Evaluation of xeroderma pigmentosum XPA, XPC, XPD, XPF, XPB, XPG and DDB2 genes in familial early-onset lung cancer predisposition
✍ Scribed by Athena Matakidou; Tim Eisen; Christina Fleischmann; Helen Bridle; Richard S. Houlston; Members of the GELCAPS Consortium
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 73 KB
- Volume
- 119
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Epidemiological data has implicated heterozygosity for xeroderma pigmentosum (XP) as a risk factor for lung cancer. XP has 8 known complementation groups, 7 of which are caused by mutations in genes encoding components of the nucleotide excision repair (NER) pathway. To formally investigate the role of XP‐related NER genes in lung cancer susceptibility, we screened germline DNA from 92 familial early‐onset lung cancer patients for mutations in all coding regions and intron–exon boundaries of XPA, XPC, XPD, XPF, XPB, XPG and DDB2. Forty‐one exonic variants were identified. Twenty‐four were nonsynonymous, of which 14 were previously documented polymorphisms. Ten missense variants had not been previously described; none of which were detected in germline DNA from 278 cancer‐free controls. Two of the novel missense changes are predicted to be functionally deleterious. Our findings are compatible with XP heterozygosity being a risk factor for lung cancer susceptibility. © 2006 Wiley‐Liss, Inc.