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Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set
Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (...
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| Published in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2007-12, Vol.16 (12), p.2557-2565 |
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| creator | BEESLEY, Jonathan JORDAN, Susan J GAYTHER, Simon A PHAROAH, Paul D. P WEBB, Penelope M CHENEVIX-TRENCH, Georgia SPURDLE, Amanda B HONGLIN SONG RAMUS, Susan J KRUGER KJAER, Suzanne HOGDALL, Estrid DICIOCCIO, Richard A MCGUIRE, Valerie WHITTEMORE, Alice S |
| description | Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that
confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP)
in genes involved in steroid hormone synthesis ( SRD5A2, CYP19A1, HSB17B1, and HSD17B4 ) and DNA repair ( XRCC2, XRCC3, BRCA2, and RAD52 ) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian
origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated
with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele ( P = 0.00002). We then genotyped another SNP in this gene (rs632148; r 2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United
Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples,
and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this
gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2557–9) |
| doi_str_mv | 10.1158/1055-9965.EPI-07-0542 |
| format | article |
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confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP)
in genes involved in steroid hormone synthesis ( SRD5A2, CYP19A1, HSB17B1, and HSD17B4 ) and DNA repair ( XRCC2, XRCC3, BRCA2, and RAD52 ) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian
origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated
with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele ( P = 0.00002). We then genotyped another SNP in this gene (rs632148; r 2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United
Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples,
and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this
gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2557–9)</description><identifier>ISSN: 1055-9965</identifier><identifier>EISSN: 1538-7755</identifier><identifier>DOI: 10.1158/1055-9965.EPI-07-0542</identifier><identifier>PMID: 18086758</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics ; Australia ; Biological and medical sciences ; Case-Control Studies ; DNA Repair - genetics ; DNA Repair Enzymes - genetics ; DNA repair genes ; Female ; Female genital diseases ; Genetic Predisposition to Disease ; Genotype ; Gonadal Steroid Hormones - genetics ; Gonadal Steroid Hormones - metabolism ; Gynecology. Andrology. Obstetrics ; hormone metabolism genes ; Humans ; Medical sciences ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - metabolism ; ovarian cancer ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Polymorphism, Single Nucleotide ; Reproducibility of Results ; Risk Factors ; SNP ; Tropical medicine ; Tumors</subject><ispartof>Cancer epidemiology, biomarkers & prevention, 2007-12, Vol.16 (12), p.2557-2565</ispartof><rights>2008 INIST-CNRS</rights><rights>Copyright © 2007 American Association for Cancer Research. 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-25f1efff6c4e13f0f65f3e62127a6e622848a508e1ea4ce9bf5e20994b3259ed3</citedby><cites>FETCH-LOGICAL-c504t-25f1efff6c4e13f0f65f3e62127a6e622848a508e1ea4ce9bf5e20994b3259ed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20009865$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18086758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BEESLEY, Jonathan</creatorcontrib><creatorcontrib>JORDAN, Susan J</creatorcontrib><creatorcontrib>GAYTHER, Simon A</creatorcontrib><creatorcontrib>PHAROAH, Paul D. P</creatorcontrib><creatorcontrib>WEBB, Penelope M</creatorcontrib><creatorcontrib>CHENEVIX-TRENCH, Georgia</creatorcontrib><creatorcontrib>SPURDLE, Amanda B</creatorcontrib><creatorcontrib>HONGLIN SONG</creatorcontrib><creatorcontrib>RAMUS, Susan J</creatorcontrib><creatorcontrib>KRUGER KJAER, Suzanne</creatorcontrib><creatorcontrib>HOGDALL, Estrid</creatorcontrib><creatorcontrib>DICIOCCIO, Richard A</creatorcontrib><creatorcontrib>MCGUIRE, Valerie</creatorcontrib><creatorcontrib>WHITTEMORE, Alice S</creatorcontrib><creatorcontrib>Australian Breast Cancer Family Study</creatorcontrib><creatorcontrib>Australian Ovarian Cancer Study Group</creatorcontrib><creatorcontrib>Australian Cancer Study (Ovarian Cancer)</creatorcontrib><creatorcontrib>Australian Ovarian Cancer Study Group</creatorcontrib><creatorcontrib>Australian Cancer Study (Ovarian Cancer)</creatorcontrib><creatorcontrib>Australian Breast Cancer Family Study</creatorcontrib><title>Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set</title><title>Cancer epidemiology, biomarkers & prevention</title><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><description>Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that
confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP)
in genes involved in steroid hormone synthesis ( SRD5A2, CYP19A1, HSB17B1, and HSD17B4 ) and DNA repair ( XRCC2, XRCC3, BRCA2, and RAD52 ) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian
origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated
with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele ( P = 0.00002). We then genotyped another SNP in this gene (rs632148; r 2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United
Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples,
and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this
gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2557–9)</description><subject>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics</subject><subject>Australia</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>DNA Repair - genetics</subject><subject>DNA Repair Enzymes - genetics</subject><subject>DNA repair genes</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Gonadal Steroid Hormones - genetics</subject><subject>Gonadal Steroid Hormones - metabolism</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>hormone metabolism genes</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Neoplasms, Glandular and Epithelial - genetics</subject><subject>Neoplasms, Glandular and Epithelial - metabolism</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Reproducibility of Results</subject><subject>Risk Factors</subject><subject>SNP</subject><subject>Tropical medicine</subject><subject>Tumors</subject><issn>1055-9965</issn><issn>1538-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqFksFu1DAQhiMEoqXwCCBfQOKQYjuxk3CotCxLW6m0FVu4Wl5nvDFy7MVOuurr8WQ43aXAidPY429-_db8WfaS4GNCWP2OYMbypuHseHF9nuMqx6ykj7JDwoo6ryrGHqfzb-Ygexbjd4xx1TD2NDsgNa55xerD7OcsRq-MHIx36AMMWwCHlsatLeSXo7LgB9MCuvb2rvdh05nYR2QcOvOh9w7QZxjkytvURtK16OPlDH2BjTQBnYKDeN9cbMzQgTXSoqtbGYx0aC6dgvA-sXG0Q0Q6-B7dbD2ajXEI0k7Mchhbs5dI11nbmsllUvmWgHZneQnD8-yJljbCi309yr5-WtzMz_KLq9Pz-ewiVwyXQ06ZJqC15qoEUmisOdMFcEpoJXmqtC5ryXANBGSpoFlpBhQ3TbkqKGugLY6yk53uZlz10Cpwk1OxCaaX4U54acS_L850Yu1vBeWck7pKAm_2AsH_GCEOojdRgbXSgR-j4A3mTcX4f0GK0-4IaxLIdqAKPsYA-sENwWKKiZgiIKYIiBQTgSsxxSTNvfr7K3-m9rlIwOs9IKOSVoe0LxMfOJqi1NScJe7tjuvMutuaAELdbzZABBlUJwgXhArKWFX8AtbU2T4</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>BEESLEY, Jonathan</creator><creator>JORDAN, Susan J</creator><creator>GAYTHER, Simon A</creator><creator>PHAROAH, Paul D. 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P ; WEBB, Penelope M ; CHENEVIX-TRENCH, Georgia ; SPURDLE, Amanda B ; HONGLIN SONG ; RAMUS, Susan J ; KRUGER KJAER, Suzanne ; HOGDALL, Estrid ; DICIOCCIO, Richard A ; MCGUIRE, Valerie ; WHITTEMORE, Alice S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-25f1efff6c4e13f0f65f3e62127a6e622848a508e1ea4ce9bf5e20994b3259ed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics</topic><topic>Australia</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>DNA Repair - genetics</topic><topic>DNA Repair Enzymes - genetics</topic><topic>DNA repair genes</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Gonadal Steroid Hormones - genetics</topic><topic>Gonadal Steroid Hormones - metabolism</topic><topic>Gynecology. 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P</au><au>WEBB, Penelope M</au><au>CHENEVIX-TRENCH, Georgia</au><au>SPURDLE, Amanda B</au><au>HONGLIN SONG</au><au>RAMUS, Susan J</au><au>KRUGER KJAER, Suzanne</au><au>HOGDALL, Estrid</au><au>DICIOCCIO, Richard A</au><au>MCGUIRE, Valerie</au><au>WHITTEMORE, Alice S</au><aucorp>Australian Breast Cancer Family Study</aucorp><aucorp>Australian Ovarian Cancer Study Group</aucorp><aucorp>Australian Cancer Study (Ovarian Cancer)</aucorp><aucorp>Australian Ovarian Cancer Study Group</aucorp><aucorp>Australian Cancer Study (Ovarian Cancer)</aucorp><aucorp>Australian Breast Cancer Family Study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set</atitle><jtitle>Cancer epidemiology, biomarkers & prevention</jtitle><addtitle>Cancer Epidemiol Biomarkers Prev</addtitle><date>2007-12-01</date><risdate>2007</risdate><volume>16</volume><issue>12</issue><spage>2557</spage><epage>2565</epage><pages>2557-2565</pages><issn>1055-9965</issn><eissn>1538-7755</eissn><abstract>Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that
confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP)
in genes involved in steroid hormone synthesis ( SRD5A2, CYP19A1, HSB17B1, and HSD17B4 ) and DNA repair ( XRCC2, XRCC3, BRCA2, and RAD52 ) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian
origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated
with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele ( P = 0.00002). We then genotyped another SNP in this gene (rs632148; r 2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United
Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples,
and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this
gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2557–9)</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18086758</pmid><doi>10.1158/1055-9965.EPI-07-0542</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer epidemiology, biomarkers & prevention, 2007-12, Vol.16 (12), p.2557-2565 |
| issn | 1055-9965 1538-7755 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2666187 |
| source | EZB Electronic Journals Library |
| subjects | 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics Australia Biological and medical sciences Case-Control Studies DNA Repair - genetics DNA Repair Enzymes - genetics DNA repair genes Female Female genital diseases Genetic Predisposition to Disease Genotype Gonadal Steroid Hormones - genetics Gonadal Steroid Hormones - metabolism Gynecology. Andrology. Obstetrics hormone metabolism genes Humans Medical sciences Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - metabolism ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Polymorphism, Single Nucleotide Reproducibility of Results Risk Factors SNP Tropical medicine Tumors |
| title | Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set |
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