Journal Article

The <i>XPD</i> variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk

Sai-Mei Hou, Susann Fält, Sabrina Angelini, Ke Yang, Fredrik Nyberg, Bo Lambert and Kari Hemminki

in Carcinogenesis

Volume 23, issue 4, pages 599-603
Published in print April 2002 | ISSN: 0143-3334
Published online April 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.4.599
The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The DNA repair protein xeroderma pigmentosum complementation group D (XPD) is involved in the nucleotide excision repair of DNA lesions induced by many tobacco and environmental carcinogens. In order to study the functional impact of the common polymorphisms in XPD exon 10 (G > A, Asp312Asn) and exon 23 (A > C, Lys751Gln), we have genotyped 185 Swedish lung cancer cases (97 smokers and 88 never-smokers) and 162 matched population controls (83 smokers and 79 never-smokers). Presence of one or two variant alleles was associated with increased risk for lung cancer among never-smokers only, in particular younger (<70 years) never-smokers [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.1–6.5 for exon 10; OR = 3.2, 95% CI = 1.3–8.0 for exon 23, adjusted for age, gender and environmental tobacco smoke]. Aromatic DNA adduct level (AL) in peripheral lymphocytes was found to be similar between cases and controls, but significantly increased by current or recent smoking. Overall, there was a significant trend for increasing AL with increasing number of variant alleles in exon 10 (P = 0.02) or in exon 23 (P = 0.001). In addition, subjects with the combined exon 10 AA and exon 23 CC genotype showed a significantly higher AL compared with all those with any of the other genotypes (P = 0.02). We conclude that the XPD variant alleles may be associated with reduced repair of aromatic DNA adducts in general and increased lung cancer risk among never-smokers.

Keywords: AL, adduct level; CI, confidence interval; ETS, environmental tobacco smoke; NER, nucleotide excision repair; OR, odds ratio; PAH, polycyclic aromatic hydrocarbons; XPD, xeroderma pigmentosum complementation group D.

Journal Article.  4176 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.