The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including UGT2B17 is an important mechanism for 4-(me...
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| Veröffentlicht in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2007-04, Vol.16 (4), p.823-828 |
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| creator | GALLAGHER, Carla J MUSCAT, Joshua E HICKS, Amy N YAN ZHENG DYER, Anne-Marie CHASE, Gary A RICHIE, John LAZARUS, Philip |
| description | 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation
of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including
UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in ∼10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro . In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects
on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide
to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes ( P = 0.058). There were no significant differences in this ratio by genotype in men ( P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence
interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3).
The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung
histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation
rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer
Epidemiol Biomarkers Prev 2007;16(4):823–8) |
| doi_str_mv | 10.1158/1055-9965.EPI-06-0823 |
| format | Article |
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of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including
UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in ∼10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro . In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects
on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide
to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes ( P = 0.058). There were no significant differences in this ratio by genotype in men ( P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence
interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3).
The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung
histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation
rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer
Epidemiol Biomarkers Prev 2007;16(4):823–8)</description><identifier>ISSN: 1055-9965</identifier><identifier>EISSN: 1538-7755</identifier><identifier>DOI: 10.1158/1055-9965.EPI-06-0823</identifier><identifier>PMID: 17416778</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adenocarcinoma - enzymology ; Adenocarcinoma - epidemiology ; Adenocarcinoma - genetics ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Florida - epidemiology ; Gene Deletion ; Genotype ; Genotype-phenotype correlations ; Glucuronosyltransferase - genetics ; Humans ; Logistic Models ; Lung cancer ; Lung Neoplasms - enzymology ; Lung Neoplasms - epidemiology ; Lung Neoplasms - genetics ; Male ; Medical sciences ; New York - epidemiology ; Nitrosamines - urine ; Phenotype ; Pneumology ; Polymorphisms in carcinogen metabolism and cancer risk ; Pyridines - urine ; Risk ; Smoking - epidemiology ; Tobacco ; Tumors ; Tumors of the respiratory system and mediastinum</subject><ispartof>Cancer epidemiology, biomarkers & prevention, 2007-04, Vol.16 (4), p.823-828</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c315t-a9b06a3b88ddee9b5daa267ee3f7d49ecefee5cef64ce97c76a245ab39b5149b3</citedby><cites>FETCH-LOGICAL-c315t-a9b06a3b88ddee9b5daa267ee3f7d49ecefee5cef64ce97c76a245ab39b5149b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3347,27915,27916</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18776959$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17416778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GALLAGHER, Carla J</creatorcontrib><creatorcontrib>MUSCAT, Joshua E</creatorcontrib><creatorcontrib>HICKS, Amy N</creatorcontrib><creatorcontrib>YAN ZHENG</creatorcontrib><creatorcontrib>DYER, Anne-Marie</creatorcontrib><creatorcontrib>CHASE, Gary A</creatorcontrib><creatorcontrib>RICHIE, John</creatorcontrib><creatorcontrib>LAZARUS, Philip</creatorcontrib><title>The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer</title><title>Cancer epidemiology, biomarkers & prevention</title><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><description>4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation
of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including
UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in ∼10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro . In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects
on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide
to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes ( P = 0.058). There were no significant differences in this ratio by genotype in men ( P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence
interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3).
The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung
histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation
rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer
Epidemiol Biomarkers Prev 2007;16(4):823–8)</description><subject>Adenocarcinoma - enzymology</subject><subject>Adenocarcinoma - epidemiology</subject><subject>Adenocarcinoma - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Case-Control Studies</subject><subject>Cross-Sectional Studies</subject><subject>Female</subject><subject>Florida - epidemiology</subject><subject>Gene Deletion</subject><subject>Genotype</subject><subject>Genotype-phenotype correlations</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Humans</subject><subject>Logistic Models</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - enzymology</subject><subject>Lung Neoplasms - epidemiology</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>New York - epidemiology</subject><subject>Nitrosamines - urine</subject><subject>Phenotype</subject><subject>Pneumology</subject><subject>Polymorphisms in carcinogen metabolism and cancer risk</subject><subject>Pyridines - urine</subject><subject>Risk</subject><subject>Smoking - epidemiology</subject><subject>Tobacco</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>1055-9965</issn><issn>1538-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhiMEoqXwCCBvgLJwsZPYTrprp2WoNIgR7awtxzlpDIk92InaPGFfC6czVZdsfJG-c9H_Jcl7Sk4oZcVXShjDZcnZyeX6ChOOSZFmL5JDyrICC8HYy_h-Yg6SNyH8JoSIkrHXyQEVOeVCFIfJw00LaHOxxstu1KN31oWpG7yyoQGvAqD0nAq0BAvoAjoYjLNo7bqpd37bmtCfomu4x9db0KYxGp2F4LRRj9idGVq08cYqP6EcH_-AoZ06awbvguqNdV8wxccZXk_e1FM3_87HQVnXoadlTL1rtW7BumHaAlK2Rr9M-IMa59FqtLdooawG_zZ51aguwLv9fZRsvl3eLL7j1c_l1eJshXVG2YBVWRGusqoo6hqgrFitVMoFQNaIOi9BQwPA4slzDaXQgqs0Z6rKIkrzssqOkk-7vlvv_o4QBtmboKHrlAU3BilIxqOJ9L9gSkTKi2IG2Q7UMZfgoZFbb_qYmaREzqrlrFHOGmVULQmXs-pY92E_YKx6qJ-r9m4j8HEPqKBV10Sp2oRnrhCCl6yM3Ocd15rb9s54kPoxUg8BlNetpFzmch75DxICw9Y</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>GALLAGHER, Carla J</creator><creator>MUSCAT, Joshua E</creator><creator>HICKS, Amy N</creator><creator>YAN ZHENG</creator><creator>DYER, Anne-Marie</creator><creator>CHASE, Gary A</creator><creator>RICHIE, John</creator><creator>LAZARUS, Philip</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><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>7U1</scope><scope>7U2</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200704</creationdate><title>The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer</title><author>GALLAGHER, Carla J ; MUSCAT, Joshua E ; HICKS, Amy N ; YAN ZHENG ; DYER, Anne-Marie ; CHASE, Gary A ; RICHIE, John ; LAZARUS, Philip</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-a9b06a3b88ddee9b5daa267ee3f7d49ecefee5cef64ce97c76a245ab39b5149b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - enzymology</topic><topic>Adenocarcinoma - epidemiology</topic><topic>Adenocarcinoma - genetics</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Case-Control Studies</topic><topic>Cross-Sectional Studies</topic><topic>Female</topic><topic>Florida - epidemiology</topic><topic>Gene Deletion</topic><topic>Genotype</topic><topic>Genotype-phenotype correlations</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Humans</topic><topic>Logistic Models</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - enzymology</topic><topic>Lung Neoplasms - epidemiology</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>New York - epidemiology</topic><topic>Nitrosamines - urine</topic><topic>Phenotype</topic><topic>Pneumology</topic><topic>Polymorphisms in carcinogen metabolism and cancer risk</topic><topic>Pyridines - urine</topic><topic>Risk</topic><topic>Smoking - epidemiology</topic><topic>Tobacco</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GALLAGHER, Carla J</creatorcontrib><creatorcontrib>MUSCAT, Joshua E</creatorcontrib><creatorcontrib>HICKS, Amy N</creatorcontrib><creatorcontrib>YAN ZHENG</creatorcontrib><creatorcontrib>DYER, Anne-Marie</creatorcontrib><creatorcontrib>CHASE, Gary A</creatorcontrib><creatorcontrib>RICHIE, John</creatorcontrib><creatorcontrib>LAZARUS, Philip</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GALLAGHER, Carla J</au><au>MUSCAT, Joshua E</au><au>HICKS, Amy N</au><au>YAN ZHENG</au><au>DYER, Anne-Marie</au><au>CHASE, Gary A</au><au>RICHIE, John</au><au>LAZARUS, Philip</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer</atitle><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><date>2007-04</date><risdate>2007</risdate><volume>16</volume><issue>4</issue><spage>823</spage><epage>828</epage><pages>823-828</pages><issn>1055-9965</issn><eissn>1538-7755</eissn><abstract>4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation
of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including
UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in ∼10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro . In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects
on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide
to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes ( P = 0.058). There were no significant differences in this ratio by genotype in men ( P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence
interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3).
The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung
histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation
rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer
Epidemiol Biomarkers Prev 2007;16(4):823–8)</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>17416778</pmid><doi>10.1158/1055-9965.EPI-06-0823</doi><tpages>6</tpages></addata></record> |
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| ispartof | Cancer epidemiology, biomarkers & prevention, 2007-04, Vol.16 (4), p.823-828 |
| issn | 1055-9965 1538-7755 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Adenocarcinoma - enzymology Adenocarcinoma - epidemiology Adenocarcinoma - genetics Biological and medical sciences Biomarkers, Tumor - genetics Case-Control Studies Cross-Sectional Studies Female Florida - epidemiology Gene Deletion Genotype Genotype-phenotype correlations Glucuronosyltransferase - genetics Humans Logistic Models Lung cancer Lung Neoplasms - enzymology Lung Neoplasms - epidemiology Lung Neoplasms - genetics Male Medical sciences New York - epidemiology Nitrosamines - urine Phenotype Pneumology Polymorphisms in carcinogen metabolism and cancer risk Pyridines - urine Risk Smoking - epidemiology Tobacco Tumors Tumors of the respiratory system and mediastinum |
| title | The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer |
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