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, Tommaso A. Dragani

Research output: Contribution to journalArticle

Abstract

We analyzed a series of young (median age = 52 years) nonsmoker 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.

Original languageEnglish
Pages (from-to)462-465
Number of pages4
JournalCarcinogenesis
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2010

ASJC Scopus subject areas

  • Cancer Research

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