Sequenom) technology. Descriptive analyses haplotypes association studies performed SNPator workpackage. No relevant associations detected between individual or The TGFBR1*9A/6A polymorphism used ASE analysis. Heterozygous fragment analysis using cDNA normal tissue. relative level allelic extrapolated a standard curve. cutoff value calculated Youden's index. found 25.4% 16.4% controls. Considering both bimodal continuous types distribution, no significant differences values identified. Interestingly, combined occurrence revealed that ASE-positive carrying one most common (H2: 20.7%) showed remarkable (RR: 5.25; 95% CI: 2.547–5.250; p<0.001) synergy factor 3.7. our study, 54.1% cases attributable H2 haplotype ASE. These results support hypothesis architecture genes, rather than polymorphisms, more accurately defines risk.