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 journalArticle

29 Citations (Scopus)

Abstract

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
Volume103
Issue number12
DOIs
Publication statusPublished - 7 Dec 2010
Externally publishedYes

Fingerprint

RNA Interference
MicroRNAs
Lung Neoplasms
Single Nucleotide Polymorphism
Haplotypes
Lung
Carcinogenesis
Proportional Hazards Models
Genes
Squamous Cell Carcinoma
Adenocarcinoma
Logistic Models
Genotype
Messenger RNA
Population
Neoplasms

Keywords

  • lung cancer
  • microRNA biogenesis
  • polymorphism
  • survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rotunno, M., Zhao, Y., Bergen, A. W., Koshiol, J., Burdette, L., Rubagotti, M., ... Landi, M. T. (2010). Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival. British Journal of Cancer, 103(12), 1870-1874. https://doi.org/10.1038/sj.bjc.6605976

Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival. / Rotunno, M.; Zhao, Y.; Bergen, A. W.; Koshiol, J.; Burdette, L.; Rubagotti, M.; Linnoila, R. I.; Marincola, F. M.; Bertazzi, P. A.; Pesatori, A. C.; Caporaso, N. E.; McShane, L. M.; Wang, E.; Landi, M. T.

In: British Journal of Cancer, Vol. 103, No. 12, 07.12.2010, p. 1870-1874.

Research output: Contribution to journalArticle

Rotunno, M, Zhao, Y, Bergen, AW, Koshiol, J, Burdette, L, Rubagotti, M, Linnoila, RI, Marincola, FM, Bertazzi, PA, Pesatori, AC, Caporaso, NE, McShane, LM, Wang, E & Landi, MT 2010, 'Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival', British Journal of Cancer, vol. 103, no. 12, pp. 1870-1874. https://doi.org/10.1038/sj.bjc.6605976
Rotunno, M. ; Zhao, Y. ; Bergen, A. W. ; Koshiol, J. ; Burdette, L. ; Rubagotti, M. ; Linnoila, R. I. ; Marincola, F. M. ; Bertazzi, P. A. ; Pesatori, A. C. ; Caporaso, N. E. ; McShane, L. M. ; Wang, E. ; Landi, M. T. / Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival. In: British Journal of Cancer. 2010 ; Vol. 103, No. 12. pp. 1870-1874.
@article{dcdd822f375b4afe80bf130df6188c17,
title = "Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival",
abstract = "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.",
keywords = "lung cancer, microRNA biogenesis, polymorphism, survival",
author = "M. Rotunno and Y. Zhao and Bergen, {A. W.} and J. Koshiol and L. Burdette and M. Rubagotti and Linnoila, {R. I.} and Marincola, {F. M.} and Bertazzi, {P. A.} and Pesatori, {A. C.} and Caporaso, {N. E.} and McShane, {L. M.} and E. Wang and Landi, {M. T.}",
year = "2010",
month = "12",
day = "7",
doi = "10.1038/sj.bjc.6605976",
language = "English",
volume = "103",
pages = "1870--1874",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Inherited polymorphisms in the RNA-mediated interference machinery affect microRNA expression and lung cancer survival

AU - Rotunno, M.

AU - Zhao, Y.

AU - Bergen, A. W.

AU - Koshiol, J.

AU - Burdette, L.

AU - Rubagotti, M.

AU - Linnoila, R. I.

AU - Marincola, F. M.

AU - Bertazzi, P. A.

AU - Pesatori, A. C.

AU - Caporaso, N. E.

AU - McShane, L. M.

AU - Wang, E.

AU - Landi, M. T.

PY - 2010/12/7

Y1 - 2010/12/7

N2 - 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.

AB - 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.

KW - lung cancer

KW - microRNA biogenesis

KW - polymorphism

KW - survival

UR - http://www.scopus.com/inward/record.url?scp=78649985195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649985195&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6605976

DO - 10.1038/sj.bjc.6605976

M3 - Article

C2 - 21102586

AN - SCOPUS:78649985195

VL - 103

SP - 1870

EP - 1874

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 12

ER -