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

Ana B. Galván | Zendy; Felicia Stefania Falvella | Zendy; Elisa Frullanti | Zendy; M Spinola | Zendy; Marco Incarbone | Zendy; Mario Nosotti | Zendy; L. Santambrogio | Zendy; Bárbara Conti | Zendy; Ugo Pastorino | Zendy; Anna GonzálezNeira | Zendy; Tommaso A. Dragani | Zendy

Open Access

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

Author(s) -

Ana B. Galván,

Felicia Stefania Falvella,

Elisa Frullanti,

M Spinola,

Marco Incarbone,

Mario Nosotti,

L. Santambrogio,

Bárbara Conti,

Ugo Pastorino,

Anna GonzálezNeira,

Tommaso A. Dragani

Publication year - 2009

Publication title -

carcinogenesis

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.688

H-Index - 204

eISSN - 1460-2180

pISSN - 0143-3334

DOI - 10.1093/carcin/bgp315

Subject(s) - single nucleotide polymorphism , biology , genome wide association study , lung cancer , genetics , snp , genetic association , genotyping , allele , linkage disequilibrium , snp genotyping , lung cancer susceptibility , population , tag snp , genotype , oncology , medicine , gene , environmental health

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.

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