A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk
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 reg...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2008-10, Vol.68 (20), p.8535-8540 |
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| creator | 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 |
| description | 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 |
| doi_str_mv | 10.1158/0008-5472.CAN-08-2129 |
| format | Article |
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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.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-08-2129</identifier><identifier>PMID: 18922928</identifier><language>eng</language><publisher>United States</publisher><subject>3' Untranslated Regions - chemistry ; Alleles ; Carcinoma, Non-Small-Cell Lung - etiology ; Carcinoma, Non-Small-Cell Lung - genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms - etiology ; Lung Neoplasms - genetics ; Male ; MicroRNAs - genetics ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins - genetics ; Risk ; Smoking - adverse effects</subject><ispartof>Cancer research (Chicago, Ill.), 2008-10, Vol.68 (20), p.8535-8540</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-e9d111706d372299ea2930cf57bf5ada71eabe78980c1bb6f7e3e800df84bdc53</citedby><cites>FETCH-LOGICAL-c506t-e9d111706d372299ea2930cf57bf5ada71eabe78980c1bb6f7e3e800df84bdc53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3343,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18922928$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chin, Lena J</creatorcontrib><creatorcontrib>Ratner, Elena</creatorcontrib><creatorcontrib>Leng, Shuguang</creatorcontrib><creatorcontrib>Zhai, Rihong</creatorcontrib><creatorcontrib>Nallur, Sunitha</creatorcontrib><creatorcontrib>Babar, Imran</creatorcontrib><creatorcontrib>Muller, Roman-Ulrich</creatorcontrib><creatorcontrib>Straka, Eva</creatorcontrib><creatorcontrib>Su, Li</creatorcontrib><creatorcontrib>Burki, Elizabeth A</creatorcontrib><creatorcontrib>Crowell, Richard E</creatorcontrib><creatorcontrib>Patel, Rajeshvari</creatorcontrib><creatorcontrib>Kulkarni, Trupti</creatorcontrib><creatorcontrib>Homer, Robert</creatorcontrib><creatorcontrib>Zelterman, Daniel</creatorcontrib><creatorcontrib>Kidd, Kenneth K</creatorcontrib><creatorcontrib>Zhu, Yong</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Belinsky, Steven A</creatorcontrib><creatorcontrib>Slack, Frank J</creatorcontrib><creatorcontrib>Weidhaas, Joanne B</creatorcontrib><title>A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>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.</description><subject>3' Untranslated Regions - chemistry</subject><subject>Alleles</subject><subject>Carcinoma, Non-Small-Cell Lung - etiology</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Humans</subject><subject>Lung Neoplasms - etiology</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>MicroRNAs - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins p21(ras)</subject><subject>ras Proteins - genetics</subject><subject>Risk</subject><subject>Smoking - adverse effects</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkFtPwyAUgInRuDn9CRqe9KkKbSn0sVm8xWWaTZ8Jpaez2tIJ9GH_Xpot-nI4JN-5fQhdUnJLKRN3hBARsZTHt_NiGYU8pnF-hKaUJSLiacqO0fSPmaAz577Cl1HCTtGEijyO81hM0a7A6-UbbgxWuAUfcdw12varZYF1321b6MB4ZXfYNR5GzH8CflkVa5zc4MF4q4xrlYcKW9g0vQmItqAcOGx6E7lOtS3WEEI7mA3Wymiw2Dbu-xyd1Kp1cHF4Z-jj4f59_hQtXh-f58Ui0oxkPoK8opRyklUJDzvnoOI8IbpmvKyZqhSnoErgIhdE07LMag4JCEKqWqRlpVkyQ9f7vlvb_wzgvOwaN26kDPSDk1meZYynPIBsD4b7nbNQy61tunC7pESOzuXoU44-ZXAuQz46D3VXhwFD2UH1X3WQnPwC2D99Ew</recordid><startdate>20081015</startdate><enddate>20081015</enddate><creator>Chin, Lena J</creator><creator>Ratner, Elena</creator><creator>Leng, Shuguang</creator><creator>Zhai, Rihong</creator><creator>Nallur, Sunitha</creator><creator>Babar, Imran</creator><creator>Muller, Roman-Ulrich</creator><creator>Straka, Eva</creator><creator>Su, Li</creator><creator>Burki, Elizabeth A</creator><creator>Crowell, Richard E</creator><creator>Patel, Rajeshvari</creator><creator>Kulkarni, Trupti</creator><creator>Homer, Robert</creator><creator>Zelterman, Daniel</creator><creator>Kidd, Kenneth K</creator><creator>Zhu, Yong</creator><creator>Christiani, David C</creator><creator>Belinsky, Steven A</creator><creator>Slack, Frank J</creator><creator>Weidhaas, Joanne B</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20081015</creationdate><title>A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c506t-e9d111706d372299ea2930cf57bf5ada71eabe78980c1bb6f7e3e800df84bdc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>3' Untranslated Regions - chemistry</topic><topic>Alleles</topic><topic>Carcinoma, Non-Small-Cell Lung - etiology</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Humans</topic><topic>Lung Neoplasms - etiology</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>MicroRNAs - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins p21(ras)</topic><topic>ras Proteins - genetics</topic><topic>Risk</topic><topic>Smoking - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chin, Lena J</creatorcontrib><creatorcontrib>Ratner, Elena</creatorcontrib><creatorcontrib>Leng, Shuguang</creatorcontrib><creatorcontrib>Zhai, Rihong</creatorcontrib><creatorcontrib>Nallur, Sunitha</creatorcontrib><creatorcontrib>Babar, Imran</creatorcontrib><creatorcontrib>Muller, Roman-Ulrich</creatorcontrib><creatorcontrib>Straka, Eva</creatorcontrib><creatorcontrib>Su, Li</creatorcontrib><creatorcontrib>Burki, Elizabeth A</creatorcontrib><creatorcontrib>Crowell, Richard E</creatorcontrib><creatorcontrib>Patel, Rajeshvari</creatorcontrib><creatorcontrib>Kulkarni, Trupti</creatorcontrib><creatorcontrib>Homer, Robert</creatorcontrib><creatorcontrib>Zelterman, Daniel</creatorcontrib><creatorcontrib>Kidd, Kenneth K</creatorcontrib><creatorcontrib>Zhu, Yong</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Belinsky, Steven A</creatorcontrib><creatorcontrib>Slack, Frank J</creatorcontrib><creatorcontrib>Weidhaas, Joanne B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chin, Lena J</au><au>Ratner, Elena</au><au>Leng, Shuguang</au><au>Zhai, Rihong</au><au>Nallur, Sunitha</au><au>Babar, Imran</au><au>Muller, Roman-Ulrich</au><au>Straka, Eva</au><au>Su, Li</au><au>Burki, Elizabeth A</au><au>Crowell, Richard E</au><au>Patel, Rajeshvari</au><au>Kulkarni, Trupti</au><au>Homer, Robert</au><au>Zelterman, Daniel</au><au>Kidd, Kenneth K</au><au>Zhu, Yong</au><au>Christiani, David C</au><au>Belinsky, Steven A</au><au>Slack, Frank J</au><au>Weidhaas, Joanne B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2008-10-15</date><risdate>2008</risdate><volume>68</volume><issue>20</issue><spage>8535</spage><epage>8540</epage><pages>8535-8540</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><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.</abstract><cop>United States</cop><pmid>18922928</pmid><doi>10.1158/0008-5472.CAN-08-2129</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2008-10, Vol.68 (20), p.8535-8540 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | 3' Untranslated Regions - chemistry Alleles Carcinoma, Non-Small-Cell Lung - etiology Carcinoma, Non-Small-Cell Lung - genetics Case-Control Studies Female Genetic Predisposition to Disease Humans Lung Neoplasms - etiology Lung Neoplasms - genetics Male MicroRNAs - genetics Polymorphism, Single Nucleotide Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) ras Proteins - genetics Risk Smoking - adverse effects |
| title | A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk |
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