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Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk
Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage a...
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| Published in: | PloS one 2015-06, Vol.10 (6), p.e0128106 |
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| creator | Chornokur, Ganna Lin, Hui-Yi Tyrer, Jonathan P Lawrenson, Kate Dennis, Joe Amankwah, Ernest K Qu, Xiaotao Tsai, Ya-Yu Jim, Heather S L Chen, Zhihua Chen, Ann Y Permuth-Wey, Jennifer Aben, Katja K H Anton-Culver, Hoda Antonenkova, Natalia Bruinsma, Fiona Bandera, Elisa V Bean, Yukie T Beckmann, Matthias W Bisogna, Maria Bjorge, Line Bogdanova, Natalia Brinton, Louise A Brooks-Wilson, Angela Bunker, Clareann H Butzow, Ralf Campbell, Ian G Carty, Karen Chang-Claude, Jenny Cook, Linda S Cramer, Daniel W Cunningham, Julie M Cybulski, Cezary Dansonka-Mieszkowska, Agnieszka du Bois, Andreas Despierre, Evelyn Dicks, Ed Doherty, Jennifer A Dörk, Thilo Dürst, Matthias Easton, Douglas F Eccles, Diana M Edwards, Robert P Ekici, Arif B Fasching, Peter A Fridley, Brooke L Gao, Yu-Tang Gentry-Maharaj, Aleksandra Giles, Graham G Glasspool, Rosalind Goodman, Marc T Gronwald, Jacek Harrington, Patricia Harter, Philipp Hein, Alexander Heitz, Florian Hildebrandt, Michelle A T Hillemanns, Peter Hogdall, Claus K Hogdall, Estrid Hosono, Satoyo Jakubowska, Anna Jensen, Allan Ji, Bu-Tian Karlan, Beth Y Kelemen, Linda E Kellar, Mellissa Kiemeney, Lambertus A Krakstad, Camilla Kjaer, Susanne K Kupryjanczyk, Jolanta Lambrechts, Diether Lambrechts, Sandrina Le, Nhu D Lee, Alice W Lele, Shashi Leminen, Arto Lester, Jenny Levine, Douglas A Liang, Dong Lim, Boon Kiong Lissowska, Jolanta Lu, Karen Lubinski, Jan Lundvall, Lene Massuger, Leon F A G Matsuo, Keitaro McGuire, Valerie McLaughlin, John R McNeish, Iain Menon, Usha Milne, Roger L Modugno, Francesmary Moysich, Kirsten B Ness, Roberta B Nevanlinna, Heli Eilber, Ursula Odunsi, Kunle Olson, Sara H Orlow, Irene |
| description | Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.
In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q |
| doi_str_mv | 10.1371/journal.pone.0128106 |
| format | article |
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Lin, Hui-Yi ; Tyrer, Jonathan P ; Lawrenson, Kate ; Dennis, Joe ; Amankwah, Ernest K ; Qu, Xiaotao ; Tsai, Ya-Yu ; Jim, Heather S L ; Chen, Zhihua ; Chen, Ann Y ; Permuth-Wey, Jennifer ; Aben, Katja K H ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Bruinsma, Fiona ; Bandera, Elisa V ; Bean, Yukie T ; Beckmann, Matthias W ; Bisogna, Maria ; Bjorge, Line ; Bogdanova, Natalia ; Brinton, Louise A ; Brooks-Wilson, Angela ; Bunker, Clareann H ; Butzow, Ralf ; Campbell, Ian G ; Carty, Karen ; Chang-Claude, Jenny ; Cook, Linda S ; Cramer, Daniel W ; Cunningham, Julie M ; Cybulski, Cezary ; Dansonka-Mieszkowska, Agnieszka ; du Bois, Andreas ; Despierre, Evelyn ; Dicks, Ed ; Doherty, Jennifer A ; Dörk, Thilo ; Dürst, Matthias ; Easton, Douglas F ; Eccles, Diana M ; Edwards, Robert P ; Ekici, Arif B ; Fasching, Peter A ; Fridley, Brooke L ; Gao, Yu-Tang ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goodman, Marc T ; Gronwald, Jacek ; Harrington, Patricia ; Harter, Philipp ; Hein, Alexander ; Heitz, Florian ; Hildebrandt, Michelle A T ; Hillemanns, Peter ; Hogdall, Claus K ; Hogdall, Estrid ; Hosono, Satoyo ; Jakubowska, Anna ; Jensen, Allan ; Ji, Bu-Tian ; Karlan, Beth Y ; Kelemen, Linda E ; Kellar, Mellissa ; Kiemeney, Lambertus A ; Krakstad, Camilla ; Kjaer, Susanne K ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Lambrechts, Sandrina ; Le, Nhu D ; Lee, Alice W ; Lele, Shashi ; Leminen, Arto ; Lester, Jenny ; Levine, Douglas A ; Liang, Dong ; Lim, Boon Kiong ; Lissowska, Jolanta ; Lu, Karen ; Lubinski, Jan ; Lundvall, Lene ; Massuger, Leon F A G ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R ; McNeish, Iain ; Menon, Usha ; Milne, Roger L ; Modugno, Francesmary ; Moysich, Kirsten B ; Ness, Roberta B ; Nevanlinna, Heli ; Eilber, Ursula ; Odunsi, Kunle ; Olson, Sara H ; Orlow, Irene</creator><contributor>Agoulnik, Irina U</contributor><creatorcontrib>Chornokur, Ganna ; Lin, Hui-Yi ; Tyrer, Jonathan P ; Lawrenson, Kate ; Dennis, Joe ; Amankwah, Ernest K ; Qu, Xiaotao ; Tsai, Ya-Yu ; Jim, Heather S L ; Chen, Zhihua ; Chen, Ann Y ; Permuth-Wey, Jennifer ; Aben, Katja K H ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Bruinsma, Fiona ; Bandera, Elisa V ; Bean, Yukie T ; Beckmann, Matthias W ; Bisogna, Maria ; Bjorge, Line ; Bogdanova, Natalia ; Brinton, Louise A ; Brooks-Wilson, Angela ; Bunker, Clareann H ; Butzow, Ralf ; Campbell, Ian G ; Carty, Karen ; Chang-Claude, Jenny ; Cook, Linda S ; Cramer, Daniel W ; Cunningham, Julie M ; Cybulski, Cezary ; Dansonka-Mieszkowska, Agnieszka ; du Bois, Andreas ; Despierre, Evelyn ; Dicks, Ed ; Doherty, Jennifer A ; Dörk, Thilo ; Dürst, Matthias ; Easton, Douglas F ; Eccles, Diana M ; Edwards, Robert P ; Ekici, Arif B ; Fasching, Peter A ; Fridley, Brooke L ; Gao, Yu-Tang ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goodman, Marc T ; Gronwald, Jacek ; Harrington, Patricia ; Harter, Philipp ; Hein, Alexander ; Heitz, Florian ; Hildebrandt, Michelle A T ; Hillemanns, Peter ; Hogdall, Claus K ; Hogdall, Estrid ; Hosono, Satoyo ; Jakubowska, Anna ; Jensen, Allan ; Ji, Bu-Tian ; Karlan, Beth Y ; Kelemen, Linda E ; Kellar, Mellissa ; Kiemeney, Lambertus A ; Krakstad, Camilla ; Kjaer, Susanne K ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Lambrechts, Sandrina ; Le, Nhu D ; Lee, Alice W ; Lele, Shashi ; Leminen, Arto ; Lester, Jenny ; Levine, Douglas A ; Liang, Dong ; Lim, Boon Kiong ; Lissowska, Jolanta ; Lu, Karen ; Lubinski, Jan ; Lundvall, Lene ; Massuger, Leon F A G ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R ; McNeish, Iain ; Menon, Usha ; Milne, Roger L ; Modugno, Francesmary ; Moysich, Kirsten B ; Ness, Roberta B ; Nevanlinna, Heli ; Eilber, Ursula ; Odunsi, Kunle ; Olson, Sara H ; Orlow, Irene ; AOCS management group ; Georgia Chenevix-Trench ; Georgia Chenevix-Trench on behalf of the AOCS management group ; Agoulnik, Irina U</creatorcontrib><description>Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.
In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0128106</identifier><identifier>PMID: 26091520</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alleles ; Asian ; Bioinformatics ; Biological Transport ; Black or African American ; Breast cancer ; Cancer ; Carcinoma, Ovarian Epithelial ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Case-Control Studies ; Consortia ; Deoxyribonucleic acid ; DNA ; DNA damage ; Epidemiology ; Female ; Gene expression ; Genes ; Genetic Association Studies ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic Variation ; Genetics ; Genomes ; Gynecology ; Health care ; Health risks ; Health sciences ; Hormones ; Hospitals ; Humans ; Invasiveness ; Iron ; Laboratories ; Medical research ; Meta-analysis ; Molecular chains ; Neoplasms, Glandular and Epithelial - epidemiology ; Neoplasms, Glandular and Epithelial - genetics ; Neoplasms, Glandular and Epithelial - pathology ; Obstetrics ; Odds Ratio ; Oncology ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - epidemiology ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Oxygen ; Pathology ; Polymorphism, Single Nucleotide ; Population ; Prevention ; Preventive medicine ; Public health ; Reactive oxygen species ; Regression analysis ; Regression models ; Risk ; Single-nucleotide polymorphism ; Thyroid gland ; Trace elements ; Transport processes ; Tumors</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0128106</ispartof><rights>2015 Chornokur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Chornokur et al 2015 Chornokur et 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MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Agoulnik, Irina U</contributor><creatorcontrib>Chornokur, Ganna</creatorcontrib><creatorcontrib>Lin, Hui-Yi</creatorcontrib><creatorcontrib>Tyrer, Jonathan P</creatorcontrib><creatorcontrib>Lawrenson, Kate</creatorcontrib><creatorcontrib>Dennis, Joe</creatorcontrib><creatorcontrib>Amankwah, Ernest K</creatorcontrib><creatorcontrib>Qu, Xiaotao</creatorcontrib><creatorcontrib>Tsai, Ya-Yu</creatorcontrib><creatorcontrib>Jim, Heather S L</creatorcontrib><creatorcontrib>Chen, Zhihua</creatorcontrib><creatorcontrib>Chen, Ann Y</creatorcontrib><creatorcontrib>Permuth-Wey, Jennifer</creatorcontrib><creatorcontrib>Aben, Katja K H</creatorcontrib><creatorcontrib>Anton-Culver, Hoda</creatorcontrib><creatorcontrib>Antonenkova, Natalia</creatorcontrib><creatorcontrib>Bruinsma, Fiona</creatorcontrib><creatorcontrib>Bandera, Elisa V</creatorcontrib><creatorcontrib>Bean, Yukie T</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Bisogna, Maria</creatorcontrib><creatorcontrib>Bjorge, Line</creatorcontrib><creatorcontrib>Bogdanova, Natalia</creatorcontrib><creatorcontrib>Brinton, Louise A</creatorcontrib><creatorcontrib>Brooks-Wilson, Angela</creatorcontrib><creatorcontrib>Bunker, Clareann H</creatorcontrib><creatorcontrib>Butzow, Ralf</creatorcontrib><creatorcontrib>Campbell, Ian G</creatorcontrib><creatorcontrib>Carty, Karen</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Cook, Linda S</creatorcontrib><creatorcontrib>Cramer, Daniel W</creatorcontrib><creatorcontrib>Cunningham, Julie M</creatorcontrib><creatorcontrib>Cybulski, Cezary</creatorcontrib><creatorcontrib>Dansonka-Mieszkowska, Agnieszka</creatorcontrib><creatorcontrib>du Bois, Andreas</creatorcontrib><creatorcontrib>Despierre, Evelyn</creatorcontrib><creatorcontrib>Dicks, Ed</creatorcontrib><creatorcontrib>Doherty, Jennifer A</creatorcontrib><creatorcontrib>Dörk, Thilo</creatorcontrib><creatorcontrib>Dürst, Matthias</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Eccles, Diana M</creatorcontrib><creatorcontrib>Edwards, Robert P</creatorcontrib><creatorcontrib>Ekici, Arif B</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Fridley, Brooke L</creatorcontrib><creatorcontrib>Gao, Yu-Tang</creatorcontrib><creatorcontrib>Gentry-Maharaj, Aleksandra</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Glasspool, Rosalind</creatorcontrib><creatorcontrib>Goodman, Marc T</creatorcontrib><creatorcontrib>Gronwald, Jacek</creatorcontrib><creatorcontrib>Harrington, Patricia</creatorcontrib><creatorcontrib>Harter, Philipp</creatorcontrib><creatorcontrib>Hein, Alexander</creatorcontrib><creatorcontrib>Heitz, Florian</creatorcontrib><creatorcontrib>Hildebrandt, Michelle A T</creatorcontrib><creatorcontrib>Hillemanns, Peter</creatorcontrib><creatorcontrib>Hogdall, Claus K</creatorcontrib><creatorcontrib>Hogdall, Estrid</creatorcontrib><creatorcontrib>Hosono, Satoyo</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Jensen, Allan</creatorcontrib><creatorcontrib>Ji, Bu-Tian</creatorcontrib><creatorcontrib>Karlan, Beth Y</creatorcontrib><creatorcontrib>Kelemen, Linda E</creatorcontrib><creatorcontrib>Kellar, Mellissa</creatorcontrib><creatorcontrib>Kiemeney, Lambertus A</creatorcontrib><creatorcontrib>Krakstad, Camilla</creatorcontrib><creatorcontrib>Kjaer, Susanne K</creatorcontrib><creatorcontrib>Kupryjanczyk, Jolanta</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Lambrechts, Sandrina</creatorcontrib><creatorcontrib>Le, Nhu D</creatorcontrib><creatorcontrib>Lee, Alice W</creatorcontrib><creatorcontrib>Lele, Shashi</creatorcontrib><creatorcontrib>Leminen, Arto</creatorcontrib><creatorcontrib>Lester, Jenny</creatorcontrib><creatorcontrib>Levine, Douglas A</creatorcontrib><creatorcontrib>Liang, Dong</creatorcontrib><creatorcontrib>Lim, Boon Kiong</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Lu, Karen</creatorcontrib><creatorcontrib>Lubinski, Jan</creatorcontrib><creatorcontrib>Lundvall, Lene</creatorcontrib><creatorcontrib>Massuger, Leon F A G</creatorcontrib><creatorcontrib>Matsuo, Keitaro</creatorcontrib><creatorcontrib>McGuire, Valerie</creatorcontrib><creatorcontrib>McLaughlin, John R</creatorcontrib><creatorcontrib>McNeish, Iain</creatorcontrib><creatorcontrib>Menon, Usha</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Modugno, Francesmary</creatorcontrib><creatorcontrib>Moysich, Kirsten B</creatorcontrib><creatorcontrib>Ness, Roberta B</creatorcontrib><creatorcontrib>Nevanlinna, Heli</creatorcontrib><creatorcontrib>Eilber, Ursula</creatorcontrib><creatorcontrib>Odunsi, Kunle</creatorcontrib><creatorcontrib>Olson, Sara H</creatorcontrib><creatorcontrib>Orlow, Irene</creatorcontrib><creatorcontrib>AOCS management group</creatorcontrib><creatorcontrib>Georgia Chenevix-Trench</creatorcontrib><creatorcontrib>Georgia Chenevix-Trench on behalf of the AOCS management group</creatorcontrib><title>Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.
In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.</description><subject>Alleles</subject><subject>Asian</subject><subject>Bioinformatics</subject><subject>Biological Transport</subject><subject>Black or African American</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Carcinoma, Ovarian Epithelial</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Case-Control Studies</subject><subject>Consortia</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic Association Studies</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Gynecology</subject><subject>Health care</subject><subject>Health risks</subject><subject>Health sciences</subject><subject>Hormones</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Iron</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>Meta-analysis</subject><subject>Molecular chains</subject><subject>Neoplasms, Glandular and Epithelial - epidemiology</subject><subject>Neoplasms, Glandular and Epithelial - genetics</subject><subject>Neoplasms, Glandular and Epithelial - pathology</subject><subject>Obstetrics</subject><subject>Odds Ratio</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - epidemiology</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Oxygen</subject><subject>Pathology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Prevention</subject><subject>Preventive medicine</subject><subject>Public health</subject><subject>Reactive oxygen species</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Risk</subject><subject>Single-nucleotide polymorphism</subject><subject>Thyroid gland</subject><subject>Trace elements</subject><subject>Transport processes</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1r1TAYLqK4D_0HogVv5sU5JmnaJDeClOM8MDgg0zsJafJ26zFNuqQd-O-X7nRjE68S3ufj_eDJsncYrXHB8Oe9n4JTdj14B2uECceoepEdY1GQVUVQ8fLJ_yg7iXGPUFnwqnqdHZEKCVwSdJz9rn3fe5efg4Ox0_kvFTo1dqmydXkN1k5WhfwyKBcHH8Z7XsyVM_lm6MZrsJ2y-e52ViW-chpCfrbZ1Z_yH1388yZ71Sob4e3ynmY_v20u6--ri935tv56sdIlqcZVy0GZFnRbAmlJaQQlLW9Q0ZScaJOwhLScNwK4aAAxLSqqOWuAGsS4EcVp9uHgO1gf5XKZKHHFhRCEiiIxtgeG8Wovh9D1KvyVXnXyvuDDlVQhHcCCZLQFjhAzWCFqBBZKY-ANbRljumxY8vqydJuaHowGNwZln5k-R1x3La_8raSUUV6VyeBsMQj-ZoI4yr6LOh1bOfDTPLdAFeUCzb0-_kP9_3b0wNLBxxigfRwGIzmn5UEl57TIJS1J9v7pIo-ih3gUd-dKvlc</recordid><startdate>20150619</startdate><enddate>20150619</enddate><creator>Chornokur, Ganna</creator><creator>Lin, Hui-Yi</creator><creator>Tyrer, Jonathan P</creator><creator>Lawrenson, Kate</creator><creator>Dennis, Joe</creator><creator>Amankwah, Ernest K</creator><creator>Qu, Xiaotao</creator><creator>Tsai, Ya-Yu</creator><creator>Jim, Heather S L</creator><creator>Chen, Zhihua</creator><creator>Chen, Ann Y</creator><creator>Permuth-Wey, Jennifer</creator><creator>Aben, Katja K H</creator><creator>Anton-Culver, Hoda</creator><creator>Antonenkova, Natalia</creator><creator>Bruinsma, Fiona</creator><creator>Bandera, Elisa V</creator><creator>Bean, Yukie T</creator><creator>Beckmann, Matthias W</creator><creator>Bisogna, Maria</creator><creator>Bjorge, Line</creator><creator>Bogdanova, Natalia</creator><creator>Brinton, Louise A</creator><creator>Brooks-Wilson, Angela</creator><creator>Bunker, Clareann H</creator><creator>Butzow, Ralf</creator><creator>Campbell, Ian G</creator><creator>Carty, Karen</creator><creator>Chang-Claude, Jenny</creator><creator>Cook, Linda S</creator><creator>Cramer, Daniel W</creator><creator>Cunningham, Julie M</creator><creator>Cybulski, Cezary</creator><creator>Dansonka-Mieszkowska, Agnieszka</creator><creator>du Bois, Andreas</creator><creator>Despierre, Evelyn</creator><creator>Dicks, Ed</creator><creator>Doherty, Jennifer A</creator><creator>Dörk, Thilo</creator><creator>Dürst, Matthias</creator><creator>Easton, Douglas F</creator><creator>Eccles, Diana M</creator><creator>Edwards, Robert P</creator><creator>Ekici, Arif B</creator><creator>Fasching, Peter A</creator><creator>Fridley, Brooke L</creator><creator>Gao, Yu-Tang</creator><creator>Gentry-Maharaj, Aleksandra</creator><creator>Giles, Graham G</creator><creator>Glasspool, Rosalind</creator><creator>Goodman, Marc T</creator><creator>Gronwald, Jacek</creator><creator>Harrington, Patricia</creator><creator>Harter, Philipp</creator><creator>Hein, Alexander</creator><creator>Heitz, Florian</creator><creator>Hildebrandt, Michelle A T</creator><creator>Hillemanns, Peter</creator><creator>Hogdall, Claus K</creator><creator>Hogdall, Estrid</creator><creator>Hosono, Satoyo</creator><creator>Jakubowska, Anna</creator><creator>Jensen, Allan</creator><creator>Ji, Bu-Tian</creator><creator>Karlan, Beth Y</creator><creator>Kelemen, Linda E</creator><creator>Kellar, Mellissa</creator><creator>Kiemeney, Lambertus A</creator><creator>Krakstad, Camilla</creator><creator>Kjaer, Susanne K</creator><creator>Kupryjanczyk, Jolanta</creator><creator>Lambrechts, Diether</creator><creator>Lambrechts, Sandrina</creator><creator>Le, Nhu D</creator><creator>Lee, Alice W</creator><creator>Lele, Shashi</creator><creator>Leminen, Arto</creator><creator>Lester, Jenny</creator><creator>Levine, Douglas A</creator><creator>Liang, Dong</creator><creator>Lim, Boon Kiong</creator><creator>Lissowska, Jolanta</creator><creator>Lu, Karen</creator><creator>Lubinski, Jan</creator><creator>Lundvall, Lene</creator><creator>Massuger, Leon F A G</creator><creator>Matsuo, Keitaro</creator><creator>McGuire, Valerie</creator><creator>McLaughlin, John R</creator><creator>McNeish, 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(PLoS)</general><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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150619</creationdate><title>Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk</title><author>Chornokur, Ganna ; Lin, Hui-Yi ; Tyrer, Jonathan P ; Lawrenson, Kate ; Dennis, Joe ; Amankwah, Ernest K ; Qu, Xiaotao ; Tsai, Ya-Yu ; Jim, Heather S L ; Chen, Zhihua ; Chen, Ann Y ; Permuth-Wey, Jennifer ; Aben, Katja K H ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Bruinsma, Fiona ; Bandera, Elisa V ; Bean, Yukie T ; Beckmann, Matthias W ; Bisogna, Maria ; Bjorge, Line ; Bogdanova, Natalia ; Brinton, Louise A ; Brooks-Wilson, Angela ; Bunker, Clareann H ; Butzow, Ralf ; Campbell, Ian G ; Carty, Karen ; Chang-Claude, Jenny ; Cook, Linda S ; Cramer, Daniel W ; Cunningham, Julie M ; Cybulski, Cezary ; Dansonka-Mieszkowska, Agnieszka ; du Bois, Andreas ; Despierre, Evelyn ; Dicks, Ed ; Doherty, Jennifer A ; Dörk, Thilo ; Dürst, Matthias ; Easton, Douglas F ; Eccles, Diana M ; Edwards, Robert P ; Ekici, Arif B ; Fasching, Peter A ; Fridley, Brooke L ; Gao, Yu-Tang ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goodman, Marc T ; Gronwald, Jacek ; Harrington, Patricia ; Harter, Philipp ; Hein, Alexander ; Heitz, Florian ; Hildebrandt, Michelle A T ; Hillemanns, Peter ; Hogdall, Claus K ; Hogdall, Estrid ; Hosono, Satoyo ; Jakubowska, Anna ; Jensen, Allan ; Ji, Bu-Tian ; Karlan, Beth Y ; Kelemen, Linda E ; Kellar, Mellissa ; Kiemeney, Lambertus A ; Krakstad, Camilla ; Kjaer, Susanne K ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Lambrechts, Sandrina ; Le, Nhu D ; Lee, Alice W ; Lele, Shashi ; Leminen, Arto ; Lester, Jenny ; Levine, Douglas A ; Liang, Dong ; Lim, Boon Kiong ; Lissowska, Jolanta ; Lu, Karen ; Lubinski, Jan ; Lundvall, Lene ; Massuger, Leon F A G ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R ; McNeish, Iain ; Menon, Usha ; Milne, Roger L ; Modugno, Francesmary ; Moysich, Kirsten B ; Ness, Roberta B ; Nevanlinna, Heli ; Eilber, Ursula ; Odunsi, Kunle ; Olson, Sara H ; Orlow, Irene</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-f8eadfecf5e2f25d942f8b03b582cdeadcf5f88b9e89be07c964c87be4d078d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Alleles</topic><topic>Asian</topic><topic>Bioinformatics</topic><topic>Biological Transport</topic><topic>Black or African American</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Carcinoma, Ovarian Epithelial</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Case-Control Studies</topic><topic>Consortia</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic Association Studies</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Gynecology</topic><topic>Health care</topic><topic>Health risks</topic><topic>Health sciences</topic><topic>Hormones</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Invasiveness</topic><topic>Iron</topic><topic>Laboratories</topic><topic>Medical research</topic><topic>Meta-analysis</topic><topic>Molecular chains</topic><topic>Neoplasms, Glandular and Epithelial - epidemiology</topic><topic>Neoplasms, Glandular and Epithelial - genetics</topic><topic>Neoplasms, Glandular and Epithelial - pathology</topic><topic>Obstetrics</topic><topic>Odds Ratio</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - epidemiology</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Oxygen</topic><topic>Pathology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Prevention</topic><topic>Preventive medicine</topic><topic>Public health</topic><topic>Reactive oxygen species</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Risk</topic><topic>Single-nucleotide polymorphism</topic><topic>Thyroid gland</topic><topic>Trace elements</topic><topic>Transport processes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chornokur, Ganna</creatorcontrib><creatorcontrib>Lin, Hui-Yi</creatorcontrib><creatorcontrib>Tyrer, Jonathan P</creatorcontrib><creatorcontrib>Lawrenson, Kate</creatorcontrib><creatorcontrib>Dennis, Joe</creatorcontrib><creatorcontrib>Amankwah, Ernest K</creatorcontrib><creatorcontrib>Qu, Xiaotao</creatorcontrib><creatorcontrib>Tsai, Ya-Yu</creatorcontrib><creatorcontrib>Jim, Heather S L</creatorcontrib><creatorcontrib>Chen, Zhihua</creatorcontrib><creatorcontrib>Chen, Ann 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Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chornokur, Ganna</au><au>Lin, Hui-Yi</au><au>Tyrer, Jonathan P</au><au>Lawrenson, Kate</au><au>Dennis, Joe</au><au>Amankwah, Ernest K</au><au>Qu, Xiaotao</au><au>Tsai, Ya-Yu</au><au>Jim, Heather S L</au><au>Chen, Zhihua</au><au>Chen, Ann Y</au><au>Permuth-Wey, Jennifer</au><au>Aben, Katja K H</au><au>Anton-Culver, Hoda</au><au>Antonenkova, Natalia</au><au>Bruinsma, Fiona</au><au>Bandera, Elisa V</au><au>Bean, Yukie T</au><au>Beckmann, Matthias W</au><au>Bisogna, Maria</au><au>Bjorge, Line</au><au>Bogdanova, Natalia</au><au>Brinton, Louise A</au><au>Brooks-Wilson, Angela</au><au>Bunker, Clareann H</au><au>Butzow, Ralf</au><au>Campbell, Ian G</au><au>Carty, Karen</au><au>Chang-Claude, Jenny</au><au>Cook, Linda S</au><au>Cramer, Daniel W</au><au>Cunningham, Julie M</au><au>Cybulski, Cezary</au><au>Dansonka-Mieszkowska, Agnieszka</au><au>du Bois, Andreas</au><au>Despierre, Evelyn</au><au>Dicks, Ed</au><au>Doherty, Jennifer A</au><au>Dörk, Thilo</au><au>Dürst, Matthias</au><au>Easton, Douglas F</au><au>Eccles, Diana M</au><au>Edwards, Robert P</au><au>Ekici, Arif B</au><au>Fasching, Peter A</au><au>Fridley, Brooke L</au><au>Gao, Yu-Tang</au><au>Gentry-Maharaj, Aleksandra</au><au>Giles, Graham G</au><au>Glasspool, Rosalind</au><au>Goodman, Marc T</au><au>Gronwald, Jacek</au><au>Harrington, Patricia</au><au>Harter, Philipp</au><au>Hein, Alexander</au><au>Heitz, Florian</au><au>Hildebrandt, Michelle A T</au><au>Hillemanns, Peter</au><au>Hogdall, Claus K</au><au>Hogdall, Estrid</au><au>Hosono, Satoyo</au><au>Jakubowska, Anna</au><au>Jensen, Allan</au><au>Ji, Bu-Tian</au><au>Karlan, Beth Y</au><au>Kelemen, Linda E</au><au>Kellar, Mellissa</au><au>Kiemeney, Lambertus A</au><au>Krakstad, Camilla</au><au>Kjaer, Susanne K</au><au>Kupryjanczyk, Jolanta</au><au>Lambrechts, Diether</au><au>Lambrechts, Sandrina</au><au>Le, Nhu D</au><au>Lee, Alice W</au><au>Lele, Shashi</au><au>Leminen, Arto</au><au>Lester, Jenny</au><au>Levine, Douglas A</au><au>Liang, Dong</au><au>Lim, Boon Kiong</au><au>Lissowska, Jolanta</au><au>Lu, Karen</au><au>Lubinski, Jan</au><au>Lundvall, Lene</au><au>Massuger, Leon F A G</au><au>Matsuo, Keitaro</au><au>McGuire, Valerie</au><au>McLaughlin, John R</au><au>McNeish, Iain</au><au>Menon, Usha</au><au>Milne, Roger L</au><au>Modugno, Francesmary</au><au>Moysich, Kirsten B</au><au>Ness, Roberta B</au><au>Nevanlinna, Heli</au><au>Eilber, Ursula</au><au>Odunsi, Kunle</au><au>Olson, Sara H</au><au>Orlow, Irene</au><au>Agoulnik, Irina U</au><aucorp>AOCS management group</aucorp><aucorp>Georgia Chenevix-Trench</aucorp><aucorp>Georgia Chenevix-Trench on behalf of the AOCS management group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-06-19</date><risdate>2015</risdate><volume>10</volume><issue>6</issue><spage>e0128106</spage><pages>e0128106-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.
In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26091520</pmid><doi>10.1371/journal.pone.0128106</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-06, Vol.10 (6), p.e0128106 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1689992493 |
| source | PubMed (Medline); Publicly Available Content Database |
| subjects | Alleles Asian Bioinformatics Biological Transport Black or African American Breast cancer Cancer Carcinoma, Ovarian Epithelial Carrier Proteins - genetics Carrier Proteins - metabolism Case-Control Studies Consortia Deoxyribonucleic acid DNA DNA damage Epidemiology Female Gene expression Genes Genetic Association Studies Genetic diversity Genetic Predisposition to Disease Genetic Variation Genetics Genomes Gynecology Health care Health risks Health sciences Hormones Hospitals Humans Invasiveness Iron Laboratories Medical research Meta-analysis Molecular chains Neoplasms, Glandular and Epithelial - epidemiology Neoplasms, Glandular and Epithelial - genetics Neoplasms, Glandular and Epithelial - pathology Obstetrics Odds Ratio Oncology Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - epidemiology Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Oxygen Pathology Polymorphism, Single Nucleotide Population Prevention Preventive medicine Public health Reactive oxygen species Regression analysis Regression models Risk Single-nucleotide polymorphism Thyroid gland Trace elements Transport processes Tumors |
| title | Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk |
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