Genetic variation in the DNA repair genes is predictive of outcome in lung cancer.


Matakidou, A; el Galta, R; Webb, EL; Rudd, MF; Bridle, H; GELCAPS Consortium, ; Eisen, T; Houlston, RS; (2007) Genetic variation in the DNA repair genes is predictive of outcome in lung cancer. Human molecular genetics, 16 (19). pp. 2333-40. ISSN 0964-6906 DOI: https://doi.org/10.1093/hmg/ddm190

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Abstract

To assess whether DNA repair gene variants influence the clinical behaviour of lung cancer we examined the impact of a comprehensive panel of 109 non-synonymous single-nucleotide polymorphisms (nsSNPs) in 50 DNA repair genes on overall survival (OS) in 700 lung cancer patients. Fifteen nsSNPs were associated with OS, significantly greater than that expected (P = 0.04). SNPs associated with prognosis mapped primarily to two repair pathways--nucleotide excision repair (NER): ERCC5 D1104H (P = 0.004); ERCC6 G399D (P = 0.023), ERCC6 Q1413R (P = 0.025), POLE (P = 0.014) and base excision repair: APEX1 D148E (P = 0.028); EXO1 E670G (P = 0.007); POLB P242R (P = 0.018). An increasing number of variant alleles in EXO1 was associated with a poorer prognosis [hazard ratio (HR) = 1.24; P = 0.0009]. A role for variation in NER and BRCA2/FA pathway genes as determinants of OS was provided by an analysis restricted to the 456 patients treated with platinum-based agents. Our data indicate that the pathway-based approach has the potential to generate prognostic markers of clinical outcome.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 17855454
Web of Science ID: 250678000008
URI: http://researchonline.lshtm.ac.uk/id/eprint/2434

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