Open AccessJournal Article
Modulation of Nucleotide Excision Repair Capacity by XPD Polymorphisms in Lung Cancer Patients
Margaret R. Spitz,Xifeng Wu,Yunfei Wang,Li E. Wang,Sanjay Shete,Christopher I. Amos,Zhaozheng Guo,Lei Lei,Harvey W. Mohrenweiser,Qingyi Wei +9 more
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TLDR
The results suggest that the two XPD polymorphisms have a modulating effect on DRC, especially in the cases, and the pattern was less evident among the controls, although there was a nonsignificant 41% increase in the risk of suboptimal DRC for controls who were homozygous at either locus.Abstract:
Sequence variations have been identified in a number of DNA repair
genes, including XPD, but the effect of these
polymorphisms on DNA repair capacity (DRC) is uncertain. We therefore
examined XPD polymorphisms at Lys751Gln and
Asp312Asn in 341 white lung cancer cases and 360 age-,
sex-, ethnicity-, and smoking-matched controls accrued in a
hospital-based molecular epidemiological study of susceptibility
markers for lung cancer. As previously reported, DRC was statistically
significantly lower in the cases than in the controls (7.8%
versus 9.5%; P < 0.001),
which represents an average 18% reduction among the cases. The
variant Lys751Gln and Asp312Asn allele
frequencies were 0.36 and 0.29, respectively, for the cases and 0.33
and 0.27, respectively, for the controls. For subjects homozygous for
the variant genotype at either locus, the adjusted odds ratio [95%
confidence interval (CI)] was 1.84 (1.11–3.04;
P = 0.018, for trend). Both cases and
controls with the wild-type genotypes exhibited the most proficient
DRC. The risk (95% CI) for suboptimal DRC (defined as less than the
median DRC value among the controls) was 1.57 (0.74–3.35) for those
with the Gln/Gln751 genotype. For cases with the
Asn/Asn312 genotype, the risk (95% CI) was 3.50
(1.06–11.59). For cases who were homozygous at either locus, the risk
was 2.29 (1.03–5.12; P = 0.048, for
trend). The pattern was less evident among the controls, although there
was a nonsignificant 41% increase in the risk of suboptimal DRC for
controls who were homozygous at either locus. These results suggest
that the two XPD polymorphisms have a modulating effect
on DRC, especially in the cases.read more
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Journal ArticleDOI
Polymorphisms of DNA repair genes and risk of non-small cell lung cancer
Shanbeh Zienolddiny,Daniele Campa,Helge Lind,David Ryberg,Vidar Skaug,Lodve Stangeland,David H. Phillips,Federico Canzian,Aage Haugen +8 more
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References
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Benzo[alpha]pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes.
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Handbook of Human Genetic Linkage
Joseph D. Terwilliger,Jurg Ott +1 more
TL;DR: "Handbook of Human Genetic Linkage" contains detailed instructions on how to carry out linkage analysis, guiding the reader through each process on a step-by-step basis.
Journal Article
Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans.
Shen Mr,Jones Im,Mohrenweiser H +2 more
TL;DR: Estimation of the extent of DNA sequence variation among individuals in genes encoding proteins of the DNA repair pathways finds nine different amino acid substitution variants have been identified in resequencing of the exons of three nucleotide excision repair genes, a gene involved in double-strand break repair/recombination genes, and a gene functioning in base excision Repair and the repair of radiation-induced damage.
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