eprintid: 1489584 rev_number: 45 eprint_status: archive userid: 608 dir: disk0/01/48/95/84 datestamp: 2016-05-02 19:11:12 lastmod: 2021-12-13 02:12:05 status_changed: 2016-08-02 16:12:59 type: article metadata_visibility: show creators_name: Usset, JL creators_name: Raghavan, R creators_name: Tyrer, JP creators_name: McGuire, V creators_name: Sieh, W creators_name: Webb, P creators_name: Chang-Claude, J creators_name: Rudolph, A creators_name: Anton-Culver, H creators_name: Berchuck, A creators_name: Brinton, L creators_name: Cunningham, JM creators_name: DeFazio, A creators_name: Doherty, JA creators_name: Edwards, RP creators_name: Gayther, SA creators_name: Gentry-Maharaj, A creators_name: Goodman, MT creators_name: Høgdall, E creators_name: Jensen, A creators_name: Johnatty, SE creators_name: Kiemeney, LA creators_name: Kjaer, SK creators_name: Larson, MC creators_name: Lurie, G creators_name: Massuger, L creators_name: Menon, U creators_name: Modugno, F creators_name: Moysich, KB creators_name: Ness, RB creators_name: Pike, MC creators_name: Ramus, SJ creators_name: Rossing, MA creators_name: Rothstein, J creators_name: Song, H creators_name: Thompson, PJ creators_name: van den Berg, DJ creators_name: Vierkant, RA creators_name: Wang-Gohrke, S creators_name: Wentzensen, N creators_name: Whittemore, AS creators_name: Wilkens, LR creators_name: Wu, AH creators_name: Yang, H creators_name: Pearce, CL creators_name: Schildkraut, JM creators_name: Pharoah, P creators_name: Goode, EL creators_name: Fridley, BL creators_name: Ovarian Cancer Association Consortium, . creators_name: Australian Cancer Study, . title: Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity and Hormone-Related Risk Factors ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 note: Copyright © 2016 American Association for Cancer Research. The published version of record is available at http://dx.doi.org/10.1158/1055-9965.EPI-15-1039 abstract: BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal 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 SNPs within 80 candidate genes related to hormone biosynthesis and 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 multifactor 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, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. date: 2016-05 date_type: published official_url: http://dx.doi.org/10.1158/1055-9965.EPI-15-1039 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1120539 doi: 10.1158/1055-9965.EPI-15-1039 pii: 1055-9965.EPI-15-1039 lyricists_name: Gentry-Maharaj, Aleksandra lyricists_name: Menon, Usha lyricists_id: AGENT07 lyricists_id: UMENO29 full_text_status: public publication: Cancer Epidemiology, Biomarkers & Prevention volume: 25 number: 5 pagerange: 780-790 event_location: United States issn: 1538-7755 citation: Usset, JL; Raghavan, R; Tyrer, JP; McGuire, V; Sieh, W; Webb, P; Chang-Claude, J; ... Australian Cancer Study, .; + view all <#> Usset, JL; Raghavan, R; Tyrer, JP; McGuire, V; Sieh, W; Webb, P; Chang-Claude, J; Rudolph, A; Anton-Culver, H; Berchuck, A; Brinton, L; Cunningham, JM; DeFazio, A; Doherty, JA; Edwards, RP; Gayther, SA; Gentry-Maharaj, A; Goodman, MT; Høgdall, E; Jensen, A; Johnatty, SE; Kiemeney, LA; Kjaer, SK; Larson, MC; Lurie, G; Massuger, L; Menon, U; Modugno, F; Moysich, KB; Ness, RB; Pike, MC; Ramus, SJ; Rossing, MA; Rothstein, J; Song, H; Thompson, PJ; van den Berg, DJ; Vierkant, RA; Wang-Gohrke, S; Wentzensen, N; Whittemore, AS; Wilkens, LR; Wu, AH; Yang, H; Pearce, CL; Schildkraut, JM; Pharoah, P; Goode, EL; Fridley, BL; Ovarian Cancer Association Consortium, .; Australian Cancer Study, .; - view fewer <#> (2016) Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity and Hormone-Related Risk Factors. Cancer Epidemiology, Biomarkers & Prevention , 25 (5) pp. 780-790. 10.1158/1055-9965.EPI-15-1039 <https://doi.org/10.1158/1055-9965.EPI-15-1039>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1489584/1/Usset%20et%20al%20Assessment%20of%20Multifactor%20Gene-Environment%20Interactions%20and%20Ovarian%20Cancer%20Risk%20-%20Candidate%20Genes%20Obesity%20and%20Hormone-Related%20Risk%20Factors%20AAM.pdf