eprintid: 10144864 rev_number: 14 eprint_status: archive userid: 699 dir: disk0/10/14/48/64 datestamp: 2022-05-13 09:01:19 lastmod: 2022-05-13 09:01:19 status_changed: 2022-05-13 09:01:19 type: thesis metadata_visibility: show sword_depositor: 699 creators_name: Williams, Caroline Lucy title: A population-based linkage of administrative data sources to investigate associations between assisted reproductive technology and cancer risk in Great Britain ispublished: unpub divisions: UCL divisions: G25 divisions: D13 divisions: B02 note: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. abstract: Introduction: Exposure of women to supra-physiological hormone levels and exposure of early embryos to artificial environments could increase cancer risks in women who have had assisted reproductive technology (ART) and children born after ART. This study aims to investigate possible associations by linking routinely collected data. Methods: Records of 255,786 ART treated women and 106, 013 ART conceived children in Great Britain (1991-2010) were linked to national registries of England & Wales and of Scotland, and the National Register of Childhood Tumours to obtain cancer outcome status. Observed cancers were compared against age and sex specific expectation, based on national rates. Analyses were stratified for potential moderating, mediating and confounding factors; 95% confidence-intervals, 2-sided P-values and trends were calculated assuming a Poisson distribution. Results: In 2,257,789 person-years of observation in ART treated women with an average follow-up of 8.8 years, no increased risk of corpus uteri (SIR-1.12; 95%CI 0.95-1.30), or invasive breast (SIR-0.96; 0.2-1.00) cancer was detected. An increased risk of ovarian cancer (SIR-1·39; 1·26-1·53), both invasive (SIR-1·40; 1·24-1·58) and borderline (SIR-1·36; 1·15-1·60) was limited to women with endometriosis, nulliparity, or both. There was no increased risk of ovarian tumours in women treated for only male factor or unexplained infertility. In 700,705 person-years of observation in ART conceived children with an average follow-up of 6.6 years, no overall increased risk of childhood cancer was found (SIR-0.98; 0.81-1.19). An excess of hepatoblastoma (SIR-3.64; 1.34-7.93), was likely mediated by low-birthweight (Birthweight<2500g SIR-10.29; 3.34-24.02). Conclusion: Routinely collected national data, linked to investigate cancer outcomes after ART, were largely reassuring, although some specific increases were detected. There was no convincing evidence relating increased risks to ART procedures per se. Average follow-up was 8.8 years for women and 6.6 years for children, therefore longer follow-up is required to confirm impact on lifetime risks. date: 2022-03-28 date_type: published oa_status: green full_text_type: other thesis_class: doctoral_open thesis_award: Ph.D language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1944107 lyricists_name: Williams, Caroline lyricists_id: CLWIL03 actors_name: Williams, Caroline actors_id: CLWIL03 actors_role: owner full_text_status: public pagerange: 1-330 pages: 330 institution: UCL (University College London) department: Institute of Child Health thesis_type: Doctoral citation: Williams, Caroline Lucy; (2022) A population-based linkage of administrative data sources to investigate associations between assisted reproductive technology and cancer risk in Great Britain. Doctoral thesis (Ph.D), UCL (University College London). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10144864/13/Williams_10144864_Thesis_redacted.pdf