Common polymorphisms in D12S1034 flanking genes RASSF8 and BHLHB3 are not associated with lung adenocarcinoma risk

F. Stefania Falvella, Monica Spinola, Giacomo Manenti, Barbara Conti, Ugo Pastorino, Vidar Skaug, Aage Haugen, Tommaso A. Dragani

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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 ∼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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalLung Cancer
Issue number1
Publication statusPublished - Apr 2007


  • DEC2
  • Genetic predisposition
  • KRAS
  • Lung cancer
  • SHARP-1

ASJC Scopus subject areas

  • Oncology


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