DNA repair polymorphisms and cancer risk in non-smokers in a cohort study

Abstract

Environmental carcinogens contained in air pollution, such as polycyclic aromatic hydrocarbons, aromatic amines or N-nitroso compounds, predominantly form DNA adducts but can also generate interstrand cross-links and reactive oxygen species. If unrepaired, such lesions increase the risk of somatic mutations and cancer. Our study investigated the relationships between 22 polymorphisms (and their haplotypes) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases (bladder cancer, 131; lung cancer, 134; oral-pharyngeal cancer, 41; laryngeal cancer, 47; leukaemia, 179; death from emphysema and chronic obstructive pulmonary disease, 84). The design was a case-control study nested within a prospective investigation. Among the many comparisons, few polymorphisms were associated with the diseases at the univariate analysis: XRCC1-399 Gln/Gln variant homozygotes [odds ratios (OR) = 2.20, 95% confidence intervals (CI) = 1.16-4.17] and XRCC3-241 Met/Met homozygotes (OR = 0.51, 95% CI = 0.27-0.96) and leukaemia. The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1-399Gln/Gln in lung cancer (OR = 0.22, 95% CI = 0.05-0.98), and confirmed an opposite effect (OR = 2.47, 95% CI = 1.02-6.02) in the leukaemia group. Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia (OR = 1.28, 95% CI = 1.02-1.61), bladder cancer (OR = 1.38, 95% CI = 1.06-1.79) and possibly other cancer risks. Further investigations of the combined effects of polymorphisms within these DNA repair genes, smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process.

Lack of Influence of an XRCC3 Gene Polymorphism on Oral Cancer Susceptibility: Meta-analysis

“…This change may influence their protein activity, resulting in differences of individual DNA repair capacity (DRC) that may affect the susceptibility of oral cancer. Growing number of studies have been done to examine the relationship between this SNP and the risks of oral cancer (Benhamou et al, 2004;Majumder et al, 2005;Matullo et al, 2006;Kietthubthew et al, 2006;Yang et al, 2008;Yen et al, 2008;Dos Reis et al, 2013). However, the results are inconclusive.…”

“…XRCC3 gene is involved in the repair of DNA double-strand breaks (DSB), which is important to prevent chromosomal fragmentation, translocations and deletions (Kanaar et al, 1998). To date, there are studies reporting the association between polymorphisms of XRCC3 codon 241 with oral cancer risk but these published data were contradictory (Benhamou et al, 2004;Majumder et al, 2005;Matullo et al, 2006;Kietthubthew et al, 2006;Yang et al, 2008;Yen et al, 2008;Dos Reis et al, 2013). Until now, there was no meta-analysis or systematic review on the risk of oral cancer with XRCC3 polymorphism.…”

Genetic polymorphisms in double-strand break DNA repair genes associated with risk of oral premalignant lesions

“…This variant allele has also been reported to confer a significantly decreased susceptibility to bladder (35), invasive ovarian (21), and upper aerodigestive (37) cancers. However, a few studies have shown no such association with cancer (37)(38)(39)(40). Factors such as study design, sample size, cancer sites, population heterogeneity, and the biological complexity of low-penetrance cancer susceptibility genes may explain the observed discrepancies.…”

The XRCC3 Thr241Met Polymorphism Influences Glioma Risk - A Meta-analysis

“…Therefore, XRCC3 polymorphism has received widespread attention, and many meta-analyses were reported to explore the relationship between the polymorphism and human cancers (Kiyohara et al, 2006;Saadat et al, 2009;Jacobs et al, 2012). Matullo and colleagues (Matullo et al, 2006) have realized that XRCC3 Thr241Met (rs861539) polymorphism could influence the capacity of DNA repair, and came to the conclusion that the XRCC3 Thr241Met polymorphism may be associated with cancer risks. However, the association strength of XRCC3 Thr241Met in the field of glioma susceptibility remains conflicting and is eager to be discovered.…”