Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival

M. Rotunno, Y. Zhao, A. W. Bergen, J. Koshiol, L. Burdette, M. Rubagotti, R. I. Linnoila, F. M. Marincola, P. A. Bertazzi, A. C. Pesatori, N. E. Caporaso, L. M. McShane, E. Wang, M. T. Landi

Research output: Contribution to journalArticlepeer-review


Background: MicroRNAs (miRs) have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in genes involved in miR biogenesis may affect miR expression in lung tissue and be associated with lung carcinogenesis and progression. Methods: We analysed 12 SNPs in POLR2A, RNASEN and DICER1 genes in 1984 cases and 2073 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We investigated miR expression profiles in 165 lung adenocarcinoma (AD) and 125 squamous cell carcinoma tissue samples from the same population. We used logistic and Cox regression models to examine the association of individual genotypes and haplotypes with lung cancer risk and with lung cancer-specific survival, respectively. SNPs-miR expression associations in cases were assessed using two-sample t-tests and global permutation tests.Results:A haplotype in RNASEN (Drosha) was significantly associated with shorter lung cancer survival (hazard ratio1.86, 95% CI1.19-2.92, P0.007). In AD cases, a SNP within the same haplotype was associated with reduced RNASEN mRNA expression (P0.013) and with miR expression changes (global P0.007) of miRs known to be associated with cancer (e.g., let-7 family, miR-21, miR-25, miR-126 and miR15a). Conclusion: Inherited variation in the miR-processing machinery can affect miR expression levels and lung cancer-specific survival.

Original languageEnglish
Pages (from-to)1870-1874
Number of pages5
JournalBritish Journal of Cancer
Issue number12
Publication statusPublished - Dec 7 2010


  • lung cancer
  • microRNA biogenesis
  • polymorphism
  • survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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