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Polymorphisms in XPD exons 10 and 23 and bladder cancer risk
Matthew B Schabath1, George L Delclos, H Barton Grossman
1Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Unit 189, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Summary
The xeroderma pigmentosum complementation group D (XPD) gene variants are linked to increased bladder cancer risk in women and smokers. These findings highlight potential gender and smoking interactions with XPD genotypes in bladder cancer development.
Area of Science:
- Genetics and Cancer Epidemiology
- Molecular Epidemiology of DNA Repair
Background:
- The xeroderma pigmentosum complementation group D (XPD) gene is involved in nucleotide excision repair.
- Previous studies on XPD's role in cancer risk have yielded conflicting results.
- Investigating XPD polymorphisms may clarify its association with cancer susceptibility.
Purpose of the Study:
- To investigate the association between XPD gene polymorphisms (Asp312Asn and Lys751Gln) and bladder cancer risk.
- To explore potential gender-specific and smoking-related interactions with XPD genotypes in bladder cancer.
Main Methods:
- Case-control study involving 505 bladder cancer cases and 486 healthy controls.
- Genotyping of XPD exon 10 (Asp312Asn) and exon 23 (Lys751Gln) polymorphisms.
- Statistical analysis adjusted for age, sex, ethnicity, and smoking status, including interaction analyses.
Main Results:
- No overall association was found between XPD genotypes and bladder cancer risk.
- A significant gender-specific effect was observed, with increased risk in women carrying variant genotypes for both exons.
- Statistically significant gene-smoking interactions indicated elevated bladder cancer risk for smokers with variant XPD alleles, particularly heavy smokers.
Conclusions:
- While no main effects of XPD genotypes were detected, variant alleles were associated with increased bladder cancer risk in women and smokers.
- Significant interactions were noted for the XPD exon 23 polymorphism with gender and smoking.
- These novel findings warrant cautious interpretation and require confirmation in larger prospective studies.