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A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk

Open access
Chin, Lena J., Ratner, Elena, Leng, Shuguang, Zhai, Rihong, Nallur, Sunitha, Babar, Imran, Muller, Roman-Ulrich, Straka, Eva, Su, Li, Burki, Elizabeth A., Crowell, Richard E., Patel, Rajeshvari, Kulkarni, Trupti, Homer, Robert, Zelterman, Daniel, Kidd, Kenneth K., Zhu, Yong, Christiani, David C., Belinsky, Steven A., Slack, Frank J., Weidhaas, Joanne B.·2008·Cancer Research

Abstract

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 (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3′ untranslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) 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 (LCS) were sequenced in the KRAS 3′ untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 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 (confidence interval, 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 overexpression in vitro. The LCS6 variant allele in a KRAS miRANA 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. [Cancer Res 2008;68(20):8535–40]

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Metadata

Authors
Chin, L. J., Ratner, E., Leng, S., Zhai, R., Nallur, S., Babar, I., Muller, R.-U., Straka, E., Su, L., Burki, E. A., Crowell, R. E., Patel, R., Kulkarni, T., Homer, R., Zelterman, D., Kidd, K. K., Zhu, Y., Christiani, D. C., Belinsky, S. A., Slack, F. J., & Weidhaas, J. B.
Venue
Cancer Research
Published
2008-10-15
Volume
68
Issue
20
Pages
8535-8540
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2162425895
Cited by
632
References
35
FWCI
14.35
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk. https://app.cochat.ai/papers/10.1158/0008-5472.can-08-2129
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Chin, L. J., Ratner, E., Leng, S., Zhai, R., Nallur, S., Babar, I., Muller, R.-U., Straka, E., Su, L., Burki, E. A., Crowell, R. E., Patel, R., Kulkarni, T., Homer, R., Zelterman, D., Kidd, K. K., Zhu, Y., Christiani, D. C., Belinsky, S. A., . . . Weidhaas, J. B. (2008). A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-2129

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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