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Int J Mol Epidemiol Genet 2011;2(2):145-155
Original Article
Discovery of common SNPs in the miR-205/200 family-regulated epithelial to
mesenchymal transition pathway and their association with risk for non-small
cell lung cancer
Shuguang Leng, Amanda M. Bernauer, Rihong Zhai, Carmen S. Tellez, Li Su, Elizabeth A. Burki, Maria A. Picchi, Christine A.
Stidley, Richard E. Crowell, David C. Christiani, Steven A. Belinsky
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico; Environmental and Occupational
Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston,
Massachusetts; Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico; New Mexico VA Health
Care System, Albuquerque, New Mexico; Department of Internal Medicine at University of New Mexico, Albuquerque, New
Mexico; and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Received February 24, 2011; accepted March 23, 2011; Epub April 1, 2011; published May 15, 2011
Abstract: The activation of the epithelial-to-mesenchymal transition (EMT) program is an important step for tumor initiation,
invasion, and metastasis in solid tumors, including lung cancer. The purpose of this study was to identify the sequence
variants in the miR-205/200 family-regulated EMT pathway and test their association with risk for lung cancer. Fifty samples
were resequenced to identify sequence variants in the miR-205/200 family-regulated EMT pathway. The association between
tagSNPs and risk for non-small cell lung cancer was discovered and validated in New Mexico (386 cases and 514 controls)
and Massachusetts (2453 cases and 1555 controls) case-control studies, respectively. The function of SNPs on miR-200b-a-
429 promoter activity was tested using luciferase reporter and expression assays. Forty-one sequence variants with minor
allele frequency ≥ 0.03 were identified, and 16 variants were selected as tagSNPs. Genetic association analysis identified that
the G allele of rs61768479 was associated with a 50% reduced risk for lung cancer (OR=0.50, 95%CI=0.300.85, uncorr-P=0.
01); however, this association was not validated (OR=0.90, 95%CI=0.721.13, uncorr-P=0.35). The G allele of rs61768479
was associated with lower promoter activity and miR expression by disrupting the binding of NKX2.5. In summary, no
association was identified between sequence variants in the miR-205/200 family-regulated EMT pathway and risk for lung
cancer. However, this study identified a comprehensive panel of tagSNPs (n=16) in the miR-205/200 family-regulated EMT
pathway that can be applied to other EMT-related phenotypes such as cancer chemoresistence and prognosis.
(IJMEG1102001).
Keywords: miR-200 family, miR-205, sequence variant, risk, lung cancer
Full Text PDF
Address all correspondence to:
Steven A. Belinsky, PhD
Lung Cancer Program
Lovelace Respiratory Research Institute
Albuquerque, New Mexico 87108
Phone: 505-348-9465; Fax: 505-348-4990
E-mail: sbelinsk@lrri.org
Original Article
Discovery of common SNPs in the miR-205/200 family-regulated epithelial to
mesenchymal transition pathway and their association with risk for non-small
cell lung cancer
Shuguang Leng, Amanda M. Bernauer, Rihong Zhai, Carmen S. Tellez, Li Su, Elizabeth A. Burki, Maria A. Picchi, Christine A.
Stidley, Richard E. Crowell, David C. Christiani, Steven A. Belinsky
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico; Environmental and Occupational
Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston,
Massachusetts; Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico; New Mexico VA Health
Care System, Albuquerque, New Mexico; Department of Internal Medicine at University of New Mexico, Albuquerque, New
Mexico; and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Received February 24, 2011; accepted March 23, 2011; Epub April 1, 2011; published May 15, 2011
Abstract: The activation of the epithelial-to-mesenchymal transition (EMT) program is an important step for tumor initiation,
invasion, and metastasis in solid tumors, including lung cancer. The purpose of this study was to identify the sequence
variants in the miR-205/200 family-regulated EMT pathway and test their association with risk for lung cancer. Fifty samples
were resequenced to identify sequence variants in the miR-205/200 family-regulated EMT pathway. The association between
tagSNPs and risk for non-small cell lung cancer was discovered and validated in New Mexico (386 cases and 514 controls)
and Massachusetts (2453 cases and 1555 controls) case-control studies, respectively. The function of SNPs on miR-200b-a-
429 promoter activity was tested using luciferase reporter and expression assays. Forty-one sequence variants with minor
allele frequency ≥ 0.03 were identified, and 16 variants were selected as tagSNPs. Genetic association analysis identified that
the G allele of rs61768479 was associated with a 50% reduced risk for lung cancer (OR=0.50, 95%CI=0.300.85, uncorr-P=0.
01); however, this association was not validated (OR=0.90, 95%CI=0.721.13, uncorr-P=0.35). The G allele of rs61768479
was associated with lower promoter activity and miR expression by disrupting the binding of NKX2.5. In summary, no
association was identified between sequence variants in the miR-205/200 family-regulated EMT pathway and risk for lung
cancer. However, this study identified a comprehensive panel of tagSNPs (n=16) in the miR-205/200 family-regulated EMT
pathway that can be applied to other EMT-related phenotypes such as cancer chemoresistence and prognosis.
(IJMEG1102001).
Keywords: miR-200 family, miR-205, sequence variant, risk, lung cancer
Full Text PDF
Address all correspondence to:
Steven A. Belinsky, PhD
Lung Cancer Program
Lovelace Respiratory Research Institute
Albuquerque, New Mexico 87108
Phone: 505-348-9465; Fax: 505-348-4990
E-mail: sbelinsk@lrri.org
