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Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study)

Prostate Cancer and Prostatic Diseases volume 25, pages 694–699 (2022)Cite this article

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Abstract

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.

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Acknowledgements

The authors thank Ingrid de Ruiter, MBChB, PhD, for English language support in the preparation of this manuscript. We thank all subjects who participated in the study and all MCC-Spain collaborators.

Data and material availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding

The study was partially funded by the “Acción transversal del cancer”, approved by the Spanish Ministry council on 11 October 2007, by the Instituto de Salud Carlos III-FEDER-a way to build Europe-(PI08/1770, PI08/0533, PI08/1359, pi09/00773, PI09/01286, PI 09/01903, PI09/02078, PI09/01662, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613), by the Fundación Marqués de Valdecilla (api 10/09), by the Junta de Castilla y León (le22a10-2), by the Consejería de Salud of the Junta de Andalucía (2009-s0143), by the Conselleria de Sanitat of the Generalitat Valenciana (ap_061/10), by the Recercaixa (2010acup 00310), by the regional government of the Basque country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission Grants Food-ct-2006-036224-hiwate, by the Spanish Association Against Cancer (AECC) scientific foundation, by the Catalan Government DURSI grant 2014SGR647, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo.

Author information

Author notes

  1. These authors contributed equally: Rocío Barrios-Rodríguez, Esther García-Esquinas.

Authors and Affiliations

  1. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain

    Rocío Barrios-Rodríguez, Esther García-Esquinas, Beatriz Pérez-Gómez, Gemma Castaño-Vinyals, Javier Llorca, Nerea Fernández de Larrea-Baz, Rocío Olmedo-Requena, Juan Alguacil, Guillermo Fernández-Tardón, Pablo Fernández-Navarro, Virginia Lope, Inés Gómez-Acebo, Nuria Aragonés, Manolis Kogevinas, Marina Pollán & José Juan Jiménez-Moleón

  2. Instituto de Investigación Biosanitaria ibs.GRANADA, Complejo Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain

    Rocío Barrios-Rodríguez, Rocío Olmedo-Requena & José Juan Jiménez-Moleón

  3. Universidad de Granada, Departamento de Medicina Preventiva y Salud Pública, Granada, España

    Rocío Barrios-Rodríguez, Rocío Olmedo-Requena & José Juan Jiménez-Moleón

  4. Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid/ IdiPAZ, Madrid, Spain

    Esther García-Esquinas

  5. Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain

    Beatriz Pérez-Gómez, Nerea Fernández de Larrea-Baz, Pablo Fernández-Navarro, Virginia Lope & Marina Pollán

  6. Instituto de Salud Global de Barcelona (ISGlobal), Barcelona, Spain

    Gemma Castaño-Vinyals

  7. Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

    Gemma Castaño-Vinyals & Manolis Kogevinas

  8. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    Gemma Castaño-Vinyals & Manolis Kogevinas

  9. Universidad de Cantabria – IDIVAL, Santander, Spain

    Javier Llorca, Inés Gómez-Acebo & Manolis Kogevinas

  10. Cancer and Public Health Area, FISABIO - Public Health, Valencia, Spain

    Mercedes Vanaclocha-Espi

  11. Centro de Investigación en Salud y Medio Ambiente (CYSMA), Universidad de Huelva, Campus Universitario de El Carmen, Huelva, Spain

    Juan Alguacil

  12. Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, Spain

    Guillermo Fernández-Tardón

  13. Urology Department, Hospital del Mar-IMIM, Autonomous University of Barcelona, Passeig Marítim 25-29, Barcelona, Spain

    Lluís Cecchini

  14. Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain. C/San Martín de Porres, 6, Madrid, Spain

    Nuria Aragonés

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  1. Rocío Barrios-Rodríguez
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Contributions

BP-G, MK, MP and JJJ-M conceptualisation and design of the study; RB-R and EG-E formal analysis of data; NFLB, RO-R, MV-E, GF-T, PF-N, LC, VL and IG-A, data curation; BP-G, GC-V, JL, JA and JJJ-M funding acquisition; GC-V, NA, MK and MP project administration; RB-R, EG-E, BP-G and JJJ-M first draft of this paper. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Beatriz Pérez-Gómez.

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Barrios-Rodríguez, R., García-Esquinas, E., Pérez-Gómez, B. et al. Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study). Prostate Cancer Prostatic Dis 25, 694–699 (2022). https://doi.org/10.1038/s41391-021-00446-w

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