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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 lifestyle characteristics., 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Tobacco smoke and air pollutants contain carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and tobacco specific nitrosamines (TSNA), that are substrates of metabolizing enzymes generating reactive metabolites that can bind to DNA. Variation in the activity of these enzymes may modify the extent to which these metabolites can interact with DNA. We compared the levels of bulky DNA adducts in blood leukocytes from 93 volunteers living in Mexico City with the presence of 13 single nucleotide polymorphisms (SNPs) in genes related to PAH and TSNA metabolism (AhR rs2044853, CYP1A1 rs1048943, CYP1A1 rs1048943, CYP1A1 rs1799814, EPHX1 rs1051740, EPHX1 rs2234922, GSTM1 null, GSTT1 null and GSTP1 rs947894), DNA repair (XRCC1 rs25487, ERCC2 rs13181 and MGMT rs12917) and cell cycle (TP53 rs1042522). (32)P-postlabeling analysis was used to quantify bulky DNA adduct formation. Genotyping was performed using PCR-RFLP. The mean levels of bulky DNA adducts were 8.51±3.66 adducts/10(8) nucleotides (nt) in smokers and 8.38±3.59 adducts/10(8) nt in non-smokers, being the difference not statistically significant. Without taking into account the smoking status, GSTM1 null individuals had a marginally significant lower adduct levels compared with GSTM1 volunteers (p=0.0433) and individuals heterozygous for MGMT Leu/Phe had a higher level of bulky adducts than those who were homozygous wild type (p=0.0170). A multiple regression analysis model showed a significant association between the GSTM1 (deletion) and MGMT rs12917 (Phe/Phe) haplotype and the formation of DNA adducts in smokers (R(2)=0.2401, p=0.0215). The presence of these variants conferred a greater risk for higher adduct levels in this Mexican population., (Copyright © 2013 Elsevier B.V. All rights reserved.)