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XPD codon 751 polymorphism, metabolism genes, smoking, and bladder cancer risk
Mariana C Stern1, Laura R Johnson, Douglas A Bell
1Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis and the National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, 27709, USA.
Summary
Cigarette smoking significantly increases bladder cancer risk. Specific genetic variations in XPD, NAT1, and NAT2 genes may influence this risk, particularly in combination with smoking habits.
Area of Science:
- Genetics
- Cancer Research
- Molecular Epidemiology
Background:
- Cigarette smoking is a primary risk factor for bladder cancer.
- Aryl-amines in smoke are metabolized by NAT1 and NAT2 enzymes, potentially leading to DNA damage.
- Nucleotide excision repair, involving XPD protein, repairs DNA adducts.
Purpose of the Study:
- To investigate the association between XPD codon 751 polymorphism and bladder cancer risk.
- To examine if NAT1 and NAT2 gene variants modify the effect of XPD polymorphism on smoking-associated bladder cancer risk.
Main Methods:
- Genotyping for XPD codon 751 polymorphism in 228 bladder cancer cases and 210 controls.
- Utilized existing NAT1 and NAT2 genotype data for the same individuals.
- Statistical analysis to assess genotype-risk associations and gene-gene-environment interactions.
Main Results:
- The XPD codon 751 Gln/Gln genotype showed a slight decrease in bladder cancer risk.
- Smokers with XPD Lys/Lys or Lys/Gln genotypes had double the risk compared to Gln/Gln smokers (P=0.03).
- Little evidence for a three-way interaction between XPD genotype, smoking, and NAT1/NAT2 genotype.
Conclusions:
- The XPD codon 751 polymorphism may influence bladder cancer risk, especially in smokers.
- While NAT1/NAT2 and XPD genotypes interact, a significant three-way interaction with smoking was not observed.
- Further research may clarify the complex interplay of genetic factors and smoking in bladder carcinogenesis.