Journal Article

Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer

Antonella Galvan, Felicia S. Falvella, Elisa Frullanti, Monica Spinola, Matteo Incarbone, Mario Nosotti, Luigi Santambrogio, Barbara Conti, Ugo Pastorino, Anna Gonzalez-Neira and Tommaso A. Dragani

in Carcinogenesis

Volume 31, issue 3, pages 462-465
Published in print March 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp315
Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer

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We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case–control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

Journal Article.  2677 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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