scholarly journals Gene-environment interaction of genome-wide association study-identified susceptibility loci and meat-cooking mutagens in the etiology of renal cell carcinoma

Cancer ◽  
2015 ◽  
Vol 122 (1) ◽  
pp. 108-115 ◽  
Author(s):  
Stephanie C. Melkonian ◽  
Carrie R. Daniel ◽  
Yuanqing Ye ◽  
Nizar M. Tannir ◽  
Jose A. Karam ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Renal Cell ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Environment Interaction ◽  
Susceptibility Loci ◽  
Gene Environment Interaction ◽  
Meat Cooking ◽  
Gene Environment ◽  
Genome Wide

scholarly journals Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3

2010 ◽  
Vol 43 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Mark P Purdue ◽  
Mattias Johansson ◽  
Diana Zelenika ◽  
Jorge R Toro ◽  
Ghislaine Scelo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Association Study ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide

scholarly journals CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children’s Oncology Group Genome-Wide Association Study

2016 ◽  
Vol 34 (8) ◽  
pp. 863-870 ◽  
Author(s):  
Xuexia Wang ◽  
Can-Lan Sun ◽  
Adolfo Quiñones-Lombraña ◽  
Purnima Singh ◽  
Wendy Landier ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Dose Dependent

Purpose Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk. Methods A genome-wide association study was conducted in childhood cancer survivors with and without cardiomyopathy (cases and controls, respectively). Single-nucleotide polymorphisms (SNPs) that surpassed a prespecified threshold for statistical significance were independently replicated. The possible mechanistic significance of validated SNP(s) was sought by using healthy heart samples. Results No SNP was marginally associated with cardiomyopathy. However, SNP rs1786814 on the CELF4 gene passed the significance cutoff for gene-environment interaction (Pge = 1.14 × 10−5). Multivariable analyses adjusted for age at cancer diagnosis, sex, anthracycline dose, and chest radiation revealed that, among patients with the A allele, cardiomyopathy was infrequent and not dose related. However, among those exposed to greater than 300 mg/m2 of anthracyclines, the rs1786814 GG genotype conferred a 10.2-fold (95% CI, 3.8- to 27.3-fold; P < .001) increased risk of cardiomyopathy compared with those who had GA/AA genotypes and anthracycline exposure of 300 mg/m2 or less. This gene-environment interaction was successfully replicated in an independent set of anthracycline-related cardiomyopathy. CUG-BP and ETR-3-like factor proteins control developmentally regulated splicing of TNNT2, the gene that encodes for cardiac troponin T (cTnT), a biomarker of myocardial injury. Coexistence of more than one cTnT variant results in a temporally split myofilament response to calcium, which causes decreased contractility. Analysis of TNNT2 splicing variants in healthy human hearts suggested an association between the rs1786814 GG genotype and coexistence of more than one TNNT2 splicing variant (90.5% GG v 41.7% GA/AA; P = .005). Conclusion We report a modifying effect of a polymorphism of CELF4 (rs1786814) on the dose-dependent association between anthracyclines and cardiomyopathy, which possibly occurs through a pathway that involves the expression of abnormally spliced TNNT2 variants.

Sign in / Sign up

Export Citation Format

Share Document