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Evaluation of xeroderma pigmentosum XPA , XPC , XPD , XPF , XPB , XPG and DDB2 genes in familial early‐onset lung cancer predisposition
Author(s) -
Matakidou Athena,
Eisen Tim,
Fleischmann Christina,
Bridle Helen,
Houlston Richard S.
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21931
Subject(s) - xeroderma pigmentosum , nucleotide excision repair , biology , genetics , missense mutation , loss of heterozygosity , cancer research , exon , dna repair , gene , mutation , allele
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.