Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women
Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens...
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| Veröffentlicht in: | European journal of clinical pharmacology 2003-09, Vol.59 (5-6), p.471-476 |
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| creator | PING HUANG BING ZHU WANG, Lian-Sheng OUYANG, Dong-Sheng HUANG, Song-Lin CHEN, Xiao-Ping ZHOU, Hong-Hao |
| description | Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens is related to their major oxidative metabolites, 16alpha-hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16alpha-hydroxylation of estrogens. Furthermore, CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue. Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility.
To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity.
One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography.
Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls ( P |
| doi_str_mv | 10.1007/s00228-003-0649-4 |
| format | Article |
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To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity.
One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography.
Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls ( P<0.001), and the CYP3A activity of patients with lymph-node metastasis was higher than that of patients without lymph-node metastasis ( P=0.028). CYP3A activity in estrogen receptor or progesterone receptor positive cases was the same as in estrogen receptor or progesterone receptor negative cases ( P=0.124, 0.175).
Our results indicate that high CYP3A activity may contribute to breast cancer disease genesis and may promote breast cancer to lymph-node metastasis.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-003-0649-4</identifier><identifier>PMID: 12937874</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Aryl Hydrocarbon Hydroxylases - genetics ; Aryl Hydrocarbon Hydroxylases - metabolism ; Asian Continental Ancestry Group ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - ethnology ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; China ; Cytochrome P-450 CYP3A ; Disease Susceptibility ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Lymphatic Metastasis ; Mammary gland diseases ; Medical sciences ; Midazolam - analogs & derivatives ; Midazolam - blood ; Midazolam - metabolism ; Oxidoreductases, N-Demethylating - genetics ; Oxidoreductases, N-Demethylating - metabolism ; Receptors, Estrogen - metabolism ; Receptors, Progesterone - metabolism ; Risk Factors ; Tumors</subject><ispartof>European journal of clinical pharmacology, 2003-09, Vol.59 (5-6), p.471-476</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Springer-Verlag 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-e0e81c063302012ac381bc28d9c020e8ca48bc8d61df01c7f636035beed43c023</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15155852$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12937874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PING HUANG</creatorcontrib><creatorcontrib>BING ZHU</creatorcontrib><creatorcontrib>WANG, Lian-Sheng</creatorcontrib><creatorcontrib>OUYANG, Dong-Sheng</creatorcontrib><creatorcontrib>HUANG, Song-Lin</creatorcontrib><creatorcontrib>CHEN, Xiao-Ping</creatorcontrib><creatorcontrib>ZHOU, Hong-Hao</creatorcontrib><title>Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><description>Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens is related to their major oxidative metabolites, 16alpha-hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16alpha-hydroxylation of estrogens. Furthermore, CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue. Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility.
To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity.
One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography.
Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls ( P<0.001), and the CYP3A activity of patients with lymph-node metastasis was higher than that of patients without lymph-node metastasis ( P=0.028). CYP3A activity in estrogen receptor or progesterone receptor positive cases was the same as in estrogen receptor or progesterone receptor negative cases ( P=0.124, 0.175).
Our results indicate that high CYP3A activity may contribute to breast cancer disease genesis and may promote breast cancer to lymph-node metastasis.</description><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>Asian Continental Ancestry Group</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - ethnology</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>China</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Disease Susceptibility</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Midazolam - analogs & derivatives</subject><subject>Midazolam - blood</subject><subject>Midazolam - metabolism</subject><subject>Oxidoreductases, N-Demethylating - genetics</subject><subject>Oxidoreductases, N-Demethylating - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, Progesterone - metabolism</subject><subject>Risk Factors</subject><subject>Tumors</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpFkE1LAzEQhoMotn78AC8SBI-rM0l2N3ssRa1QUEQPnkI2O0tT2t2abBX_vSkteBqYed534GHsCuEOAcr7CCCEzgBkBoWqMnXExqikyBAUHrNxOmBWVCWM2FmMSwDMK5CnbISikqUu1Zh9vtHKDr7v4sJveE3DD1HHp5-vcsKtG_y3H3657RpeB7Jx4M52jgKP2-hoM_jar3aAT5GF7ygSn9mO__Rr6i7YSWtXkS4P85x9PD68T2fZ_OXpeTqZZ04JGDIC0uigkBIEoLBOaqyd0E3l0oK0s0rXTjcFNi2gK9tCFiDzmqhRMiHynN3sezeh_9pSHMyy34YuvTQCldKiBJkg3EMu9DEGas0m-LUNvwbB7FyavUuTlJmdS6NS5vpQvK3X1PwnDvIScHsAbHR21Ybkxsd_Lsc817mQf7A5e2U</recordid><startdate>20030901</startdate><enddate>20030901</enddate><creator>PING HUANG</creator><creator>BING ZHU</creator><creator>WANG, Lian-Sheng</creator><creator>OUYANG, Dong-Sheng</creator><creator>HUANG, Song-Lin</creator><creator>CHEN, Xiao-Ping</creator><creator>ZHOU, Hong-Hao</creator><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20030901</creationdate><title>Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women</title><author>PING HUANG ; BING ZHU ; WANG, Lian-Sheng ; OUYANG, Dong-Sheng ; HUANG, Song-Lin ; CHEN, Xiao-Ping ; ZHOU, Hong-Hao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-e0e81c063302012ac381bc28d9c020e8ca48bc8d61df01c7f636035beed43c023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>Asian Continental Ancestry Group</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - ethnology</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>China</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Disease Susceptibility</topic><topic>Female</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Midazolam - analogs & derivatives</topic><topic>Midazolam - blood</topic><topic>Midazolam - metabolism</topic><topic>Oxidoreductases, N-Demethylating - genetics</topic><topic>Oxidoreductases, N-Demethylating - metabolism</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, Progesterone - metabolism</topic><topic>Risk Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PING HUANG</creatorcontrib><creatorcontrib>BING ZHU</creatorcontrib><creatorcontrib>WANG, Lian-Sheng</creatorcontrib><creatorcontrib>OUYANG, Dong-Sheng</creatorcontrib><creatorcontrib>HUANG, Song-Lin</creatorcontrib><creatorcontrib>CHEN, Xiao-Ping</creatorcontrib><creatorcontrib>ZHOU, Hong-Hao</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>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PING HUANG</au><au>BING ZHU</au><au>WANG, Lian-Sheng</au><au>OUYANG, Dong-Sheng</au><au>HUANG, Song-Lin</au><au>CHEN, Xiao-Ping</au><au>ZHOU, Hong-Hao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women</atitle><jtitle>European journal of clinical pharmacology</jtitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2003-09-01</date><risdate>2003</risdate><volume>59</volume><issue>5-6</issue><spage>471</spage><epage>476</epage><pages>471-476</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Breast cancer is the most frequent type of tumor in women. The main cause of breast cancer remains unknown. Extensive studies have shown that endogenous steroid hormones, especially estrogens, are important in the development and the progression of breast cancer, and the carcinogenesis of estrogens is related to their major oxidative metabolites, 16alpha-hydroxyestrogens and 4-hydroxyestrogens. CYP3A plays a major role in the 4- and 16alpha-hydroxylation of estrogens. Furthermore, CYP3A is present in human mammary epithelial cells and expressed higher and more frequently in malignant breast cells than in the adjacent normal breast tissue. Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility.
To evaluate the relationship of CYP3A activity to breast cancer susceptibility in Chinese Han women using the plasma 1-hydroxymidazolam (1-OHMDZ) to midazolam (MDZ) ratio as the marker of CYP3A activity.
One hundred and twenty-nine Chinese Han female breast tumor patients and 121 healthy unrelated female volunteers were enrolled in the current study. After an overnight fast, each subject was administered a single oral dose (7.5 mg) of midazolam. Blood samples (5 ml) were drawn at 1 h after the drug administration. The concentration of parent MDZ and its major metabolite 1-OH-MDZ was measured in all the plasma samples using high-performance liquid chromatography.
Complete chromatographic data on plasma ratios of 1-OHMDZ to MDZ for 103 cases of breast cancer and 114 controls were available. The plasma concentration ratios of 1-OHMDZ to MDZ were 0.4520+/-0.2318 and 0.3298+/-0.1610 for the malignant cases and the controls, respectively. A higher CYP3A activity was found in the breast cancer cases than in the controls ( P<0.001), and the CYP3A activity of patients with lymph-node metastasis was higher than that of patients without lymph-node metastasis ( P=0.028). CYP3A activity in estrogen receptor or progesterone receptor positive cases was the same as in estrogen receptor or progesterone receptor negative cases ( P=0.124, 0.175).
Our results indicate that high CYP3A activity may contribute to breast cancer disease genesis and may promote breast cancer to lymph-node metastasis.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>12937874</pmid><doi>10.1007/s00228-003-0649-4</doi><tpages>6</tpages></addata></record> |
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| subjects | Aryl Hydrocarbon Hydroxylases - genetics Aryl Hydrocarbon Hydroxylases - metabolism Asian Continental Ancestry Group Biological and medical sciences Breast cancer Breast Neoplasms - ethnology Breast Neoplasms - metabolism Breast Neoplasms - pathology China Cytochrome P-450 CYP3A Disease Susceptibility Female Gynecology. Andrology. Obstetrics Humans Lymphatic Metastasis Mammary gland diseases Medical sciences Midazolam - analogs & derivatives Midazolam - blood Midazolam - metabolism Oxidoreductases, N-Demethylating - genetics Oxidoreductases, N-Demethylating - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Risk Factors Tumors |
| title | Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women |
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