Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study)
Por:
Barrios-Rodríguez R, García-Esquinas E, Pérez-Gómez B, Castaño-Vinyals G, Llorca J, de Larrea-Baz NF, Olmedo-Requena R, Vanaclocha-Espi M, Alguacil J, Fernández-Tardón G, Fernández-Navarro P, Cecchini L, Lope V, Gómez-Acebo I, Aragonés N, Kogevinas M, Pollán M and Jiménez-Moleón JJ
Publicada:
1 abr 2022
Ahead of Print:
1 oct 2021
Resumen:
Background Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. Methods We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. Results Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. Conclusions Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.
Filiaciones:
Barrios-Rodríguez R:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
Universidad de Granada, Departamento de Medicina Preventiva y Salud Pública, Granada, España
García-Esquinas E:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid/ IdiPAZ, Madrid, Spain
Pérez-Gómez B:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.
Castaño-Vinyals G:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Instituto de Salud Global de Barcelona (ISGlobal), Barcelona, Spain
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
Llorca J:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Universidad de Cantabria - IDIVAL, Santander, Spain
de Larrea-Baz NF:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain
Olmedo-Requena R:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
Universidad de Granada, Departamento de Medicina Preventiva y Salud Pública, Granada, España
:
Cancer and Public Health Area, FISABIO - Public Health, Valencia, Spain
Alguacil J:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Centro de Investigación en Salud y Medio Ambiente (CYSMA), Universidad de Huelva, Campus Universitario de El Carmen, Huelva, Spain
Fernández-Tardón G:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, Spain
Fernández-Navarro P:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain
Cecchini L:
Urology Department, Hospital del Mar-IMIM, Autonomous University of Barcelona, Passeig Marítim 25-29, Barcelona, Spain
Lope V:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain
Gómez-Acebo I:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Universidad de Cantabria - IDIVAL, Santander, Spain
Aragonés N:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain. C/San Martín de Porres, 6, Madrid, Spain
Kogevinas M:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
Universidad de Cantabria - IDIVAL, Santander, Spain
Pollán M:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain
Jiménez-Moleón JJ:
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
Universidad de Granada, Departamento de Medicina Preventiva y Salud Pública, Granada, España
Green Accepted
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