Genetic susceptibility to bladder cancer with an emphasis on gene-gene and gene-environmental interactions.
OBJECTIVE
The present article reviews recent reports on molecular epidemiological studies for exploring susceptibility genes for bladder cancer, with particular focus on gene-gene and gene-environmental interactions.


RESULTS
Recent large case-control studies and meta-analyses have confirmed that N-acetyl transferase2 slow acetylator and glutathione S-transferase Mu null genotype were modest susceptibility factors for bladder cancer, with probable interactions between N-acetyl transferase2 slow acetylator and smoking. Several interesting studies using a multigenic pathway-based genotyping approach and novel statistical tools showed significant interactions among potential functional single nucleotide polymorphisms in DNA repair pathway genes and smoking and gene-diet interaction; however, the resultant interactions warrant validation.


CONCLUSIONS
Previous studies using a candidate gene approach have not only identified a few bladder cancer susceptibility loci but also produced a large number of false positive results. A multigenic pathway-based approach may identify gene-gene and gene-environment interactions and increase predictive power. Several statistical tools have been applied to identify gene-gene and gene-environment interactions, but future efforts should be directed toward integrating results obtained from different statistical tools and validating resultant interactions from different studies.
Horikawa
Yohei
Y
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gu
Jian
J
Wu
Xifeng
X
D020022:Genetic Predisposition to Disease; D006801:Humans; D017720:Molecular Epidemiology; D020412:Multifactorial Inheritance; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*