KRAS mutation, KRAS–LCS6 polymorphism, and non-small cell lung cancer

Nelson, H.H.; Christensen, B.C.; Plaza, S.L.; Wiencke, J.K.; Marsit, C.J.; Kelsey, K.T.

doi:10.1016/j.lungcan.2009.09.008

« Previous Next »Lung Cancer
Volume 69, Issue 1 , Pages 51-53, July 2010

KRAS mutation, KRAS–LCS6 polymorphism, and non-small cell lung cancer

H.H. Nelson
- Masonic Cancer Center, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, United States
- Corresponding author.
B.C. Christensen
- Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, United States
- Department of Community Health, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, United States
S.L. Plaza
- Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, United States
J.K. Wiencke
- Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143, United States
C.J. Marsit
- Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, United States
K.T. Kelsey
- Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, United States
- Department of Community Health, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, United States

Received 27 April 2009; received in revised form 25 August 2009; accepted 19 September 2009. published online 26 October 2009.

Abstract

The let-7 family of microRNAs are important regulatory molecules in lung cancer. One downstream target of let-7 is the RAS gene family, including KRAS, an important oncogene in the etiology and clinical outcome of lung adenocarcinoma. Recently, a SNP in the let-7 binding region of the KRAS 3′ UTR was identified (termed LCS6). This functional polymorphism alters let-7 binding, resulting in both increased KRAS expression and decreased let-7 exposure. Further, this SNP has been reported as a risk trait for lung cancer among low-moderate smokers. Given the functionality of LCS6, we tested the hypothesis that this SNP is associated with the occurrence of KRAS mutation as well as patient survival. Here, we report there is no association between the LCS6 KRAS polymorphism and KRAS mutation. Further, we find no association between the LCS6 polymorphism and lung cancer survival. These unexpected findings imply that this newly reported KRAS–LCS6 polymorphism will have limited clinical utility for NSCLC.