A SNP in a let-7 microRNA complementary site in the KRAS 3′UTR Increases Non-Small Cell Lung Cancer Risk

By Lena J. Chin, E. Ratner, S. Leng, R. Zhai, Sunitha Nallur, I. Babar, Roman-Ulrich Muller, Eva Straka, L. Su, Elizabeth A. Burki and 11 more. Cancer Research, 2008

658 citations recorded by the source corpus.

Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNAs) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3′UTRs (untranslated regions) of their target messenger RNAs (mRNAs). The purpose of this study was to identify single nucleotide polymorphisms (SNPs) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCSs) were sequenced in the KRAS 3′UTR from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously un-identified SNP at LCS6 was characterized in 2433 people (representing 46 human populations). The frequency of the variant allele is 18.1–20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (C.I.= 1.1–4.6, p = 0.02) for NSCLC cancer in patients who smoked < 40 pack years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS over-expression in vitro. The LCS6 variant allele in a KRAS miRNA complementary site is significantly associated with increased risk for NSCLC among moderate smokers, and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9ce8a1b509893f6406d5b3024115e42edbdbb87b

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

MicroRNA: Biogenesis, Function and Role in Cancer (2010, background): “MiRNA signature profiles can be used to determine prognosis [338340], response to drug therapy [341], predict treatment efficiency [342, 343], race susceptibility [23] and patient susceptibility to cancer and metastasis [344-346].”
MicroRNAs in stress signaling and human disease (2012, background): “This variant was first identified by sequencing the KRAS 30 UTR in non-small-cell lung cancer (NSCLC) samples and found to be enriched in patients in two independent NSCLC case-control cohorts (Chin et al., 2008).”
The mammalian ovary from genesis to revelation. (2009, background): “Potential mechanisms of miRNA deregulation in cancer are diverse and include defects in miRNA processing (638), DNA copy number abnormalities (639–641), epigenetic alterations (641, 642), mutations in the miRNA or its mRNA binding site (643), and aberrant transcription (644).”
MicroRNA (miRNA) in cancer (2015, background): “Additionally, SNPs in target sites of miRNAs may also result in the escape of degradation by miRNA [41].”
Evolution of microRNA diversity and regulation in animals (2011, background): “Indeed, there is growing evidence for roles of SNPs in miRNA target sites in cance”
Causes and consequences of microRNA dysregulation in cancer (2009, background): “Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation.”
MicroRNAs in body fluids—the mix of hormones and biomarkers (2011, positive): “For example, a SNP found in the binding site of let-7 in the 3′-UTR of the KRAS gene increased the risk of lung cancer in moderate smokers”