The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
A SNP in a let-7 microRNA Complementary Site in the KRAS 3′ Untranslated Region Increases Non–Small Cell Lung Cancer Risk
Open accessAbstract
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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- 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).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.