Background: DNA helicases maintain genome stability, and their deficiency is associated
with disorders resembling premature aging as well as contributes to carcinogenesis. Their
functions are determined by the respective genes encoding nucleotide excision repair initiating
proteins, e.g. XPD and CSB.
Objective: The present study aimed to investigate the influence of genetic variations in
ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and
developing age-related bladder cancer focusing on homozygous wild type alleles.
Method: The allelic variants were identified in 354 clinically healthy controls and 418 bladder
cancer patients using the PCR-RFLP method.
Results: The age-depended increase in frequencies of homozygous carriers of wild-type XPD
312Asp and XPD 751Lys alleles was observed among controls, especially among subjects over 80
years (r = 0.67, p = 0.012). The statistically significant correlation was also found between the
frequency of homozygous wild type alleles at all tested loci and age in healthy population over 60
years (r = 0.35, p = 0.046) suggesting the relationship between lifespan and longevity, on one hand,
and normal functioning of these genes and their products, on the other hand. Homozygous carriers
of wild type alleles were less susceptible to bladder cancer, tumor invasion, increase in grade of
malignancy and recurrence, but their effects were specific with respect to clinicopathological and
Conclusion: Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties
were shown to affect human lifespan, risk of developing bladder cancer, its progression and
recurrence under certain conditions.