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Racine

Serveur d'exploration sur le lymphœdème

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Assessment of multifactor gene-environment interactions and ovarian cancer risk: Candidate genes, obesity, and hormone-related risk factors

Identifieur interne : 001393 ( Main/Exploration ); précédent : 001392; suivant : 001394

Assessment of multifactor gene-environment interactions and ovarian cancer risk: Candidate genes, obesity, and hormone-related risk factors

Auteurs : Joseph L. Usset ; Rama Raghavan ; Jonathan P. Tyrer [Royaume-Uni] ; Valerie Mcguire ; Weiva Sieh ; Penelope Webb ; Jenny Chang-Claude ; Anja Rudolph ; Hoda Anton-Culver ; Andrew Berchuck ; Louise Brinton ; Julie M. Cunningham ; Anna Defazio ; Jennifer A. Doherty ; Robert P. Edwards ; Simon A. Gayther ; Aleksandra Gentry-Maharaj [Royaume-Uni] ; Marc T. Goodman ; Estrid H Gdall ; Allan Jensen ; Sharon E. Johnatty ; Lambertus A. Kiemeney ; Susanne K. Kjaer ; Melissa C. Larson ; Galina Lurie ; Leon Massuger ; Usha Menon [Royaume-Uni] ; Francesmary Modugno [États-Unis] ; Kirsten B. Moysich ; Roberta B. Ness ; Malcolm C. Pike ; Susan J. Ramus [États-Unis] ; Mary Anne Rossing [États-Unis] ; Joseph Rothstein ; Honglin Song [Royaume-Uni] ; Pamela J. Thompson ; David J. Van Den Berg [États-Unis] ; Robert A. Vierkant ; Shan Wang-Gohrke [Allemagne] ; Nicolas Wentzensen ; Alice S. Whittemore ; Lynne R. Wilkens ; Anna H. Wu [États-Unis] ; Hannah Yang ; Celeste L. Pearce [États-Unis] ; Joellen M. Schildkraut ; Paul Pharoah [Royaume-Uni] ; Ellen L. Goode ; Brooke L. Fridley

Source :

RBID : PMC:4873330

Abstract

Background

Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure, and elevated estrogen levels are associated with obesity in post-menopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women.

Methods

We considered interactions between 11,441 single nucleotide polymorphisms (SNPs) within 80 candidate genes related to hormone biosynthesis & metabolism and insulin-like growth factors with six hormone-related factors: oral contraceptive use; parity; endometriosis; tubal ligation; hormone replacement therapy; and estrogen use; and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype specific analyses were also completed.

Results

SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, p = 4.9×10−6) and ESR1 (rs12661437, endometriosis, histology = all, p = 1.5×10−5). The most notable obesity - gene - hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, p = 8.8×10−6).

Conclusions

We have demonstrated the feasibility of assessing multi-factor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2. Future work is needed to develop powerful statistical methods able to detect these complex interactions.

Impact

Assessment of multifactor interaction is feasible, and, here, suggest that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility.


Url:
DOI: 10.1158/1055-9965.EPI-15-1039
PubMed: 26976855
PubMed Central: 4873330


Affiliations:

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<name sortKey="Sieh, Weiva" sort="Sieh, Weiva" uniqKey="Sieh W" first="Weiva" last="Sieh">Weiva Sieh</name>
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<name sortKey="Webb, Penelope" sort="Webb, Penelope" uniqKey="Webb P" first="Penelope" last="Webb">Penelope Webb</name>
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<name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name>
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<nlm:aff id="A5">Division of Cancer Epidemiology, German Cancer Research Center</nlm:aff>
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<name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name>
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<name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name>
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<nlm:aff id="A6">Department of Epidemiology, University of California Irvine</nlm:aff>
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<name sortKey="Berchuck, Andrew" sort="Berchuck, Andrew" uniqKey="Berchuck A" first="Andrew" last="Berchuck">Andrew Berchuck</name>
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<nlm:aff id="A7">Department of Obstetrics and Gynecology, Duke University Medical Center</nlm:aff>
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<name sortKey="Brinton, Louise" sort="Brinton, Louise" uniqKey="Brinton L" first="Louise" last="Brinton">Louise Brinton</name>
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<nlm:aff id="A8">Division of Cancer Epidemiology and Genetics, National Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">National Cancer Institute</wicri:noCountry>
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<name sortKey="Cunningham, Julie M" sort="Cunningham, Julie M" uniqKey="Cunningham J" first="Julie M" last="Cunningham">Julie M. Cunningham</name>
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<nlm:aff id="A9">Department of Laboratory Medicine and Pathology, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
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<author>
<name sortKey="Defazio, Anna" sort="Defazio, Anna" uniqKey="Defazio A" first="Anna" last="Defazio">Anna Defazio</name>
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<wicri:noCountry code="subfield">Westmead Millennium Institute</wicri:noCountry>
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<name sortKey="Edwards, Robert P" sort="Edwards, Robert P" uniqKey="Edwards R" first="Robert P" last="Edwards">Robert P. Edwards</name>
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<wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry>
</affiliation>
</author>
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<nlm:aff id="A13">Department of Biomedical Sciences, Cedars-Sinai Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Cedars-Sinai Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Gentry Maharaj, Aleksandra" sort="Gentry Maharaj, Aleksandra" uniqKey="Gentry Maharaj A" first="Aleksandra" last="Gentry-Maharaj">Aleksandra Gentry-Maharaj</name>
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<name sortKey="Goodman, Marc T" sort="Goodman, Marc T" uniqKey="Goodman M" first="Marc T" last="Goodman">Marc T. Goodman</name>
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<nlm:aff id="A13">Department of Biomedical Sciences, Cedars-Sinai Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Cedars-Sinai Medical Center</wicri:noCountry>
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<name sortKey="H Gdall, Estrid" sort="H Gdall, Estrid" uniqKey="H Gdall E" first="Estrid" last="H Gdall">Estrid H Gdall</name>
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<wicri:noCountry code="subfield">Danish Cancer Society Research Center</wicri:noCountry>
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<nlm:aff id="A16">Department of Pathology, Herlev Hospital, University of Copenhagen</nlm:aff>
<wicri:noCountry code="subfield">University of Copenhagen</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Jensen, Allan" sort="Jensen, Allan" uniqKey="Jensen A" first="Allan" last="Jensen">Allan Jensen</name>
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<nlm:aff id="A15">Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center</nlm:aff>
<wicri:noCountry code="subfield">Danish Cancer Society Research Center</wicri:noCountry>
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<name sortKey="Johnatty, Sharon E" sort="Johnatty, Sharon E" uniqKey="Johnatty S" first="Sharon E" last="Johnatty">Sharon E. Johnatty</name>
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<nlm:aff id="A17">Division of Genetics and Public Health, QIMR Berghofer Medical Research Institute</nlm:aff>
<wicri:noCountry code="subfield">QIMR Berghofer Medical Research Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Kiemeney, Lambertus A" sort="Kiemeney, Lambertus A" uniqKey="Kiemeney L" first="Lambertus A" last="Kiemeney">Lambertus A. Kiemeney</name>
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<nlm:aff id="A18">Department of Health Evidence, Radboud University Medical Centre</nlm:aff>
<wicri:noCountry code="subfield">Radboud University Medical Centre</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Kjaer, Susanne K" sort="Kjaer, Susanne K" uniqKey="Kjaer S" first="Susanne K" last="Kjaer">Susanne K. Kjaer</name>
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<nlm:aff id="A19">Department of Gynecology, Rigshospitalet, University of Copenhagen</nlm:aff>
<wicri:noCountry code="subfield">University of Copenhagen</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Larson, Melissa C" sort="Larson, Melissa C" uniqKey="Larson M" first="Melissa C" last="Larson">Melissa C. Larson</name>
<affiliation>
<nlm:aff id="A20">Department of Health Science Research, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Lurie, Galina" sort="Lurie, Galina" uniqKey="Lurie G" first="Galina" last="Lurie">Galina Lurie</name>
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<nlm:aff id="A21">Cancer Epidemiology Program, University of Hawaii Cancer Center</nlm:aff>
<wicri:noCountry code="subfield">University of Hawaii Cancer Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Massuger, Leon" sort="Massuger, Leon" uniqKey="Massuger L" first="Leon" last="Massuger">Leon Massuger</name>
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<nlm:aff id="A22">Department of Obstetrics & Gynecology, Radboud University Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Radboud University Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Menon, Usha" sort="Menon, Usha" uniqKey="Menon U" first="Usha" last="Menon">Usha Menon</name>
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<nlm:aff id="A14">Women's Cancer, Institute for Women's Health, University College London</nlm:aff>
<country>Royaume-Uni</country>
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<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
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<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
<author>
<name sortKey="Modugno, Francesmary" sort="Modugno, Francesmary" uniqKey="Modugno F" first="Francesmary" last="Modugno">Francesmary Modugno</name>
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<nlm:aff id="A12">Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A23">Department of Epidemiology, University of Pittsburgh</nlm:aff>
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<settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
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<author>
<name sortKey="Moysich, Kirsten B" sort="Moysich, Kirsten B" uniqKey="Moysich K" first="Kirsten B" last="Moysich">Kirsten B. Moysich</name>
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<nlm:aff id="A24">Department of Cancer Prevention and Control, Roswell Park Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">Roswell Park Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Ness, Roberta B" sort="Ness, Roberta B" uniqKey="Ness R" first="Roberta B" last="Ness">Roberta B. Ness</name>
<affiliation>
<nlm:aff id="A25">School of Public Health, The University of Texas School</nlm:aff>
<wicri:noCountry code="subfield">The University of Texas School</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Pike, Malcolm C" sort="Pike, Malcolm C" uniqKey="Pike M" first="Malcolm C" last="Pike">Malcolm C. Pike</name>
<affiliation>
<nlm:aff id="A26">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center</nlm:aff>
<wicri:noCountry code="subfield">Memorial Sloan-Kettering Cancer Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Ramus, Susan J" sort="Ramus, Susan J" uniqKey="Ramus S" first="Susan J" last="Ramus">Susan J. Ramus</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Rossing, Mary Anne" sort="Rossing, Mary Anne" uniqKey="Rossing M" first="Mary Anne" last="Rossing">Mary Anne Rossing</name>
<affiliation>
<nlm:aff id="A28">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center</nlm:aff>
<wicri:noCountry code="subfield">Fred Hutchinson Cancer Research Center</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A29">Department of Epidemiology, University of Washington</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author>
<name sortKey="Rothstein, Joseph" sort="Rothstein, Joseph" uniqKey="Rothstein J" first="Joseph" last="Rothstein">Joseph Rothstein</name>
<affiliation>
<nlm:aff id="A3">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">Stanford University School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Song, Honglin" sort="Song, Honglin" uniqKey="Song H" first="Honglin" last="Song">Honglin Song</name>
<affiliation wicri:level="4">
<nlm:aff id="A2">Department of Oncology, University of Cambridge, Strangeways Research Laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Thompson, Pamela J" sort="Thompson, Pamela J" uniqKey="Thompson P" first="Pamela J" last="Thompson">Pamela J. Thompson</name>
<affiliation>
<nlm:aff id="A13">Department of Biomedical Sciences, Cedars-Sinai Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Cedars-Sinai Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Van Den Berg, David J" sort="Van Den Berg, David J" uniqKey="Van Den Berg D" first="David J." last="Van Den Berg">David J. Van Den Berg</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Vierkant, Robert A" sort="Vierkant, Robert A" uniqKey="Vierkant R" first="Robert A" last="Vierkant">Robert A. Vierkant</name>
<affiliation>
<nlm:aff id="A20">Department of Health Science Research, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Wang Gohrke, Shan" sort="Wang Gohrke, Shan" uniqKey="Wang Gohrke S" first="Shan" last="Wang-Gohrke">Shan Wang-Gohrke</name>
<affiliation wicri:level="4">
<nlm:aff id="A30">Department of Obstetrics and Gynecology, University of Ulm</nlm:aff>
<country>Allemagne</country>
<placeName>
<settlement type="city">Ulm</settlement>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
</placeName>
<orgName type="university">Université d'Ulm</orgName>
</affiliation>
</author>
<author>
<name sortKey="Wentzensen, Nicolas" sort="Wentzensen, Nicolas" uniqKey="Wentzensen N" first="Nicolas" last="Wentzensen">Nicolas Wentzensen</name>
<affiliation>
<nlm:aff id="A8">Division of Cancer Epidemiology and Genetics, National Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">National Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Whittemore, Alice S" sort="Whittemore, Alice S" uniqKey="Whittemore A" first="Alice S" last="Whittemore">Alice S. Whittemore</name>
<affiliation>
<nlm:aff id="A3">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">Stanford University School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Wilkens, Lynne R" sort="Wilkens, Lynne R" uniqKey="Wilkens L" first="Lynne R" last="Wilkens">Lynne R. Wilkens</name>
<affiliation>
<nlm:aff id="A21">Cancer Epidemiology Program, University of Hawaii Cancer Center</nlm:aff>
<wicri:noCountry code="subfield">University of Hawaii Cancer Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H" last="Wu">Anna H. Wu</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Yang, Hannah" sort="Yang, Hannah" uniqKey="Yang H" first="Hannah" last="Yang">Hannah Yang</name>
<affiliation>
<nlm:aff id="A8">Division of Cancer Epidemiology and Genetics, National Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">National Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Pearce, Celeste L" sort="Pearce, Celeste L" uniqKey="Pearce C" first="Celeste L" last="Pearce">Celeste L. Pearce</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
<affiliation>
<nlm:aff id="A31">Department of Epidemiology, University of Michigan</nlm:aff>
<wicri:noCountry code="subfield">University of Michigan</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Schildkraut, Joellen M" sort="Schildkraut, Joellen M" uniqKey="Schildkraut J" first="Joellen M" last="Schildkraut">Joellen M. Schildkraut</name>
<affiliation>
<nlm:aff id="A32">Department of Public Health Sciences, University of Virginia</nlm:aff>
<wicri:noCountry code="subfield">University of Virginia</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Pharoah, Paul" sort="Pharoah, Paul" uniqKey="Pharoah P" first="Paul" last="Pharoah">Paul Pharoah</name>
<affiliation wicri:level="4">
<nlm:aff id="A2">Department of Oncology, University of Cambridge, Strangeways Research Laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A33">Dept of Public Health and Primary Care, University of Cambridge, Strangeways Research laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
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<name sortKey="Goode, Ellen L" sort="Goode, Ellen L" uniqKey="Goode E" first="Ellen L" last="Goode">Ellen L. Goode</name>
<affiliation>
<nlm:aff id="A20">Department of Health Science Research, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Fridley, Brooke L" sort="Fridley, Brooke L" uniqKey="Fridley B" first="Brooke L" last="Fridley">Brooke L. Fridley</name>
<affiliation>
<nlm:aff id="A1">Department of Biostatistics, University of Kansas Medical Center</nlm:aff>
<wicri:noCountry code="subfield">University of Kansas Medical Center</wicri:noCountry>
</affiliation>
</author>
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<title xml:lang="en" level="a" type="main">Assessment of multifactor gene-environment interactions and ovarian cancer risk: Candidate genes, obesity, and hormone-related risk factors</title>
<author>
<name sortKey="Usset, Joseph L" sort="Usset, Joseph L" uniqKey="Usset J" first="Joseph L" last="Usset">Joseph L. Usset</name>
<affiliation>
<nlm:aff id="A1">Department of Biostatistics, University of Kansas Medical Center</nlm:aff>
<wicri:noCountry code="subfield">University of Kansas Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Raghavan, Rama" sort="Raghavan, Rama" uniqKey="Raghavan R" first="Rama" last="Raghavan">Rama Raghavan</name>
<affiliation>
<nlm:aff id="A1">Department of Biostatistics, University of Kansas Medical Center</nlm:aff>
<wicri:noCountry code="subfield">University of Kansas Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Tyrer, Jonathan P" sort="Tyrer, Jonathan P" uniqKey="Tyrer J" first="Jonathan P" last="Tyrer">Jonathan P. Tyrer</name>
<affiliation wicri:level="4">
<nlm:aff id="A2">Department of Oncology, University of Cambridge, Strangeways Research Laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mcguire, Valerie" sort="Mcguire, Valerie" uniqKey="Mcguire V" first="Valerie" last="Mcguire">Valerie Mcguire</name>
<affiliation>
<nlm:aff id="A3">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">Stanford University School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Sieh, Weiva" sort="Sieh, Weiva" uniqKey="Sieh W" first="Weiva" last="Sieh">Weiva Sieh</name>
<affiliation>
<nlm:aff id="A3">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">Stanford University School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Webb, Penelope" sort="Webb, Penelope" uniqKey="Webb P" first="Penelope" last="Webb">Penelope Webb</name>
<affiliation>
<nlm:aff id="A4">Population Health Department, QIMR Berghofer Medical Research Institute</nlm:aff>
<wicri:noCountry code="subfield">QIMR Berghofer Medical Research Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name>
<affiliation>
<nlm:aff id="A5">Division of Cancer Epidemiology, German Cancer Research Center</nlm:aff>
<wicri:noCountry code="subfield">German Cancer Research Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name>
<affiliation>
<nlm:aff id="A5">Division of Cancer Epidemiology, German Cancer Research Center</nlm:aff>
<wicri:noCountry code="subfield">German Cancer Research Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name>
<affiliation>
<nlm:aff id="A6">Department of Epidemiology, University of California Irvine</nlm:aff>
<wicri:noCountry code="subfield">University of California Irvine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Berchuck, Andrew" sort="Berchuck, Andrew" uniqKey="Berchuck A" first="Andrew" last="Berchuck">Andrew Berchuck</name>
<affiliation>
<nlm:aff id="A7">Department of Obstetrics and Gynecology, Duke University Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Duke University Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Brinton, Louise" sort="Brinton, Louise" uniqKey="Brinton L" first="Louise" last="Brinton">Louise Brinton</name>
<affiliation>
<nlm:aff id="A8">Division of Cancer Epidemiology and Genetics, National Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">National Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Cunningham, Julie M" sort="Cunningham, Julie M" uniqKey="Cunningham J" first="Julie M" last="Cunningham">Julie M. Cunningham</name>
<affiliation>
<nlm:aff id="A9">Department of Laboratory Medicine and Pathology, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Defazio, Anna" sort="Defazio, Anna" uniqKey="Defazio A" first="Anna" last="Defazio">Anna Defazio</name>
<affiliation>
<nlm:aff id="A10">Discipline of Obstetrics, Gynecology and Neonatology, University of Sydney, Westmead Institute for Cancer Research, Westmead Millennium Institute</nlm:aff>
<wicri:noCountry code="subfield">Westmead Millennium Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Doherty, Jennifer A" sort="Doherty, Jennifer A" uniqKey="Doherty J" first="Jennifer A" last="Doherty">Jennifer A. Doherty</name>
<affiliation>
<nlm:aff id="A11">Department of Epidemiology, Geisel School of Medicine, Dartmouth</nlm:aff>
<wicri:noCountry code="subfield">Dartmouth</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Edwards, Robert P" sort="Edwards, Robert P" uniqKey="Edwards R" first="Robert P" last="Edwards">Robert P. Edwards</name>
<affiliation>
<nlm:aff id="A12">Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A" last="Gayther">Simon A. Gayther</name>
<affiliation>
<nlm:aff id="A13">Department of Biomedical Sciences, Cedars-Sinai Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Cedars-Sinai Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Gentry Maharaj, Aleksandra" sort="Gentry Maharaj, Aleksandra" uniqKey="Gentry Maharaj A" first="Aleksandra" last="Gentry-Maharaj">Aleksandra Gentry-Maharaj</name>
<affiliation wicri:level="4">
<nlm:aff id="A14">Women's Cancer, Institute for Women's Health, University College London</nlm:aff>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
<author>
<name sortKey="Goodman, Marc T" sort="Goodman, Marc T" uniqKey="Goodman M" first="Marc T" last="Goodman">Marc T. Goodman</name>
<affiliation>
<nlm:aff id="A13">Department of Biomedical Sciences, Cedars-Sinai Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Cedars-Sinai Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="H Gdall, Estrid" sort="H Gdall, Estrid" uniqKey="H Gdall E" first="Estrid" last="H Gdall">Estrid H Gdall</name>
<affiliation>
<nlm:aff id="A15">Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center</nlm:aff>
<wicri:noCountry code="subfield">Danish Cancer Society Research Center</wicri:noCountry>
</affiliation>
<affiliation>
<nlm:aff id="A16">Department of Pathology, Herlev Hospital, University of Copenhagen</nlm:aff>
<wicri:noCountry code="subfield">University of Copenhagen</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Jensen, Allan" sort="Jensen, Allan" uniqKey="Jensen A" first="Allan" last="Jensen">Allan Jensen</name>
<affiliation>
<nlm:aff id="A15">Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center</nlm:aff>
<wicri:noCountry code="subfield">Danish Cancer Society Research Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Johnatty, Sharon E" sort="Johnatty, Sharon E" uniqKey="Johnatty S" first="Sharon E" last="Johnatty">Sharon E. Johnatty</name>
<affiliation>
<nlm:aff id="A17">Division of Genetics and Public Health, QIMR Berghofer Medical Research Institute</nlm:aff>
<wicri:noCountry code="subfield">QIMR Berghofer Medical Research Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Kiemeney, Lambertus A" sort="Kiemeney, Lambertus A" uniqKey="Kiemeney L" first="Lambertus A" last="Kiemeney">Lambertus A. Kiemeney</name>
<affiliation>
<nlm:aff id="A18">Department of Health Evidence, Radboud University Medical Centre</nlm:aff>
<wicri:noCountry code="subfield">Radboud University Medical Centre</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Kjaer, Susanne K" sort="Kjaer, Susanne K" uniqKey="Kjaer S" first="Susanne K" last="Kjaer">Susanne K. Kjaer</name>
<affiliation>
<nlm:aff id="A19">Department of Gynecology, Rigshospitalet, University of Copenhagen</nlm:aff>
<wicri:noCountry code="subfield">University of Copenhagen</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Larson, Melissa C" sort="Larson, Melissa C" uniqKey="Larson M" first="Melissa C" last="Larson">Melissa C. Larson</name>
<affiliation>
<nlm:aff id="A20">Department of Health Science Research, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Lurie, Galina" sort="Lurie, Galina" uniqKey="Lurie G" first="Galina" last="Lurie">Galina Lurie</name>
<affiliation>
<nlm:aff id="A21">Cancer Epidemiology Program, University of Hawaii Cancer Center</nlm:aff>
<wicri:noCountry code="subfield">University of Hawaii Cancer Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Massuger, Leon" sort="Massuger, Leon" uniqKey="Massuger L" first="Leon" last="Massuger">Leon Massuger</name>
<affiliation>
<nlm:aff id="A22">Department of Obstetrics & Gynecology, Radboud University Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Radboud University Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Menon, Usha" sort="Menon, Usha" uniqKey="Menon U" first="Usha" last="Menon">Usha Menon</name>
<affiliation wicri:level="4">
<nlm:aff id="A14">Women's Cancer, Institute for Women's Health, University College London</nlm:aff>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
<author>
<name sortKey="Modugno, Francesmary" sort="Modugno, Francesmary" uniqKey="Modugno F" first="Francesmary" last="Modugno">Francesmary Modugno</name>
<affiliation>
<nlm:aff id="A12">Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">University of Pittsburgh School of Medicine</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A23">Department of Epidemiology, University of Pittsburgh</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author>
<name sortKey="Moysich, Kirsten B" sort="Moysich, Kirsten B" uniqKey="Moysich K" first="Kirsten B" last="Moysich">Kirsten B. Moysich</name>
<affiliation>
<nlm:aff id="A24">Department of Cancer Prevention and Control, Roswell Park Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">Roswell Park Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Ness, Roberta B" sort="Ness, Roberta B" uniqKey="Ness R" first="Roberta B" last="Ness">Roberta B. Ness</name>
<affiliation>
<nlm:aff id="A25">School of Public Health, The University of Texas School</nlm:aff>
<wicri:noCountry code="subfield">The University of Texas School</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Pike, Malcolm C" sort="Pike, Malcolm C" uniqKey="Pike M" first="Malcolm C" last="Pike">Malcolm C. Pike</name>
<affiliation>
<nlm:aff id="A26">Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center</nlm:aff>
<wicri:noCountry code="subfield">Memorial Sloan-Kettering Cancer Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Ramus, Susan J" sort="Ramus, Susan J" uniqKey="Ramus S" first="Susan J" last="Ramus">Susan J. Ramus</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Rossing, Mary Anne" sort="Rossing, Mary Anne" uniqKey="Rossing M" first="Mary Anne" last="Rossing">Mary Anne Rossing</name>
<affiliation>
<nlm:aff id="A28">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center</nlm:aff>
<wicri:noCountry code="subfield">Fred Hutchinson Cancer Research Center</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A29">Department of Epidemiology, University of Washington</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author>
<name sortKey="Rothstein, Joseph" sort="Rothstein, Joseph" uniqKey="Rothstein J" first="Joseph" last="Rothstein">Joseph Rothstein</name>
<affiliation>
<nlm:aff id="A3">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">Stanford University School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Song, Honglin" sort="Song, Honglin" uniqKey="Song H" first="Honglin" last="Song">Honglin Song</name>
<affiliation wicri:level="4">
<nlm:aff id="A2">Department of Oncology, University of Cambridge, Strangeways Research Laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Thompson, Pamela J" sort="Thompson, Pamela J" uniqKey="Thompson P" first="Pamela J" last="Thompson">Pamela J. Thompson</name>
<affiliation>
<nlm:aff id="A13">Department of Biomedical Sciences, Cedars-Sinai Medical Center</nlm:aff>
<wicri:noCountry code="subfield">Cedars-Sinai Medical Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Van Den Berg, David J" sort="Van Den Berg, David J" uniqKey="Van Den Berg D" first="David J." last="Van Den Berg">David J. Van Den Berg</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Vierkant, Robert A" sort="Vierkant, Robert A" uniqKey="Vierkant R" first="Robert A" last="Vierkant">Robert A. Vierkant</name>
<affiliation>
<nlm:aff id="A20">Department of Health Science Research, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Wang Gohrke, Shan" sort="Wang Gohrke, Shan" uniqKey="Wang Gohrke S" first="Shan" last="Wang-Gohrke">Shan Wang-Gohrke</name>
<affiliation wicri:level="4">
<nlm:aff id="A30">Department of Obstetrics and Gynecology, University of Ulm</nlm:aff>
<country>Allemagne</country>
<placeName>
<settlement type="city">Ulm</settlement>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Tübingen</region>
</placeName>
<orgName type="university">Université d'Ulm</orgName>
</affiliation>
</author>
<author>
<name sortKey="Wentzensen, Nicolas" sort="Wentzensen, Nicolas" uniqKey="Wentzensen N" first="Nicolas" last="Wentzensen">Nicolas Wentzensen</name>
<affiliation>
<nlm:aff id="A8">Division of Cancer Epidemiology and Genetics, National Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">National Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Whittemore, Alice S" sort="Whittemore, Alice S" uniqKey="Whittemore A" first="Alice S" last="Whittemore">Alice S. Whittemore</name>
<affiliation>
<nlm:aff id="A3">Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine</nlm:aff>
<wicri:noCountry code="subfield">Stanford University School of Medicine</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Wilkens, Lynne R" sort="Wilkens, Lynne R" uniqKey="Wilkens L" first="Lynne R" last="Wilkens">Lynne R. Wilkens</name>
<affiliation>
<nlm:aff id="A21">Cancer Epidemiology Program, University of Hawaii Cancer Center</nlm:aff>
<wicri:noCountry code="subfield">University of Hawaii Cancer Center</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H" last="Wu">Anna H. Wu</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Yang, Hannah" sort="Yang, Hannah" uniqKey="Yang H" first="Hannah" last="Yang">Hannah Yang</name>
<affiliation>
<nlm:aff id="A8">Division of Cancer Epidemiology and Genetics, National Cancer Institute</nlm:aff>
<wicri:noCountry code="subfield">National Cancer Institute</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Pearce, Celeste L" sort="Pearce, Celeste L" uniqKey="Pearce C" first="Celeste L" last="Pearce">Celeste L. Pearce</name>
<affiliation wicri:level="4">
<nlm:aff id="A27">Department of Preventive Medicine, University of Southern California</nlm:aff>
<country>États-Unis</country>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
<affiliation>
<nlm:aff id="A31">Department of Epidemiology, University of Michigan</nlm:aff>
<wicri:noCountry code="subfield">University of Michigan</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Schildkraut, Joellen M" sort="Schildkraut, Joellen M" uniqKey="Schildkraut J" first="Joellen M" last="Schildkraut">Joellen M. Schildkraut</name>
<affiliation>
<nlm:aff id="A32">Department of Public Health Sciences, University of Virginia</nlm:aff>
<wicri:noCountry code="subfield">University of Virginia</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Pharoah, Paul" sort="Pharoah, Paul" uniqKey="Pharoah P" first="Paul" last="Pharoah">Paul Pharoah</name>
<affiliation wicri:level="4">
<nlm:aff id="A2">Department of Oncology, University of Cambridge, Strangeways Research Laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A33">Dept of Public Health and Primary Care, University of Cambridge, Strangeways Research laboratory</nlm:aff>
<orgName type="university">Université de Cambridge</orgName>
<country>Royaume-Uni</country>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Goode, Ellen L" sort="Goode, Ellen L" uniqKey="Goode E" first="Ellen L" last="Goode">Ellen L. Goode</name>
<affiliation>
<nlm:aff id="A20">Department of Health Science Research, Mayo Clinic</nlm:aff>
<wicri:noCountry code="subfield">Mayo Clinic</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Fridley, Brooke L" sort="Fridley, Brooke L" uniqKey="Fridley B" first="Brooke L" last="Fridley">Brooke L. Fridley</name>
<affiliation>
<nlm:aff id="A1">Department of Biostatistics, University of Kansas Medical Center</nlm:aff>
<wicri:noCountry code="subfield">University of Kansas Medical Center</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology</title>
<idno type="ISSN">1055-9965</idno>
<idno type="eISSN">1538-7755</idno>
<imprint>
<date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Background</title>
<p id="P1">Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure, and elevated estrogen levels are associated with obesity in post-menopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">We considered interactions between 11,441 single nucleotide polymorphisms (SNPs) within 80 candidate genes related to hormone biosynthesis & metabolism and insulin-like growth factors with six hormone-related factors: oral contraceptive use; parity; endometriosis; tubal ligation; hormone replacement therapy; and estrogen use; and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype specific analyses were also completed.</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">SNPs in the following candidate genes showed notable interaction:
<italic>IGF1R</italic>
(rs41497346, estrogen plus progesterone hormone therapy, histology = all, p = 4.9×10
<sup>−6</sup>
) and
<italic>ESR1</italic>
(rs12661437, endometriosis, histology = all, p = 1.5×10
<sup>−5</sup>
). The most notable obesity - gene - hormone risk factor interaction was within
<italic>INSR</italic>
(rs113759408, parity, histology = endometrioid, p = 8.8×10
<sup>−6</sup>
).</p>
</sec>
<sec id="S4">
<title>Conclusions</title>
<p id="P4">We have demonstrated the feasibility of assessing multi-factor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for
<italic>ESR1, CYP11A1, IGF1R, CYP11B1, INSR</italic>
, and
<italic>IGFBP2</italic>
. Future work is needed to develop powerful statistical methods able to detect these complex interactions.</p>
</sec>
<sec id="S5">
<title>Impact</title>
<p id="P5">Assessment of multifactor interaction is feasible, and, here, suggest that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility.</p>
</sec>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Bade-Wurtemberg</li>
<li>Californie</li>
<li>District de Tübingen</li>
<li>Grand Londres</li>
<li>Pennsylvanie</li>
<li>Washington (État)</li>
</region>
<settlement>
<li>Cambridge</li>
<li>Londres</li>
<li>Los Angeles</li>
<li>Pittsburgh</li>
<li>Seattle</li>
<li>Ulm</li>
</settlement>
<orgName>
<li>University College de Londres</li>
<li>Université d'Ulm</li>
<li>Université de Californie du Sud</li>
<li>Université de Cambridge</li>
<li>Université de Pittsburgh</li>
<li>Université de Washington</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Anton Culver, Hoda" sort="Anton Culver, Hoda" uniqKey="Anton Culver H" first="Hoda" last="Anton-Culver">Hoda Anton-Culver</name>
<name sortKey="Berchuck, Andrew" sort="Berchuck, Andrew" uniqKey="Berchuck A" first="Andrew" last="Berchuck">Andrew Berchuck</name>
<name sortKey="Brinton, Louise" sort="Brinton, Louise" uniqKey="Brinton L" first="Louise" last="Brinton">Louise Brinton</name>
<name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name>
<name sortKey="Cunningham, Julie M" sort="Cunningham, Julie M" uniqKey="Cunningham J" first="Julie M" last="Cunningham">Julie M. Cunningham</name>
<name sortKey="Defazio, Anna" sort="Defazio, Anna" uniqKey="Defazio A" first="Anna" last="Defazio">Anna Defazio</name>
<name sortKey="Doherty, Jennifer A" sort="Doherty, Jennifer A" uniqKey="Doherty J" first="Jennifer A" last="Doherty">Jennifer A. Doherty</name>
<name sortKey="Edwards, Robert P" sort="Edwards, Robert P" uniqKey="Edwards R" first="Robert P" last="Edwards">Robert P. Edwards</name>
<name sortKey="Fridley, Brooke L" sort="Fridley, Brooke L" uniqKey="Fridley B" first="Brooke L" last="Fridley">Brooke L. Fridley</name>
<name sortKey="Gayther, Simon A" sort="Gayther, Simon A" uniqKey="Gayther S" first="Simon A" last="Gayther">Simon A. Gayther</name>
<name sortKey="Goode, Ellen L" sort="Goode, Ellen L" uniqKey="Goode E" first="Ellen L" last="Goode">Ellen L. Goode</name>
<name sortKey="Goodman, Marc T" sort="Goodman, Marc T" uniqKey="Goodman M" first="Marc T" last="Goodman">Marc T. Goodman</name>
<name sortKey="H Gdall, Estrid" sort="H Gdall, Estrid" uniqKey="H Gdall E" first="Estrid" last="H Gdall">Estrid H Gdall</name>
<name sortKey="Jensen, Allan" sort="Jensen, Allan" uniqKey="Jensen A" first="Allan" last="Jensen">Allan Jensen</name>
<name sortKey="Johnatty, Sharon E" sort="Johnatty, Sharon E" uniqKey="Johnatty S" first="Sharon E" last="Johnatty">Sharon E. Johnatty</name>
<name sortKey="Kiemeney, Lambertus A" sort="Kiemeney, Lambertus A" uniqKey="Kiemeney L" first="Lambertus A" last="Kiemeney">Lambertus A. Kiemeney</name>
<name sortKey="Kjaer, Susanne K" sort="Kjaer, Susanne K" uniqKey="Kjaer S" first="Susanne K" last="Kjaer">Susanne K. Kjaer</name>
<name sortKey="Larson, Melissa C" sort="Larson, Melissa C" uniqKey="Larson M" first="Melissa C" last="Larson">Melissa C. Larson</name>
<name sortKey="Lurie, Galina" sort="Lurie, Galina" uniqKey="Lurie G" first="Galina" last="Lurie">Galina Lurie</name>
<name sortKey="Massuger, Leon" sort="Massuger, Leon" uniqKey="Massuger L" first="Leon" last="Massuger">Leon Massuger</name>
<name sortKey="Mcguire, Valerie" sort="Mcguire, Valerie" uniqKey="Mcguire V" first="Valerie" last="Mcguire">Valerie Mcguire</name>
<name sortKey="Moysich, Kirsten B" sort="Moysich, Kirsten B" uniqKey="Moysich K" first="Kirsten B" last="Moysich">Kirsten B. Moysich</name>
<name sortKey="Ness, Roberta B" sort="Ness, Roberta B" uniqKey="Ness R" first="Roberta B" last="Ness">Roberta B. Ness</name>
<name sortKey="Pike, Malcolm C" sort="Pike, Malcolm C" uniqKey="Pike M" first="Malcolm C" last="Pike">Malcolm C. Pike</name>
<name sortKey="Raghavan, Rama" sort="Raghavan, Rama" uniqKey="Raghavan R" first="Rama" last="Raghavan">Rama Raghavan</name>
<name sortKey="Rothstein, Joseph" sort="Rothstein, Joseph" uniqKey="Rothstein J" first="Joseph" last="Rothstein">Joseph Rothstein</name>
<name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name>
<name sortKey="Schildkraut, Joellen M" sort="Schildkraut, Joellen M" uniqKey="Schildkraut J" first="Joellen M" last="Schildkraut">Joellen M. Schildkraut</name>
<name sortKey="Sieh, Weiva" sort="Sieh, Weiva" uniqKey="Sieh W" first="Weiva" last="Sieh">Weiva Sieh</name>
<name sortKey="Thompson, Pamela J" sort="Thompson, Pamela J" uniqKey="Thompson P" first="Pamela J" last="Thompson">Pamela J. Thompson</name>
<name sortKey="Usset, Joseph L" sort="Usset, Joseph L" uniqKey="Usset J" first="Joseph L" last="Usset">Joseph L. Usset</name>
<name sortKey="Vierkant, Robert A" sort="Vierkant, Robert A" uniqKey="Vierkant R" first="Robert A" last="Vierkant">Robert A. Vierkant</name>
<name sortKey="Webb, Penelope" sort="Webb, Penelope" uniqKey="Webb P" first="Penelope" last="Webb">Penelope Webb</name>
<name sortKey="Wentzensen, Nicolas" sort="Wentzensen, Nicolas" uniqKey="Wentzensen N" first="Nicolas" last="Wentzensen">Nicolas Wentzensen</name>
<name sortKey="Whittemore, Alice S" sort="Whittemore, Alice S" uniqKey="Whittemore A" first="Alice S" last="Whittemore">Alice S. Whittemore</name>
<name sortKey="Wilkens, Lynne R" sort="Wilkens, Lynne R" uniqKey="Wilkens L" first="Lynne R" last="Wilkens">Lynne R. Wilkens</name>
<name sortKey="Yang, Hannah" sort="Yang, Hannah" uniqKey="Yang H" first="Hannah" last="Yang">Hannah Yang</name>
</noCountry>
<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Tyrer, Jonathan P" sort="Tyrer, Jonathan P" uniqKey="Tyrer J" first="Jonathan P" last="Tyrer">Jonathan P. Tyrer</name>
</region>
<name sortKey="Gentry Maharaj, Aleksandra" sort="Gentry Maharaj, Aleksandra" uniqKey="Gentry Maharaj A" first="Aleksandra" last="Gentry-Maharaj">Aleksandra Gentry-Maharaj</name>
<name sortKey="Menon, Usha" sort="Menon, Usha" uniqKey="Menon U" first="Usha" last="Menon">Usha Menon</name>
<name sortKey="Pharoah, Paul" sort="Pharoah, Paul" uniqKey="Pharoah P" first="Paul" last="Pharoah">Paul Pharoah</name>
<name sortKey="Pharoah, Paul" sort="Pharoah, Paul" uniqKey="Pharoah P" first="Paul" last="Pharoah">Paul Pharoah</name>
<name sortKey="Song, Honglin" sort="Song, Honglin" uniqKey="Song H" first="Honglin" last="Song">Honglin Song</name>
</country>
<country name="États-Unis">
<region name="Pennsylvanie">
<name sortKey="Modugno, Francesmary" sort="Modugno, Francesmary" uniqKey="Modugno F" first="Francesmary" last="Modugno">Francesmary Modugno</name>
</region>
<name sortKey="Pearce, Celeste L" sort="Pearce, Celeste L" uniqKey="Pearce C" first="Celeste L" last="Pearce">Celeste L. Pearce</name>
<name sortKey="Ramus, Susan J" sort="Ramus, Susan J" uniqKey="Ramus S" first="Susan J" last="Ramus">Susan J. Ramus</name>
<name sortKey="Rossing, Mary Anne" sort="Rossing, Mary Anne" uniqKey="Rossing M" first="Mary Anne" last="Rossing">Mary Anne Rossing</name>
<name sortKey="Van Den Berg, David J" sort="Van Den Berg, David J" uniqKey="Van Den Berg D" first="David J." last="Van Den Berg">David J. Van Den Berg</name>
<name sortKey="Wu, Anna H" sort="Wu, Anna H" uniqKey="Wu A" first="Anna H" last="Wu">Anna H. Wu</name>
</country>
<country name="Allemagne">
<region name="Bade-Wurtemberg">
<name sortKey="Wang Gohrke, Shan" sort="Wang Gohrke, Shan" uniqKey="Wang Gohrke S" first="Shan" last="Wang-Gohrke">Shan Wang-Gohrke</name>
</region>
</country>
</tree>
</affiliations>
</record>

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