KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer.
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.
Nelson
H H
HH
Masonic Cancer Center, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA. hhnelson@umn.edu
Christensen
B C
BC
Plaza
S L
SL
Wiencke
J K
JK
Marsit
C J
CJ
Kelsey
K T
KT
D020413:3' Untranslated Regions / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D056726:Genetic Association Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C487931:mirnlet7 microRNA, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins