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Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk : A Prospective Study in the EPIC Cohort

Lujan-Barroso, Leila ; Botteri, Edoardo ; Caini, Saverio ; Ljungberg, Börje ; Roswall, Nina ; Tjønneland, Anne ; Bueno-de-Mesquita, Bas ; Gram, Inger T. ; Tumino, Rosario and Kiemeney, Lambertus A. , et al. (2020) In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 29(8). p.1654-1664
Abstract

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status,... (More)

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

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publication status
published
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Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
volume
29
issue
8
pages
11 pages
publisher
American Association for Cancer Research
external identifiers
  • pmid:32467345
  • scopus:85089126979
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-20-0184
language
English
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yes
id
414ebbf7-7696-4a16-8248-04e9efbd576b
date added to LUP
2020-08-18 10:52:51
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2021-06-08 05:59:46
@article{414ebbf7-7696-4a16-8248-04e9efbd576b,
  abstract     = {<p>BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.</p>},
  author       = {Lujan-Barroso, Leila and Botteri, Edoardo and Caini, Saverio and Ljungberg, Börje and Roswall, Nina and Tjønneland, Anne and Bueno-de-Mesquita, Bas and Gram, Inger T. and Tumino, Rosario and Kiemeney, Lambertus A. and Liedberg, Fredrik and Stocks, Tanja and Gunter, Marc J. and Murphy, Neil and Cervenka, Iris and Fournier, Agnès and Kvaskoff, Marina and Häggström, Christel and Overvad, Kim and Lund, Eiliv and Waaseth, Marit and Fortner, Renée Turzanski and Kühn, Tilman and Menéndez, Virginia and Sánchez, Maria Jose and Santiuste, Carmen and Perez-Cornago, Aurora and Zamora-Ros, Raul and Cross, Amanda J. and Trichopoulou, Antonia and Karakatsani, Anna and Peppa, Eleni and Palli, Domenico and Krogh, Vittorio and Sciannameo, Veronica and Mattiello, Amalia and Panico, Salvatore and van Gils, Carla H. and Onland-Moret, N. Charlotte and Barricarte, Aurelio and Amiano, Pilar and Khaw, Kay Tee and Boeing, Heiner and Weiderpass, Elisabete and Duell, Eric J.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {8},
  pages        = {1654--1664},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
  title        = {Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk : A Prospective Study in the EPIC Cohort},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-20-0184},
  doi          = {10.1158/1055-9965.EPI-20-0184},
  volume       = {29},
  year         = {2020},
}