International Lung Cancer Consortium : Coordinated association study of 10 potential lung cancer susceptibility variants

Background . Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation ( IL1B ), folate metabolism ( MTHFR ), regulatory function ( AKAP9 and CAMKK1 ), cell adhesion ( SEZL6 ) and apoptosis ( FAS , FASL , TP53 , TP53BP1 and BAT3 ). Methods. Genotype data from 15 ILCCO case–control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results . Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P  = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P  = 6 × 10 −4 ). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we...