title: Common polymorphisms in D12S1034 flanking genes RASSF8 and BHLHB3 are not associated with lung adenocarcinoma risk.
abstract: The reported association between D12S1034 and lung adenocarcinoma (ADCA) risk [Yanagitani N, Kohno T, Sunaga N, et al. Localization of a human lung adenocarcinoma susceptibility locus, possibly syntenic to the mouse Pas1 locus, in the vicinity of the D12S1034 locus on chromosome 12p11.2-p12.1. Carcinogenesis. 2002;23:1177-83] prompted us to carry out a case-control study in lung ADCA and healthy control subjects to test possible involvement of single-nucleotide polymorphisms (SNPs) in D12S1034 flanking genes RASSF8 and BHLHB3, whose minimal distances from D12S1034 are approximately 16-24 kb. RASSF8 contains a RAS-associated domain and is a candidate tumor suppressor, whereas BHLHB3 is a basic helix-loop-helix domain-containing protein that functions as a transcriptional repressor. We observed no significant association between common SNPs in RASSF8 (rs1546550 in the 3'-UTR and 3 intronic SNPs) and BHLHB3 (Ala298Val and rs1048155 in the 3'-UTR) with lung ADCA risk. However, patient groups carrying one or two copies of the BHLHB3 Val298 variation (i.e., Ala/Val or Val/Val genotypes) had a higher proportion of short-term survivors (hazard ratio, 1.8; 95% confidence interval, 1.2-2.7) compared with those carrying the Ala/Ala genotype. A replication study in an independent Norwegian lung cancer population of multiple cancer histotypes failed to replicate the significant association of BHLHB3 Ala298Val with survival; such association, however, was confirmed by analysis of ADCA only from both populations. Our results suggest that BHLHB3 variants may affect lung ADCA prognosis.
authors.affiliation: Department of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy.
authors.forename: F Stefania
authors.initials: FS
authors.lastname: Falvella
authors.forename: Monica
authors.initials: M
authors.lastname: Spinola
authors.forename: Giacomo
authors.initials: G
authors.lastname: Manenti
authors.forename: Barbara
authors.initials: B
authors.lastname: Conti
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Vidar
authors.initials: V
authors.lastname: Skaug
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis