DNA adduct levels and DNA repair polymorphisms in traffic-exposed workers and a general population sample

Abstract

Peripheral blood DNA adducts have been considered an acceptable surrogate for target tissues and possibly predictive of cancer risk. A group of 114 workers exposed to traffic pollution and a random sample of 100 residents were drawn from the EPIC cohort in Florence, a population recently shown to present increased DNA adduct levels (Palli et al., Int J Cancer 2000;87:444 -51). DNA bulky adducts and 3 DNA repair gene polymorphisms were analyzed in peripheral leukocytes donated at enrollment, by using 32 P-postlabeling and PCR methods, respectively. Adduct levels were significantly higher for traffic workers among never smokers (p ‫؍‬ 0.03) and light current smokers (p ‫؍‬ 0.003). In both groups, urban residents tended to show higher levels than those living in suburban areas, and a seasonal trend emerged with adduct levels being highest in summer and lowest in winter. Traffic workers with at least 1 variant allele for XPD-Lys751Gln polymorphism had significantly higher levels in comparison to workers with 2 common alleles (p ‫؍‬ 0.02). A multivariate analysis (after adjustment for age, season, area of residence, smoking, XPD-Lys751Gln genotype and antioxidant intake) showed a significant 2-fold association between occupational exposure and higher levels of adducts (odds ratio 2.1; 95% confidence interval 1.1-4.2), in agreement with recent pooled estimates of increased lung cancer risk for similar job titles. Our results suggest that traffic workers and the general population in Florence are exposed to high levels of genotoxic agents related to vehicle emissions. Photochemical pollution in warmer months might be responsible for the seasonal trend of genotoxic damage in this Mediterranean urbanized area.

Effect of dna repair gene polymorphisms on BPDE‐DNA adducts in human lymphocytes

“…[27][28][29] Various explanations are possible for the divergence between these studies and ours. The controversial results might depend partly on differences in the type of DNA damage detected when compared to the specific BPDE-DNA adduct we have measured.…”

Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

“…Even though devoid of any known enzymatic activity, XRCC1 is thought to act as a scaffold protein, play a coordinating role for consecutive stages of the BER system (Ladiges, 2006), The XRCC1 Arg399Gln polymorphism is located within the XRCC1 BRCA1 carboxyl-terminal domain (BRCT I) and is hypothesized to have functional significance because it is located within a well-conserved region and encodes a nonconservative amino acid change. However, studies examining its relation with markers of DNA damage or DNA repair function have yielded mixed results, with some studies showing a positive relation (Duell et al, 2002;Qu and Morimoto, 2005) and others observing no relation with the variants (Palli et al, 2001;Pastorelli et al, 2002;Tuimala et al, 2002;Hu et al, 2005;Leng et al, 2005;Laantri et al, 2011 ). In present study we found homozygous variants of XRCC1 Arg399Gln had observably associations with NPC risk.…”

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer

“…A few previous studies reported that the 399Gln allele was associated with a higher level of DNA adducts and glycophorin A mutations (Lunn et al, 1999;Matullo et al, 2001a, b), increased sister chromatin exchange frequencies (Duell et al, 2000), or higher sensitivity to ionizing radiation and chemical mutagens (Hu et al, 2001;Wang et al, 2003a, b). However, conflicting results also exist, showing no association between the 399Arg>Gln polymorphism and DNA adduct levels (Matullo et al, 2001a, b;Palli et al, 2001). The reason for this inconsistency may be the result of some study design issues.…”